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1.
J Neonatal Perinatal Med ; 17(1): 7-11, 2024.
Article in English | MEDLINE | ID: mdl-38393925

ABSTRACT

BACKGROUND: Persistent pulmonary hypertension of the neonate (PPHN) is a serious disorder. The long pentraxin 3 (PTX3) plays an important role in angiogenesis, cell proliferation, tissue repair and cell regulation. The present study aims to assess the diagnostic and clinical value of PTX3 in PPHN. METHODS: The present case-control 60 full-term neonates diagnosed with PPHN by echocardiography within 72 hours of birth. In addition, there were 30 age and sex-matched healthy neonates who served as controls. All participants were subjected to careful history taking and complete clinical examination, Laboratory investigations included complete blood count, C-reactive protein (CRP), blood culture and PTX3 level. Radiological investigations included plain X- ray and two-dimensional transthoracic echocardiography (TTE). RESULTS: Comparison between patients and controls revealed that patients had significantly higher CRP (6.12±2.18 versus 3.69±1.25 mg/dl, p < 0.001) and PTX3 levels (2.07±0.67 versus 0.96±0.21, p < 0.001) when compared with controls. Patients with associated PDA had significantly higher PTX3 levels when compared with patients without (2.58±0.5 versus 2.02±0.51 ng/ml, p = 0.002). Also, patients with associated PFO had significantly higher PTX3 levels when compared with patients without (2.12±1.05 versus 2.05±0.46, p = 0.002). ROC curve analysis identified good performance of CRP and PTX3 levels in diagnosis of PPHN with PTX3 showing better performance. CONCLUSIONS: There is a significant association between serum PTX3 levels and PPHN particularly those with associated PDA or PFO.


Subject(s)
C-Reactive Protein , Hypertension, Pulmonary , Humans , Infant, Newborn , Biomarkers , C-Reactive Protein/metabolism , Case-Control Studies , Hypertension, Pulmonary/diagnosis , ROC Curve , Serum Amyloid P-Component/metabolism , Male , Female
2.
Article in English | MEDLINE | ID: mdl-37817658

ABSTRACT

A diabetic wound is one of the major complications arising from hyperglycemia, neuropathy, and oxidative stress in diabetic patients. Finding effective treatments for diabetic wounds has been difficult owing to the complex pathophysiology of diabetic wound environments. Chronic wounds are notoriously difficult to treat with conventional wound care methods. In recent years, polyphenols found in plants have received much interest as a potential treatment for diabetic wounds. Their key benefits are their safety and the fact that they act through many molecular routes to treat diabetic wounds. However, problems with their formulation development, including lipophilicity, light sensitivity, limited membrane permeability, rapid systemic elimination, and enzymatic degradation, prevented them from gaining clinical attention. This article highlights and discusses the mechanism of polyphenols and various polyphenol-based drug delivery systems used till now to treat diabetic wounds. The consideration that should be taken in polyphenols-based nano-formulations and their prospect for diabetic wounds are also discussed briefly.


Subject(s)
Diabetes Mellitus , Hyperglycemia , Humans , Biocompatible Materials/pharmacology , Diabetes Mellitus/drug therapy , Wound Healing , Drug Delivery Systems
3.
Saudi J Biol Sci ; 30(9): 103778, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37663396

ABSTRACT

Pioglitazone (PGL) is an effective insulin sensitizer, however, side effects such as accumulation of subcutaneous fat, edema, and weight gain as well as poor oral bioavailability limit its therapeutic potential for oral delivery. Recent studies have shown that combination of both, PGL and fish oil significantly reduce fasting plasma glucose, improve insulin resistance, and mitigate pioglitazone-induced subcutaneous fat accumulation and weight gain. Nevertheless, developing an effective oral drug delivery system for administration of both medications have not been explored yet. Thus, this study aimed to develop a self-micro emulsifying drug delivery system (SMEDDS) for the simultaneous oral administration of PGL and fish oil. SMEDDS was developed using concentrated fish oil,Tween® 80, and Transcutol HP and optimized by central composite design (CCD). The reconstituted, optimized PGL-SMEDDS exhibited a globule size of 142 nm, a PDI of 0.232, and a zeta potential of -20.9 mV. The in-vitro drug release study of the PGL-SMEDDS showed a first-order model kinetic release and demonstrated remarkable 15-fold enhancement compared to PGL suspension. Additionally, following oral administration in fasting albino Wistar rats, PGL-SMEDDS exhibited 3.4-fold and 1.4-fold enhancements in the AUC0-24h compared to PGL suspension and PGL marketed product. The accelerated stability testing showed that the optimized SMEDDS formulation was stable over a three-month storage period. Taken together, our findings demonstrate that the developed fish oil-based SMEDDS for PGL could serve as effective nanoplatforms for the oral delivery of PGL, warranting future studies to explore its synergistic therapeutic potential in rats.

