Inclusivity of patients in early phase breast cancer clinical trials.

INTRODUCTION: Studies have shown that certain groups of patients are underrepresented in clinical trials including non-Caucasian ethnicity, poor fluency in English, low socioeconomic status, older age, neurodivergence, and large Body Mass Index (BMI). There is a need to ensure adequate representation of these groups so that the results of any trial accurately reflect the population. The aim of this study was to review the pathway of patients recruited into two early phase breast cancer clinical and determine the inclusivity of patients from the aforementioned sub-groups. METHODS: The Breast Cancer Research Database was reviewed, and the characteristics of all patients who were screened for eligibility in two early phase clinical trials was examined. The English Indices of Deprivation was used to populate the Index of Multiple Deprivation (IMD) for each patient using their postcode. RESULTS: In total, 392 patients were eligible to participate, between September 2020 to May 2023. Of these, 144 (36.7%) were recruited to these two trials. In all, 100% of patients eligible for these trials were approached and screened for participation. Eligible patients had a mean age of 53.5 years. Recruited patients were younger on average than those not recruited (49.1 years vs 56.0 years, p<0.0001). Only one recruited patient required an interpreter, compared with 24 (9.7%%) of those who were not recruited (p<0.001). There was no difference in the IMD (p=0.38), BMI (p=0.34) and neurodiversity (p=0.10) between patients recruited into clinical trials and those who were not. CONCLUSION: Older age and poor fluency in the English language remain barriers to participation in early-phase clinical trials despite implementing a clear pathway to trial recruitment. There is a pressing need to address these barriers by raising awareness, improve appropriate training and providing comprehensive trial information to patients in the language of their choice.

Thymoquinone' potent impairment of multidrug-resistant Staphylococcus aureus NorA efflux pump activity.

The drug efflux pump is a crucial mechanism implicated in resistance to multiple antimicrobials. Thymoquinone (TQ) has evidently demonstrated multiple activities, antibacterial being the most effective. Knowledge about TQ activity against multidrug-resistant Staphylococcus aureus is very scarce. Therefore, the present study was conducted to investigate TQ resistance modulation in ciprofloxacin (CIP) and doxycycline (DO) multidrug-resistant S. aureus. Forty-seven samples were collected from different sources, and S. aureus was isolated and identified. Then, S. aureus resistance profiles to antimicrobials, N. sativa essential oil, and TQ; the correlation between TQ-MIC readings and disc diffusion; cartwheel and ethidium bromide (EtBr) accumulation assays; and norA gene expression were all described within silico molecular docking for TQ interactions with norA efflux pump protein. TQ-MICs ranged from 5-320 µg/ml. TQ down-regulated norA gene expression, resulting in a drop in efflux pump activity of 77.5-90.6% in the examined strains, comparable to that observed with verapamil. Exposure of S. aureus strains to CIP and DO raises the initial basal efflux pumping expression to 34.2 and 22.9 times, respectively. This induced efflux pumping overexpression was substantially reduced by 97.7% when TQ was combined with CIP or DO. There was a significant reduction of MICs of CIP and DO MICs by 2-15 and 2-4 folds, respectively, after treatment with 0.5XMIC-TQ in resistance modulation assays. These results refer to TQ ligand inhibitory interactions with NorA protein in molecular docking. Interpretations of inhibition zone diameters (IZDs) of disc diffusion and TQ-MICs exhibit independence of MICs from IZDs, as indicated by invalid linear regression analysis. TQ significantly reduced efflux pumping S. aureus induced by CIP and DO, but further investigations are needed to improve TQ-pharmacokinetics to restore CIP and DO activity and suppress fluoroquinolone and doxycycline-resistant S. aureus selection in clinical and animal settings.

Comparing Left Ventricular Structure and Functions in End-Stage Renal Disease Using Conventional Echocardiography and 2D Speckle Tracking Echocardiography.

