Abstract
Following implantation, the human embryo undergoes major morphogenetic transformations that establish the future body plan. While the molecular events underpinning this process are ...established in mice, they remain unknown in humans. Here we characterise key events of human embryo morphogenesis, in the period between implantation and gastrulation, using single-cell analyses and functional studies. First, the embryonic epiblast cells transition through different pluripotent states and act as a source of FGF signals that ensure proliferation of both embryonic and extra-embryonic tissues. In a subset of embryos, we identify a group of asymmetrically positioned extra-embryonic hypoblast cells expressing inhibitors of BMP, NODAL and WNT signalling pathways. We suggest that this group of cells can act as the anterior singalling centre to pattern the epiblast. These results provide insights into pluripotency state transitions, the role of FGF signalling and the specification of anterior-posterior axis during human embryo development.
The objective of the study was to evaluate the drug-drug interaction studies of levoceterizine with atenolol. Calibration curve studies of working standard solutions of levocetirizine and atenolol ...（0.01-0.1 mmol） were scanned. Maxima appeared at 231 nm for levocetirizine and 224 nm for atenolol. The calibration curve obeyed Beer Lambert＇s Law. Lone availabilities of both the drugs were studied in pH 1, pH 4, pH 7.4 and pH 9 at 37℃ on B.P. （British Pharmacopoeia） dissolution apparatus. To study the drug-drug interaction of levocetirizine （5 mg tablet） and atenolol （100 mg tablet）, both the drugs were introduced to the dissolution apparatus in simulated gastric juice （pH 1）, pH 4, pH 7.4 and pH 9 at 37℃ at zero time and measured the absorbance maxima of both the drugs at the corresponding wavelength. Graphs were plotted for availability percentage （%） of drug versus time at each set of experiment. The availability percentage （%） of levocetirizine in the buffers of pH simulated to gastric pH 4, pH 7.4 and pH 9 in the presence of atenolol was 436.78%, 376.90%, 436.78% and 436.78%, respectively, but the availability of atenolol was increased up to 214.80%, 212.96%, 214.93% and 231.51% in simulated to gastric pH and in the buffers ofpH 4, pH 7.4 and pH 9, respectively. On the basis of these studies, it is concluded that levocetirizine forms a charge-complex with atenolol; therefore, co-administration of these drugs should be avoided.
This study investigated the role of genetic variant rs8177374 in MAL/TIRAP gene in mediating the cytokine levels of IFN-γ, TNF-α, IL-10, and TGF-β in malaria patients due to Plasmodium falciparum or ...P. vivax infection. The study included human blood samples collected from patients with malaria (n = 228) and healthy controls (n = 226). P. falciparum and P. vivax groups were established based on the causative species of Plasmodium. Malaria samples were divided into mild and severe malaria groups based on the symptoms that appeared in the patients, according to the WHO criteria. In a previous study, we genotyped rs8177374 via allele specific PCR strategy. In this study, cytokine levels were estimated in the blood plasma of rs8177374 genotype samples via Sandwich Enzyme Linked Immunosorbent Assay kits. Increased IFN-γ and TNF-α levels in presence of CC genotype indicates the role of CC genotype in both severe and mild malaria groups. Enhanced IL-10 levels in the CT genotype and mild malaria groups suggest a role of CT genotype and IL-10 in the mild clinical outcomes of malaria. The rs8177374 polymorphism in MAL/TIRAP plays an important role in malaria pathogenesis.
Preemptive analgesia is used for postoperative pain management, providing pain relief with few adverse effects. In this study, the effect of a preemptive regime on rat behavior and
expression in the ...spinal cord of the uterine surgical pain model was evaluated. It was a lab-based experimental study in which 60 female Sprague-Dawley rats; eight to 10 weeks old, weighing 150-300 gm were used. The rats were divided into two main groups: (i) superficial pain group (SG) (with skin incision only), (ii) deep pain group (with skin and uterine incisions). Each group was further divided into three subgroups based on the type of preemptive analgesia administered i.e., "tramadol, buprenorphine, and saline subgroups." Pain behavior was evaluated using the "Rat Grimace Scale" (RGS) at 2, 4, 6, 9 and 24 h post-surgery. Additionally,
immunohistochemistry was performed on sections from spinal dorsal horn (T12-L2), and its expression was evaluated using optical density and mean cell count 2 hours postoperatively. Significant reduction in the RGS was noted in both the superficial and deep pain groups within the tramadol and buprenorphine subgroups when compared to the saline subgroup (
≤ .05). There was a significant decrease in
expression both in terms of number of
positive cells and the optical density across the superficial laminae and lamina X of the spinal dorsal horn in both SD and DG (
≤ .05). In contrast, the saline group exhibited c-fos expression primarily in laminae I-II and III-IV for both superficial and deep pain groups and lamina X in the deep pain group only (
≤ .05). Hence, a preemptive regimen results in significant suppression of both superficial and deep components of pain transmission. These findings provide compelling evidence of the analgesic efficacy of preemptive treatment in alleviating pain response associated with uterine surgery.