4.
Braz J Biol ; 83: e270808, 2023.
Article in English | MEDLINE | ID: mdl-37075379

ABSTRACT

Catfish (Clarias gariepinus) meat isn't preferred by consumers in compared to other fish species meat, thus to enhance the use of catfish meat, ready to eat catfish fingers were prepared with some plants additives (amla and ginger powder). The mean objective of this study was to assess the impact of amla and ginger powder on catfish finger qualities in terms of physical, chemical, microbiological, and sensorial parameters under stored at a low temperature (5 ± 1 °C). The obtained results were compared with those of a control sample (basic formula) and a sample containing the synthetic antioxidant. During the storage period, the levels of pH, thiobarbituric acid, total volatile basic nitrogen, trimethylamine, total bacteria count, psychrophilic bacteria, molds and yeasts counts increased dramatically, although the values remained within acceptable ranges. The findings also revealed, that amla and ginger powder considerably (p < 0.05) reduced the changes in quality parameters, as well as there was a considerable increase in the quality parameter in all treated samples than in the control. Finally, amla and ginger powder can be a substitute for synthetic antioxidants and antimicrobials. These findings suggest that the powder of amla and ginger are suitable for use as a natural antioxidants and antimicrobials to extend the shelf-life of animal products.


Subject(s)
Catfishes , Phyllanthus emblica , Zingiber officinale , Animals , Powders , Antioxidants/pharmacology
5.
ScientificWorldJournal ; 2022: 1552602, 2022.
Article in English | MEDLINE | ID: mdl-36479553

ABSTRACT

One of the most important issues for bitter-tasting drugs such as levocetirizine dihydrochloride (LCD) is the production of palatable dosage forms. LCD also has a delayed onset of action following oral administration. In this study, solid dispersed fast-dissolving films (FDFs) of LCD using the solvent casting method for oral application were prepared and evaluated. The FDF is composed of HPMC as the film forming polymer and different types of superdisintegrants (sodium starch glycolate, croscarmellose sodium, or crospovidone). FDF containing crospovidone showed the highest percentage release of the drug (100.54% ± 1.47 within 3 min.) and was chosen for fabricating into palatable solid dispersed FDFs using different ratios of gelatine. The results of Raman and FTIR revealed that the drug's crystalline structure has been disrupted, and the drug has intermolecular hydrogen bonds with gelatine. The solid dispersed FDF (LF-7), which contained the drug in the form of a 1 : 1 solid dispersion with gelatine, showed a rapid in vitro disintegration (25 seconds) and a burst release of the drug (99.22% ± 2.22 within one min). The in vivo studies were conducted on human participants and showed a significant (p < 0.05) reduction in disintegration time (9.43 ± 2.16 sec.) and higher taste masking ability of the solid dispersed FDF (LF-7) compared to the nonsolid dispersed FDF (LF-4). The stability studies indicated that the prepared FDF remained stable over three months. Overall, FDFs of levocetirizine dihydrochloride with a palatable and rapid onset of action were developed to relieve allergic symptoms.


Subject(s)
Humans
6.
Int J Biol Macromol ; 221: 435-445, 2022 Nov 30.
Article in English | MEDLINE | ID: mdl-36067850

ABSTRACT

This study aims to develop chitosan-coated PLGA nanoparticles intended for nose-to-brain delivery of carmustine. Formulations were prepared by the double emulsion solvent evaporation method and optimized by using Box-Behnken Design. The optimized nanoparticles were obtained to satisfactory levels in terms of particle size, PDI, entrapment efficiency, and drug loading. In vitro drug release and ex-vivo permeation showed sustained release and enhanced permeability (approx. 2 fold) of carmustine compared to drug suspension. The AUC0-t of brain obtained with carmustine-loaded nanoparticles via nasal administration in Albino Wistar rats was 2.8 and 14.7 times that of intranasal carmustine suspension and intravenous carmustine, respectively. The MTT assay on U87 MG cell line showed a significant decrease (P < 0.05) in the IC50 value of the formulation (71.23 µg ml-1) as compared to drug suspension (90.02 µg ml-1).These findings suggest chitosan coated nanoparticles could be used to deliver carmustine via intranasal administration to treat Glioblastoma multiforme.