BACKGROUND: Patients on hemodialysis (HD) are prone to various cardiovascular complications. Two-dimensional speckle tracking echocardiography (2D STE) is an innovative technique for early myocardial dysfunction detection, even with normal ejection fraction (EF). OBJECTIVE: We aim to detect left ventricle (LV) dysfunction in regular hemodialysis patients using 2D STE compared to traditional echocardiography. METHODS: The study comprised 30 patients with end-stage renal disease (ESRD), subdivided according to left ventricular mass index (LVMI) into group 1 with left ventricular hypertrophy (LVH) (n=19) and group 2 without LVH (n=11). Another 30 healthy control subjects were recruited as group 3. The EF, average systolic velocity (Sa), and 2D LV strain were taken as measures of LV systolic function. The indicators for diastolic function included the E/A ratio and E velocity/peak early diastolic velocity. RESULTS: Regarding the parameters of LV systolic and diastolic functions assessed by traditional echocardiography, we found no significant difference between groups 1 and 2. However, using 2D STE, we observed significant differences in the average Sa velocity (p=0.025), average LV strain (p=0.03), 2D global longitudinal strain (GLS) (p=0.03), E/Ea (p=0.003), and LV myocardial performance index (MPI) (p=0.006). Also, a significant positive correlation was found between LVMI and left ventricular end-diastolic diameter (LVEDD) (p<0.01, r=0.63), EF measured by 2D (p=0.034, r=0.39), mitral E/A ratio (p=0.03, r=0.49), and mitral E/Ea (p<0.01, r=0.72). There was a significantly strong negative correlation between LVMI and 2D average LV strain (p=0.034, r=-0.39). CONCLUSION: We concluded that 2D STE is more sensitive than a conventional echo in detecting early LV systolic and diastolic dysfunction even in patients with normal EF.

Quercetin attenuated ischemic stroke induced neurodegeneration by modulating glutamatergic and synaptic signaling pathways.

Ischemic strokes originate whenever the circulation to the brain is interrupted, either temporarily or permanently, resulting in a lack of oxygen and other nutrients. This deprivation primarily impacts the cerebral cortex and striatum, resulting in neurodegeneration. Several experimental stroke models have demonstrated that the potent antioxidant quercetin offers protection against stroke-related damage. Multiple pathways have been associated with quercetin's ability to safeguard the brain from ischemic injury. This study examines whether the administration of quercetin alters glutamate NMDA and GluR1 receptor signaling in the cortex and striatum 72 h after transient middle cerebral artery occlusion. The administration of 10 mg/kg of quercetin shielded cortical and striatal neurons from cell death induced by ischemia in adult SD rats. Quercetin reversed the ischemia-induced reduction of NR2a/PSD95, consequently promoting the pro-survival AKT pathway and reducing CRMP2 phosphorylation. Additionally, quercetin decreased the levels of reactive oxygen species and inflammatory pathways while increasing the expression of the postsynaptic protein PSD95. Our results suggest that quercetin may be a promising neuroprotective drug for ischemic stroke therapy as it recovers neuronal damage via multiple pathways.

Seasonal variations of physiological responses, milk production, and fatty acid profile of local crossbred cows in Tunisia.

The study investigates the seasonal variations of physiological responses, milk yield, milk composition, and milk fatty acid profile of local crossbred cows (Friesian × Brown Atlas) in northwestern Tunisia. A total of 80 multiparous cows from smallholder farmers were sampled between 2018 and 2019. The cows were feed the same diet ad libitum and exposed to the same Mediterranean climatic conditions. Weekly rectal temperature (RT; °C), respiratory rate (RR; rpm), and heart rate (HR; bpm) were measured per cow in each season. Individual milk yield and samples were recorded bi-weekly and collected in duplicate for chemical analyses. Milk fatty acids (FAs) were analyzed using gas chromatography-mass spectrometry (GC-MS). Results showed an increase (P < 0.05) in RT (+ 1.3%), RR (+ 12.1%), and HR (+ 9.9%) when the temperature-humidity index (THI) increased from winter (53.6) to summer (74.4) in response to heat stress. Milk yield did not vary significantly between seasons (8.3 L/day on average). Summer milk contained more fat (+ 7.8%) and log SCC (+ 13.7%). The proportion of the monounsaturated (31.2 vs. 27.2%) and polyunsaturated (4.29 vs. 3.86%) FAs decreased (P < 0.05) between winter and summer. Saturated FAs (64.5 vs. 67.7%) were higher (P < 0.05) in summer than in winter. Winter milk fat contained higher levels of C18:2cis-9 trans-11 (CLA) (0.73 vs. 0.56%) and ω-3 FA (0.83 vs. 0.63%), but a lower ω-6/ω-3 ratio (4.07 vs. 6.17%) compared to summer. As the cows were fed the same diet throughout the two seasons, the performances obtained were mainly due to the resistance of the local crossbred cow to the hot conditions. It is concluded that the local crossbred cow maintains its productivity and tolerate the hot Mediterranean climate.

Nigella sativa-chitosan nanoparticles: Novel intestinal mucosal immunomodulator controls and protects against Salmonella enterica serovar Enteritidis infection in broilers.