Aerobic vaginitis is a recently described vaginal infection that is treated with antibiotics, which cause undesirable effects leading to disturbance in normal vaginal flora and antibiotic resistance ...among pathogens. Probiotics may be considered as a natural alternative therapy. We investigated antagonistic and immunomodulatory potential of intravaginally administered probiotic Lactobacillus reuteri-MT180537 against vaginal colonization by Enterococcus faecalis-MW051601 in mice. In vitro antimicrobial potential of lactic acid bacteria was determined against major pathogens of aerobic vaginitis. Moreover, in vivo prophylactic efficacy of L. reuteri-MT180537 against E. faecalis-MW051601 induced AV, in β-estradiol immunosuppressed mice was determined for the first time. Lactic acid bacteria displayed antibacterial activity against pathogens with zone of inhibition (11.33–20.00 mm) and co-aggregation (40–67%). Animals receiving L. reuteri-MT180537 followed by E. faecalis-MW051601 challenge exhibited significant reduction in clinical index, vaginal bacterial load, and histopathological changes in vaginal tissues compared to animals receiving E. faecalis-MW051601 only. L. reuteri-MT180537 upregulated expression of anti-inflammatory (Foxp3, IFN-γ) cytokines and resulted in controlling E. faecalis-MW051601 induced over expression of pro-inflammatory (IL-6, IL-1β) cytokines. Altogether, L. reuteri-MT180537 displayed antagonistic properties in vitro and prevented aerobic vaginitis by inhibiting the growth of E. faecalis-MW051601 and regulating expression of pro-inflammatory and anti-inflammatory cytokines in mice.
Congenital heart defects (CHDs) are the heart structural malformations present at birth. Septal defects account for 40% of CHD, including atrial, ventricular and atrioventricular septal defects. In ...Pakistan, the prevalence of CHD is 3.4 in 1000, and a study estimated that 60,000 babies are born with CHD annually. Methylenetetrahydrofolate reductase (MTHFR), a chief enzyme, involved in the folate metabolism. The missense mutation, C677T (rs1801133), exists in MTHFR gene, results in a MTHFR thermolabile variant having low enzymatic activity. The study is aim to identify the MTHFR C677T variant association with septal defects.
Samples of 194 CHD patients (age Formula: see text= 5.8 ± 5.1) and 50 normal echo controls (age Formula: see text= 6.0 ± 4.9), confirmed by pediatric consultant, were collected. Extracted DNA, quantified by agarose gel electrophoresis and nanodrop, was screened for SNP by high-resolution melting (HRM). Further, HRM results were confirmed using restriction analysis and sequencing. HRM was simply and precisely genotyped the samples within 3 h at low cost.
Genotypic data suggested that heterozygous mutant (CT) was frequent in congenital septal defect patients (0.26) which was higher than controls (0.143), p > 0.05. Mutant (TT) genotype was not found in this study.
rs1801133 has lack of significant association with congenital septal defects. The absence of TT genotype in this study suggesting the role of natural selection in targeted population. HRM is an easy, fast and next generation of PCR, which may be used for applied genomics.
Effects of the uniform transverse magnetic field on the transient free convective flows of a nanofluid with generalized thermal transport between two vertical parallel plates have been analyzed. The ...fluid temperature is described by a time-fractional differential equation with Caputo derivatives. Closed form of the temperature field is obtained by using the Laplace transform and fractional derivatives of the Wright’s functions. A semi-analytical solution for the velocity field is obtained by using the Laplace transform coupled with the numerical algorithms for the inverse Laplace transform elaborated by Stehfest and Tzou. Effects of the derivative fractional order and physical parameters on the nanofluid flow and heat transfer are graphically investigated.
تهدف الدراسة إلى تقييم ما إذا كان العلاج التعريفي للهيموجلوبين الجنيني قادرا على تقييد أو حتى عكس التغيرات العظمية الرأسية المرتبطة لدى مرضى الثلاسيميا بيتا.
لقد كانت دراسة رصدية مقارنة. تم تقسيم ما ...مجموعه 90 مشاركا بالتساوي إلى 3 مجموعات، مجموعة السيطرة ومجموعتي مرضى الثلاسيميا الكبرى الذين يخضعون لعمليات نقل الدم (مجموعة ثلاسيميا بيتا وأولئك الذين يتلقون العلاج التعريفي مع نقل الدم). بالإضافة إلى التاريخ والفحص، خضع جميع هؤلاء المرضى للتقييم الفوتوغرافي والتقييم الشعاعي باستخدام مخطط الرأس الجانبي. تم استخدام أنوفا أحادي الاتجاه متبوعا باختبار توكي اللاحق لتحديد الاختلافات بين المجموعات الثلاث.