Subject(s)
Chitosan , Glioblastoma , Nanoparticles , Animals , Rats , Administration, Intranasal , Chitosan/metabolism , Carmustine/metabolism , Glioblastoma/drug therapy , Glioblastoma/metabolism , Drug Carriers/metabolism , Brain/metabolism , Particle Size , Rats, Wistar , Drug Delivery Systems/methods
7.
Rev Sci Instrum ; 93(3): 033504, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35364989

ABSTRACT

Laser wakefield acceleration (LWFA) using PW-class laser pulses generally requires cm-scale laser-plasma interaction Rayleigh length, which can be realized by focusing such pulses inside a long underdense plasma with a large f-number focusing optic. Here, we present a new PW-based LWFA instrument at the SG-II 5 PW laser facility, which employs f/23 focusing. The setup also adapted an online probing of the plasma density via Nomarski interferometry using a probe laser beam having 30 fs pulse duration. By focusing 1-PW, 30-fs laser pulses down to a focal spot of 230 µm, the peak laser intensity reached a mild-relativistic level of 2.6 × 1018 W/cm2, a level modest for standard LWFA experiments. Despite the large aspect ratio of >25:1 (transverse to longitudinal dimensions) of the laser pulse, electron beams were observed in our experiment only when the laser pulse experienced relativistic self-focusing at high gas-pressure thresholds, corresponding to plasma densities higher than 3 × 1018 cm-3.

8.
J Neurosci ; 2021 Jun 08.
Article in English | MEDLINE | ID: mdl-34103360

ABSTRACT

Neuro-immune interaction during development is strongly implicated in the pathogenesis of neurodevelopmental disorders, but the mechanisms that cause neuronal circuit dysregulation are not well understood. We performed in vivo imaging of the developing retinotectal system in the larval zebrafish to characterize the effects of immune system activation on refinement of an archetypal sensory processing circuit. Acute inflammatory insult induced hyper-dynamic remodeling of developing retinal axons in larval fish and increased axon arbor elaboration over days. Using calcium imaging in GCaMP6s transgenic fish we showed that these morphological changes were accompanied by a shift toward decreased visual acuity in tectal cells. This finding was supported by poorer performance in a visually guided behavioral task. We further found that the pro-inflammatory cytokine, interleukin-1ß (IL-1ß) is upregulated by the inflammatory insult, and that down-regulation of IL-1ß abrogated the effects of inflammation on axonal dynamics and growth. Moreover, baseline branching of the RGC arbors in IL-1ß morphant animals was significantly different from that in control larvae, and their performance in a predation assay was impaired, indicating a role for this cytokine in normal neuronal development. This work establishes a simple and powerful non-mammalian model of developmental immune activation and demonstrates a role for IL-1ß in mediating the pathological effects of inflammation on neuronal circuit development.SIGNIFICANCE STATEMENTMaternal immune activation (MIA) can increase the risk of neurodevelopmental disorders in offspring, however the mechanisms involved are not fully understood. Using a non-mammalian vertebrate model of developmental immune activation, we show that even brief activation of inflammatory pathways has immediate and long-term effects on the arborization of axons, and that these morphological changes have functional and behavioral consequences. Finally, we show that the pro-inflammatory cytokine IL-1ß plays an essential role in both the effects of inflammation on circuit formation and normal axonal development. Our data add to a growing body of evidence supporting epidemiological studies linking immune activation to neurodevelopmental disorders, and help shed light on the molecular and cellular processes that contribute to the etiology of these disorders.

9.
J Infect Public Health ; 14(6): 787-794, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34022738

ABSTRACT

The Middle East, Eastern Europe, Central Asia and North Africa Rabies Control Network (MERACON), is built upon the achievements of the Middle East and Eastern Europe Rabies Expert Bureau (MEEREB). MERACON aims to foster collaboration among Member States (MS) and develop shared regional objectives, building momentum towards dog-mediated rabies control and elimination. Here we assess the epidemiology of rabies and preparedness in twelve participating MS, using case and rabies capacity data for 2017, and compare our findings with previous published reports and a predictive burden model. Across MS, the number of reported cases of dog rabies per 100,000 dog population and the number of reported human deaths per 100,000 population as a result of dog-mediated rabies appeared weakly associated. Compared to 2014 there has been a decrease in the number of reported human cases in five of the twelve MS, three MS reported an increase, two MS continued to report zero cases, and the remaining two MS were not listed in the 2014 study and therefore no comparison could be drawn. Vaccination coverage in dogs has increased since 2014 in half (4/8) of the MS where data are available. Most importantly, it is evident that there is a need for improved data collection, sharing and reporting at both the national and international levels. With the formation of the MERACON network, MS will be able to align with international best practices, while also fostering international support with other MS and international organisations.