BACKGROUND: Salmonella Enteritidis (SE) propagates in chickens' gastrointestinal surfaces and is transmitted to humans, causing food poisoning. Oral supplementation with natural nanoparticles can overcome the harsh gastrointestinal conditions facing oral vaccines and requires no antibiotic administration to protect against microbial infection. This study was designed to study Nigella sativa-chitosan nanoparticles (CNP-NS) prophylactic immunomodulatory efficacy against SE infection in broiler chicks. The CNP-NS was prepared and characterized, and its in vivo immunomodulatory activities against an avian virulent-MDR SE-induced challenge in chicks were investigated. RESULT: To verify the immune-protective activities of the CNP-NS, colony forming units (CFU) in the liver and fecal droppings; intestinal histopathological alterations and immune cell recruitment; MUC-2, TLR-4, cecal cytokines, and specific IgA gene expression levels were assessed. On the 7th and 12th days after the SE challenge, the CNP-NS supplemented chicks showed complete clearance of SE CFU in livers and fecal droppings, as well as an improvement in food conversion rate compared to non-supplemented CNP-NS that revealed the presence of the challenge SE CFU on the same days. A prominent influx of antigen presenting cells and lymphoid aggregates into the intestinal wall, spleen, and liver was detected with improvements in the intestinal villi morphometry of the CNP-NS-supplemented chicks. The changes of INF-γ, IL-1ß, and IL-4 cecal cytokines, as well as TLR-4, MUC-2, and IgA mRNA expression levels, confirm CNP-NS immunomodulatory activities and provide a mechanism(s) for its protective actions against the induced SE challenge of the tested chickens. CONCLUSION: These findings suggest promising useful insights into CNP-NS supplementation as a safe food additive for poultry meat consumers' and a protective immunomodulator of the chickens' mucosal immune systems. It could be recommended for epidemiological purposes to reduce the risk of SE food poisoning and transmission to humans.

The small molecule Erk1/2 signaling pathway inhibitor PD98059 improves DNA repair in an experimental autoimmune encephalomyelitis SJL/J mouse model of multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disorder in which the myelin sheath covering the central nervous system axons is damaged or lost, disrupting action potential conduction and leading to various neurological complications. The pathogenesis of MS remains unclear, and no effective therapies are currently available. MS is triggered by environmental factors in genetically susceptible individuals. DNA damage and DNA repair failure have been proposed as MS genetic risk factors; however, inconsistent evidence has been found in multiple studies. Therefore, more investigations are needed to ascertain whether DNA damage/repair is altered in this disorder. In this context, therapies that prevent DNA damage or enhance DNA repair could be effective strategies for MS treatment. The overactivation of the extracellular-signal-related kinase 1 and 2 (Erk1/2) pathway can lead to DNA damage and has been linked to MS pathogenesis. In our study, we observed substantially elevated oxidative DNA damage and slower DNA repair rates in an experimentally autoimmune encephalomyelitis animal model of MS (EAE). Moreover, statistical decreases in oxidative DNA strand breaks and faster repair rates were observed in EAE animals injected with the Erk1/2 inhibitor PD98059 (PD). Moreover, the expression of several genes associated with DNA strand breaks and repair changed in EAE mice at both the mRNA and protein levels, as revealed by the RT2 Profiler PCR array and verified by RT-PCR and protein analyses. The treatment with PD mitigated these changes and improved DNA repair gene expression. Our results demonstrate clear associations between Erk1/2 activation, DNA damage/repair, and MS pathology, and further suggest that PD therapy may be a promising adjuvant therapeutic strategy.

Assessment the impact of different fuels used in cement industry on pollutant emissions and ambient air quality: a case study in Egypt.

This study aims to assess the impact of using different fuels in Egyptian Titan Alexandria Portland Cement Company on emissions and concentrations of pollutants (Total suspended particles (TSP), nitrogen dioxide (NO2 ), and sulfur dioxide (SO2)) and their influence on ambient air quality during the period 2014-2020 using AERMOD dispersion model. The results showed that changing the fuel from natural gas in 2014 to coal mixed with alternative fuels (Tire-Derived Fuel (TDF), Dried Sewage Sludge (DSS), and Refuse Derived Fuels (RDF)) in 2015-2020 caused fluctuating variations in pollutant emissions and concentrations. The highest and lowest maximum concentrations of TSP occurred in 2017 and 2014 respectively, where the TSP is positively correlated with coal, RDF, and DSS and negatively correlated with natural gas, diesel, and TDF. Also, the lowest and highest maximum NO2 concentrations were detected in 2020 and 2016 followed by 2017 respectively, where NO2 is positively correlated with DSS and negatively correlated with TDF and varies with diesel, coal, and RDF. Moreover, the maximum concentrations of SO2 were the lowest in 2018 and highest in 2016 followed by 2017 because of its considerable positive correlation with natural gas and DSS and negative correlation with RDF, TDF, and coal. Generally, it was found that increasing the percentage of TDF and RDF with decreasing the percentage of DSS, diesel, and coal will reduce pollutant emissions and concentrations and enhance ambient air quality.