اختلف العلاج التعريفي مع مجموعة نقل الدم بشكل كبير من حيث جميع الصور الفوتوغرافية وجدول الجمجمة وأغلبية المعلمات الرأسية مثل زوايا الوجه وارتفاعات الوجه الوسطى والسفلى والزاوية بين القواطع (ع = 0.036) من مجموعة الثلاسيميا بيتا حيث كانت القيم المتوسطة للعلاج التعريفي إلى جانب مجموعة نقل الدم مماثلة تقريبا لتلك الخاصة بالمجموعة الضابطة. بالإضافة إلى ذلك، كانت بعض قياسات الأسنان والأنسجة الرخوة أيضا فرقا كبيرا بين المجموعات الثلاث. بالنسبة لغالبية هذه المعلمات، أظهر متوسط الفرق قيما أعلى لمجموعة بيتا ثلاسيميا.
يبدو أن العلاج التعريفي قد أدى إلى تحسين زوايا الوجه والارتفاعات والزاوية بين القواطع بينما لوحظ نمط الهيكل العظمي من الدرجة الثانية في مجموعة نقل الدم فقط. تشير هذه النتائج إلى أن العلاج بتعريف الهيموجلوبين الجنيني ربما يكون قد قيد بعض التغيرات في قياسات الرأس لدى مرضى الثلاسيميا بيتا.
We aimed to determine the effects of fetal hemoglobin induction therapy in restricting or even reversing the cephalometric changes associated with beta thalassemia.
In this comparative observational study, 90 participants were equally divided into three groups: a control group; patients with thalassemia major receiving blood transfusion (BT group); and patients receiving induction therapy (i.e., hydroxyl urea (5–10 mg/kg/day) or as much as 20 mg/kg/day) and thalidomide (2–10 mg/kg/day) along with blood transfusion (IT group). All patients underwent history taking and examination, photographic assessment, and radiographic evaluation with a lateral cephalogram. One-way ANOVA followed by post-hoc Tukey test was used to determine differences among groups.
The IT group differed significantly from the BT group in all photographic and skull table parameters, and most cephalometric parameters, such as facial angle (p ≤ 0.001), middle and lower facial heights (p ≤ 0.001), and inter-incisal angle (p = 0.036); the mean values in the IT group were similar to those in the control group. In-addition, dental and soft tissue measurements significantly differed among groups. For most parameters, the mean difference indicated higher values in the BT group.
Induction therapy appeared to improve the facial angles, heights, and inter-incisal angles, whereas a class II skeletal pattern was observed in the transfusion only group. These findings suggest that fetal hemoglobin induction therapy might have restricted some of the cephalometric changes in patients with beta thalassemia.
This study investigated the role of genetic variant rs8177374 in MAL/TIRAP gene in mediating the cytokine levels of IFN-γ, TNF-α, IL-10 and TGF-β in malaria patients due to P. falciparum or P. vivax ...infection. The study included human blood samples of malaria patients (n=228) and healthy controls (n=226). P. falciparum and P. vivax groups were established based on the causative species of Plasmodium. Malaria samples were divided into mild and severe malaria groups based on symptoms appeared in patients as per WHO criteria. In previous study, we genotyped rs8177374 via allele specific PCR based strategy. In this study, cytokines levels were estimated from blood plasma of samples of genotypes of rs8177374 via Sandwich Enzyme Linked Immunosorbent Assay kits. Increased levels of IFN-γ and TNF-α in presence of CC genotype indicates the role of CC genotype in both severe malaria and mild malaria groups. Enhanced levels of IL-10 in CT genotype and mild malaria group suggest the role of CT genotype and IL-10 in mild clinical outcomes of malaria. rs8177374 polymorphism of MAL/TIRAP gene has important role in malaria pathogenesis.
Leptospirosis is a zoonotic disease and a worldwide public health problem that affects mainly high-risk groups. Characterizing knowledge, attitude, and practice (KAP) among high-risk groups is ...important to develop appropriate prevention programs. Here, we performed a cross-sectional study among 300 visitors of a recreational forest in Malaysia to examine leptospirosis KAP and demographics. These variables were integrated to create knowledge and practice scores for each respondent. All respondents had heard about leptospirosis, and 87% of them correctly identified it as a disease. The majority of respondents had high knowledge (63%), positive attitude, and good practice (68%) toward prevention of the disease. However, there were gaps in knowledge, with 78% of the respondents indicating eating without washing hands as the major cause of leptospirosis transmission. Our final model identified that higher knowledge score was associated with higher practice score. Our results indicate that it is important to increase knowledge, especially on transmission routes of leptospirosis, among visitors in recreational areas. Moreover, more attention needs to be paid to promote good practice habits among visitors, targeting those at higher risk of being infected by leptospirosis to prevent potential outbreaks in the recreational areas.
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