Subject(s)
Dog Diseases , Rabies , Africa, Northern/epidemiology , Animals , Dog Diseases/epidemiology , Dog Diseases/prevention & control , Dogs , Europe, Eastern , Middle East/epidemiology , Rabies/epidemiology , Rabies/prevention & control , Rabies/veterinary
10.
Article in English | MEDLINE | ID: mdl-33880073

ABSTRACT

Dementia is a term that encompasses a group of clinical symptoms affecting memory, thinking and social abilities, characterized by progressive impairment of memory performance and cognitive functions. There are several factors involved in the pathogenesis and progression of dementia, such as old age, brain ischemia, toxin exposure, and oxidative stress. There are extensive similarities between dementia and Alzheimer's disease (AD) either in clinical manifestations or experimental animal models. AD is the most dominant form of dementia, characterized by the accumulation of beta-amyloid protein and cholinergic neurotransmission deficits in the brain. Currently available medications for the treatment of dementia, such as choline esterase inhibitors, N-methyl-D-aspartate (NMDA) antagonists (memantine), have short-term efficacy and only relieve symptoms rather than targeting the main underlying pathogenesis. Several animal studies and clinical trials are being conducted to provide a rational approach to these medicinal plants in the prevention or treatment of memory deficits. This review highlights the potential effects of medicinal plants and their derived lead molecules, and explains the related mechanisms and effects reviewed from published literature as major thrust aspects and hopeful strategies in the prevention or treatment of dementia.

11.
Eur Urol Focus ; 7(5): 1035-1043, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33386289

ABSTRACT

BACKGROUND: En-bloc resection of bladder tumors achieves complete tumor removal, improves the quality of resection, decreases perioperative complication, and potentially improves recurrence rates. OBJECTIVE: To assess the efficacy and safety of holmium laser en-bloc resection (HolERBT) versus conventional transurethral resection of bladder tumor (cTURBT). DESIGN, SETTING, AND PARTICIPANTS: Between September 2015 and September 2018, 100 patients with non-muscle-invasive bladder cancer were randomly allocated to cTURBT or HolERBT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was detection of residual tumor in reTURBT specimens at 4 wk after the primary resection. Operative parameters, specimen quality, perioperative complications, and recurrence-free survival (RFS) were compared. Independent sample t tests, χ2 tests, and Kaplan-Meier curves were used, as appropriate. RESULTS AND LIMITATIONS: The patient and tumor baseline characteristics were comparable between the groups. Residual tumors were detected in 7% and 27.7% of cases after HolERBT and cTURBT, respectively (p=0.01). Detrusor muscle was sampled in 98% of HolERBT and 62% of cTURBT cases (p<0.001). Lamina propria invasion substaging was feasible in only 68.2% of HolERBT and 18.4% of cTURBT cases (p<0.001). Following HolERBT, catheterization time (p<0.001) and hospital stay (p=0.001) were shorter when compared to cTURBT. Immediate postoperative instillation of chemotherapy in indicated cases was feasible for 100% of the HolERBT group and 91.5% of the cTURBT group (p=0.04). After follow-up of 20 ± 9.9 mo (13-36), RFS was 31.76 mo (95% confidence interval [CI] 28.67-34.86) in the HolERBT group and 28.25 mo (95% CI 24.87-31.64) in the cTURBT group (hazard ratio 0.43, 95% CI 0.17-1.1; p=0.07). However, this study was not powered to detect a difference in RFS. CONCLUSIONS: Compared to cTURBT, HolERBT is a safer procedure for bladder tumor resection. It fulfills the oncological criteria of optimized resection with less residual tumor and better specimen quality. PATIENT SUMMARY: En-bloc resection of bladder cancer tumors using a holmium laser is safer than the conventional technique. It has the advantages of less residual tumor and better specimen quality, with a similar tumor recurrence rate. This study is registered at ClinicalTrials.gov as NCT02555163.


Subject(s)
Lasers, Solid-State , Urinary Bladder Neoplasms , Cystectomy/methods , Humans , Lasers, Solid-State/therapeutic use , Neoplasm, Residual/surgery , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgery , Urologic Surgical Procedures/methods
12.
BJU Int ; 126(6): 731-738, 2020 12.
Article in English | MEDLINE | ID: mdl-32633020

ABSTRACT

OBJECTIVE: To compare transurethral resection in saline (TURIS), Greenlight laser vapo-enucleation of the prostate (GL.PVEP), and holmium laser enucleation of the prostate (HoLEP), for controlling lower urinary tract symptoms secondary to large benign prostatic hyperplasia (BPH) and to assess non-inferiority of 3-year re-treatment rates. PATIENTS AND METHODS: Eligible patients with BPH (prostate size 80-150 mL) were randomly assigned to one of the intervention groups. Non-inferiority of re-treatment rate was evaluated using a one-sided test at 5% level of significance. RESULTS: At the time of analysis, 60 GL.PVEP, 60 HoLEP and 62 TURIS procedures were included. Perioperative parameters were comparable between groups; however, the operative time was longer in GL.PVEP vs HoLEP and TURIS, at a mean (SD) of 92 (32) vs 73 (30) and 83 (28) min (P = 0.005); and was less effective with a mean (SD) removal of 1.2 (0.4) vs 1.7 (0.7) and 1.4 (0.6) g/min (P < 0.001), respectively. Perioperative complications and need for auxiliary procedures were similar in the three groups; however, there was a significantly higher rate of capsular perforation in TURIS group (five, 8%) compared to one (1.6%) in the GL.PVEP group and none in the HoLEP group (P = 0.01). There was a significantly longer hospital stay, catheter-time and higher rate of blood transfusion in the TURIS group. There was significant but comparable improvements in the International Prostate Symptom Score in three groups at different follow-up points. At 3 years, re-treatment for recurrent bladder outlet obstruction was required more after GL.PVEP and TURIS. More re-do surgeries for recurrent obstructing prostate adenoma was reported after GL.PVEP (four, 6.7%) and TURIS (six, 9.7%) than for HoLEP (none) (P = 0.04). CONCLUSION: The perioperative outcomes of GL.PVEP and HoLEP surpassed that of TURIS for the treatment of large prostates, but with a significantly prolonged operative time with GL.PVEP. The three techniques achieve good functional outcomes; however, 3-year re-treatment rates following TURIS and GL.PVEP were inferior to HoLEP.


Subject(s)
Laser Therapy , Prostate/surgery , Prostatic Hyperplasia/surgery , Transurethral Resection of Prostate , Aged , Humans , Laser Therapy/adverse effects , Laser Therapy/methods , Laser Therapy/statistics & numerical data , Male , Middle Aged , Postoperative Complications , Transurethral Resection of Prostate/adverse effects , Transurethral Resection of Prostate/methods , Transurethral Resection of Prostate/statistics & numerical data , Treatment Outcome
13.
Sci Adv ; 5(11): eaav7940, 2019 11.
Article in English | MEDLINE | ID: mdl-31803828

ABSTRACT

A typical laser-plasma accelerator (LPA) is driven by a single, ultrarelativistic laser pulse from terawatt- or petawatt-class lasers. Recently, there has been some theoretical work on the use of copropagating two-color laser pulses (CTLP) for LPA research. Here, we demonstrate the first LPA driven by CTLP where we observed substantial electron energy enhancements. Those results have been further confirmed in a practical application, where the electrons are used in a bremsstrahlung-based positron generation configuration, which led to a considerable boost in the positron energy as well. Numerical simulations suggest that the trailing second harmonic relativistic laser pulse is capable of sustaining the acceleration structure for much longer distances after the preceding fundamental pulse is depleted in the plasma. Therefore, our work confirms the merits of driving LPAs by two-color pulses and paves the way toward a downsizing of LPAs, making their potential applications in science and technology extremely attractive and affordable.

14.
Arab J Urol ; 17(3): 216-220, 2019.
Article in English | MEDLINE | ID: mdl-31489238

ABSTRACT

Objective: To evaluate the efficacy and safety of botulinum toxin A (BoNT-A) instillation in the bladder under the effect of low-energy shockwaves (LESWs) for the treatment of refractory idiopathic overactive bladder (OAB). Patients and methods: A preliminary clinical study was conducted, including 15 patients with refractory OAB, between September 2016 and July 2017. Intravesical instillation of 100 IU of BoNT-A was done followed by LESWs (3000 shocks over 10 min) exposure to the supra-pubic area. Patients were followed-up by urine analysis, urine culture, post-void residual urine volume (PVR), and Overactive Bladder Symptom Score (OABSS) at 1, 2 and 3 months. Results: There were statistically significant improvements in all OABSS domains and the total score after 1 and 2 months of treatment (P < 0.05). Whereas, only the nocturia domain remained significantly improved after 3 months (P = 0.02). There was no significant increase in PVR throughout the study period (P > 0.05) and none of the patients required clean intermittent catheterisation. Two, two and three patients developed urinary tract infections after 1, 2 and 3 months, respectively. Conclusion: Intravesical instillation of BoNT-A and LESWs is safe and effective method for the treatment of refractory OAB with a durable response for 2 months. Abbreviations: BoNT-A: botulinum toxin A; CIC: clean intermittent catheterisation; DO: detrusor overactivity; LESWs: low-energy shockwaves; OAB: overactive bladder; OABSS: Overactive Bladder Symptom Score; Qmax: maximum urinary flow rate; QoL: quality of life; UUI: urgency urinary incontinence.

15.
J Neuroendocrinol ; 31(2): e12682, 2019 02.
Article in English | MEDLINE | ID: mdl-30597689

ABSTRACT

Although dehydroepiandrosterone (DHEA) may exert neuroprotective effects in the developing brain, prolonged or excessive elevations in cortisol may exert neurotoxic effects. The ratio between DHEA and cortisol (DC ratio) has been linked to internalising and externalising disorders, as well as cognitive performance, supporting the clinical relevance of this hormonal ratio during development. However, the brain mechanisms by which these effects may be mediated have not yet been identified. Furthermore, although there is evidence that the effects of cortisol in the central nervous system may be sexually dimorphic in humans, the opposite is true for DHEA, with human studies showing no sex-specific associations in cortical thickness, cortico-amygdalar or cortico-hippocampal structural covariance. Therefore, it remains unclear whether sex moderates the developmental associations between DC ratio, brain structure, cognition and behaviour. In the present study, we examined the associations between DC ratio, structural covariance of the hippocampus with whole-brain cortical thickness, and measures of personality, behaviour and cognition in a longitudinal sample of typically developing children, adolescents and young adults aged 6-22 years (N = 225 participants [F = 128]; 355 scans [F = 208]), using mixed effects models that accounted for both within- and between-subject variances. We found sex-specific interactions between DC ratio and anterior cingulate cortex-hippocampal structural covariance, with higher DC ratios being associated with a more negative covariance between these structures in girls, and a more positive covariance in boys. Furthermore, the negative prefrontal-hippocampal structural covariance found in girls was associated with higher verbal memory and mathematical ability, whereas the positive covariance found in boys was associated with lower cooperativeness and reward dependence personality traits. These findings support the notion that the ratio between DHEA and cortisol levels may contribute, at least in part, to the development of sex differences in cognitive abilities, as well as risk for internalising/externalising disorders, via an alteration in prefrontal-hippocampal structure during the transition from childhood to adulthood.


Subject(s)
Dehydroepiandrosterone/metabolism , Hippocampus/anatomy & histology , Hydrocortisone/metabolism , Mental Processes/physiology , Personality/physiology , Prefrontal Cortex/anatomy & histology , Sex Characteristics , Adolescent , Adult , Child , Dehydroepiandrosterone/analysis , Executive Function/physiology , Female , Hippocampus/growth & development , Humans , Hydrocortisone/analysis , Learning/physiology , Male , Memory/physiology , Neuropsychological Tests , Prefrontal Cortex/growth & development , Young Adult
16.
J Genet ; 97(4): 925-930, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30262704

ABSTRACT

Developmental dysplasia of the hip (DDH) is a congenital condition characterized by abnormality in acetabulum size and/or shape. The incidence rate of DDH differs between different populations with risk factors including positive family history, breech presentation, sex, firstborn status, side of the hip, mode of delivery and oligohydramnios. It is recognized that DDH has a genetic component that exhibit autosomal dominant patterns. Many candidate genes have been studied and found to be associated with the disease; most of them are normally involved in cartilage development and joint metabolism. In this study, the association of four single-nucleotide polymorphisms (SNPs) (rs731236, rs1544410, rs7975232 and rs2228570) in the vitamin D receptor (VDR) gene was studied by a case-control analysis. The study sample involves 50 cases with confirmed DDH presentation and 50 nonDDH controls. SNPs were genotyped using conventional polymerase chain reaction (PCR) and restriction fragment-length polymorphism (RFLP) techniques. Genotype and allele frequencies were analysed using SPSS software. No significant associations were found between the VDR polymorphisms analysed and DDH. Further work need to be performed using genomewide analysis to elucidate the genetic basis of DDH.


Subject(s)
Developmental Disabilities/genetics , Genetic Predisposition to Disease , Hip Dislocation/genetics , Receptors, Calcitriol/genetics , Alleles , Developmental Disabilities/physiopathology , Female , Gene Frequency , Genetic Association Studies , Genotype , Hip Dislocation/physiopathology , Humans , Male , Polymorphism, Single Nucleotide , Risk Factors
17.
Psychoneuroendocrinology ; 98: 86-94, 2018 12.
Article in English | MEDLINE | ID: mdl-30121549

ABSTRACT

There is accumulating evidence that both dehydroepiandrosterone (DHEA) and cortisol play an important role in regulating physical maturation and brain development. High DHEA levels tend to be associated with neuroprotective and indirect anabolic effects, while high cortisol levels tend to be associated with catabolic and neurotoxic properties. Previous literature has linked the ratio between DHEA and cortisol levels (DC ratio) to disorders of attention, emotional regulation and conduct, but little is known as to the relationship between this ratio and brain development. Due to the extensive links between the amygdala and the cortex as well as the known amygdalar involvement in emotional regulation, we examined associations between DC ratio, structural covariance of the amygdala with whole-brain cortical thickness, and validated report-based measures of attention, working memory, internalizing and externalizing symptoms, in a longitudinal sample of typically developing children and adolescents 6-22 years of age. We found that DC ratio predicted covariance between amygdalar volume and the medial anterior cingulate cortex, particularly in the right hemisphere. DC ratio had a significant indirect effect on working memory through its impact on prefrontal-amygdalar covariance, with higher DC ratios associated with a prefrontal-amygdalar covariance pattern predictive of higher scores on a measure of working memory. Taken together, these findings support the notion, as suggested by animal and in vitro studies, that there are opposing effects of DHEA and cortisol on brain development in humans, and that these effects may especially target prefrontal-amygdalar development and working memory, in a lateralized fashion.


Subject(s)
Amygdala/growth & development , Memory, Short-Term/physiology , Prefrontal Cortex/growth & development , Adolescent , Amygdala/drug effects , Amygdala/metabolism , Attention/physiology , Brain/growth & development , Cerebral Cortex/growth & development , Child , Child Development , Dehydroepiandrosterone/metabolism , Emotions/physiology , Female , Humans , Hydrocortisone/metabolism , Image Processing, Computer-Assisted , Longitudinal Studies , Male , Neurogenesis/physiology , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Puberty/physiology , Young Adult
18.
Pediatr Surg Int ; 34(9): 967-970, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30051148

ABSTRACT

BACKGROUND: After definitive repair of esophageal atresia (EA) and tracheoesophageal fistula (TEF), a chest tube (CT) may be left in place to diagnose and conservatively treat a postoperative anastomotic leak, although its necessity is controversial. The purpose of this study was to determine if the use of a CT decreases rates of early postoperative complications after EA and TEF repair. METHODS: A retrospective chart review was performed to identify all patients with EA and TEF who underwent repair between 1985 and 2012. Univariate analysis was performed to compare patients who did or did not have a CT in terms of preoperative characteristics and postoperative outcomes. RESULTS: One hundred twenty neonates were included; 69 had a CT inserted intraoperatively, while 51 did not. The two groups were similar in terms of patient characteristics. There was no statistically significant difference between the groups in terms of length of hospital stay (31 ± 12 vs. 36 ± 16 days, p = 0.5), or complication rates (13% vs. 12%, p = 0.9) for those with or without CT, respectively. CONCLUSIONS: The use of a CT does not alter early postoperative complications after EA/TEF repair.


Subject(s)
Chest Tubes , Esophageal Atresia/surgery , Tracheoesophageal Fistula/surgery , Anastomotic Leak/diagnosis , Anastomotic Leak/therapy , Female , Humans , Infant, Newborn , Length of Stay , Male , Ontario , Postoperative Complications , Reoperation/statistics & numerical data , Retrospective Studies
19.
Folia Morphol (Warsz) ; 77(4): 609-619, 2018.
Article in English | MEDLINE | ID: mdl-29802712

ABSTRACT

BACKGROUND: Morphology and histology of filum terminale (FT) has a role in the pathophysiology of tethered cord syndrome (TCS). This research was implemented to investigate the morphometric parameters and histological structure of normal FT in adult human cadavers and magnetic resonance imaging (MRI) scans to correlate them with the pathophysiology of TCS. MATERIALS AND METHODS: Twenty five adult human cadavers (15 males, 10 females) and 100 MRI echo scans of lumbosacral region (50 males and 50 females), were used in this study. MRI patients were divided into 21-40 and 41-60 age groups. The cadavers were dissected at the prone position to explore their fila. The length of FT, filum terminale internum (FTI), filum terminale externum (FTE), vertebral level of beginning, dural piercing and termination of FT, and the initial, midpoint, and mid-FTE diameters were determined. Four segments were excised from lower conus, upper, middle, and lower thirds of FT. The specimens were processed for light microscopic examination. Statistical analysis was done for these parameters. RESULTS: MRI morphometrical parameters of FT, except FTI length, revealed no age effect or sex differences, where length of FTI, FTE, initial diameter, level of conus medullaris termination (CMT) and dural sac termination (DST) were 174.1 ± 16.8, 75.8 ± 9.5, 1.6 ± 0.21, L1-2 and S2U in males and 166.9 ± 18.9, 74.1 ± 9.3, 1.53 ± 0.25, L1-2 and S2M vertebrae in females, respectively. However, non-significant sex difference was observed in morphometric parameters of cadaveric FT, where length of FTI and FTE, initial diameter, CMT and DST levels were 164.2 ± 11.6, 76.7 ± 8.1, 1.7 ± 0.14, L1L and S2U vertebrae in males and 159.2 ± 10.1, 71.02 ± 7.3, 1.6 ± 0.29, L1L and S2U in females, respectively. Moreover, CMT below L2 vertebra was seen in 5% of MRI scans and 8% of cadavers. Also, the initial diameter of FT > 2 mm was recorded in 7% of MRI and 8% of cadaveric cases. Histologically, the structure of FT showed gradual reduction in nervous, glial, and vascular tissues with converse increase in collagen content in FTE compared with those of FTI. CONCLUSIONS: Knowledge of the morphometric parameters and the histological structure of FT are necessary for clinicians who dealing with diagnosis or treatment of tethered cord syndrome.


Subject(s)
Cauda Equina/diagnostic imaging , Lumbar Vertebrae/diagnostic imaging , Magnetic Resonance Imaging , Spinal Cord/diagnostic imaging , Adult , Cadaver , Female , Humans , Lumbosacral Region/diagnostic imaging , Male
20.
Aliment Pharmacol Ther ; 47(3): 421-431, 2018 02.
Article in English | MEDLINE | ID: mdl-29193226

ABSTRACT

BACKGROUND: Treatment of chronic hepatitis C using combination of sofosbuvir (SOF) and daclatasvir (DCV) was used in several clinical trials and multicentre studies, which were somewhat limited to genotypes 1-3. The national program in Egypt is using SOF-DCV combination for large scale treatment. AIM: To assess the efficacy and safety of combined SOF-DCV in treating patients with HCV-G4 in a real-world setting. METHODS: Data and outcome of chronic HCV patients who were treated for 12 weeks with generic medications: DCV 60 mg plus SOF 400 mg ± ribavirin (RBV) within the national hepatitis C treatment program in Egypt are presented. Treatment-naïve patients without cirrhosis were treated without RBV, and those who had cirrhosis or were treatment-experienced (interferon experienced or SOF experienced) received RBV. Efficacy and safety were assessed, and baseline factors associated with sustained virological response at post-treatment week 12 (SVR12) were explored. RESULTS: During the first 2 months of the programme, 18 378 patients with HCV-G4 started treatment with SOF-DCV with or without RBV. Overall, 95.1% achieved SVR12 (95.4% among patients treated without RBV and 94.7% for patients treated with RBV, P = .32). Treatment was prematurely discontinued in only 1.5% of patients. The most common events leading to discontinuation were patient withdrawal (n = 76) and pregnancy (n = 5). Five deaths occurred within this group. CONCLUSIONS: Real-world experience of generic SOF-DCV in patients with chronic HCV-G4 proved to be safe and associated with a high SVR12 rate, in patients with different stages of fibrosis.


Subject(s)
Antiviral Agents/administration & dosage , Drugs, Generic/administration & dosage , Hepatitis C, Chronic/drug therapy , Imidazoles/administration & dosage , Ribavirin/administration & dosage , Sofosbuvir/administration & dosage , Adult , Antiviral Agents/adverse effects , Carbamates , Drug Therapy, Combination/adverse effects , Drugs, Generic/adverse effects , Egypt/epidemiology , Female , Hepatitis C, Chronic/epidemiology , Humans , Imidazoles/adverse effects , Liver Cirrhosis/drug therapy , Liver Cirrhosis/epidemiology , Liver Cirrhosis/virology , Male , Middle Aged , Pyrrolidines , Retrospective Studies , Ribavirin/adverse effects , Sofosbuvir/adverse effects , Sustained Virologic Response , Treatment Outcome , Valine/analogs & derivatives
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