Nigella sativa Extract Potentially Inhibited Methicillin Resistant Staphylococcus aureus Induced Infection in Rabbits: Potential Immunomodulatory and Growth Promoting Properties.

Weaning is the most crucial period associated with increased stress and susceptibility to diseases in rabbits. Methicillin-resistant Staphylococcus aureus (MRSA), a historic emergent pathogen related to post weaning stressors, adversely affects rabbit's growth rate and productive cycle. Since MRSA is rapidly evolving antibiotics resistance, natural products are desperately required to tackle the public health threats posed by antimicrobial resistance. Thus, this study aimed to screen the iin vitro antibacterial activity of Nigella sativa extract (NSE) and its interactions with antibiotics against MRSA isolates. Moreover, 200 weaned rabbits were divided into 4 groups to investigate the iin vivo superiority of NSE graded levels towards growth performance, tight junction integrity, immune responsiveness and resistance against MRSA. Herein, NSE showed promising antimicrobial activities against MRSA isolates from animal (77.8%) and human (64.3%) origins. Additionally, MRSA isolates exposed to NSE became sensitive to all antimicrobials to which they were previously resistant. Our results described that the growth-promoting functions of NSE, especially at higher levels, were supported by elevated activities of digestive linked enzymes. Post-NSE feeding, rabbits' sera mediated bactericidal activities against MRSA. Notably, upregulated expression of occludin, CLDN-1, MUC-2 and JAM-2 genes was noted post NSE supplementation with maximum transcriptional levels in 500 mg/kg NSE fed group. Our data described that NSE constitutively motivated rabbits' immune responses and protected them against MRSA-induced experimental infection. Our results suggest the antimicrobial, growth stimulating and immunomodulation activities of NSE to maximize the capability of rabbits for disease response.

Adsorption of the Xanthan Gum Polymer and Sodium Dodecylbenzenesulfonate Surfactant in Sandstone Reservoirs: Experimental and Density Function Theory Studies.

Chemical flooding using a polymer and/or surfactant has been widely applied in oilfields worldwide for enhanced oil recovery. Chemical adsorption in reservoirs has a significant effect on the rock permeability and wettability and hence can affect the overall oil production. In this work, two chemicals, namely, the xanthan gum (XG) biopolymer and sodium dodecylbenzenesulfonate (SDBS) anionic surfactant, were used individually as displacement fluids. The amount of chemical adsorption on the rock surface and the residual resistance factor (permeability reduction) were calculated throughout the flooding experiments using an unconsolidated sandstone (SS) pack model. The effects of the injected chemicals' concentration and reservoir salinity on adsorption capacity have been examined. Additionally, the effect of the addition of nanosilica particles (NSPs) to the injected fluid on the rock adsorption was also investigated. The results showed that the amount of XG and SDBS adsorption on the rock surface increased, albeit to a different extent, by increasing the chemical concentration at the applied salinities (0, 3.5, 5, and 10%) of the displacement fluids. Also, the permeability reduction increased with the increase in XG and SDBS concentrations; however, permeability reduction due to SDBS flooding was lower than that of XG in SS. The use of NSPs as a coinjectant to the XG and SDBS displacement fluids increased the adsorption on the SS rock. A plausible mechanism for the adsorption of the XG/NSP and SDBS/NSP blends on the SS surface was proposed. A density function theory calculation was employed to establish a relation between the adsorptivity of NSPs on SDBS and XG and the total energy and dipole moment of the molecules.

[Pneumomediastinum and vomiting: Which approach to diagnosis? A case report]. / Pneumomédiastin et vomissements : quelle démarche diagnostique ? À propos d'un cas.

BACKGROUND: Spontaneous pneumomediastinum (SPM) is a rare and often unrecognized condition of which vomiting is one of the reported triggering factors. Differentiating SPM from Boerhaave's syndrome (pneumomediastinum secondary to esophageal breach) is the first step in management and prognosis. OBSERVATION: A 27-year-old woman with systemic lupus erythematous presented to the emergency department with epigastralgia, incoercible vomiting and diarrhoea. Abdominal CT showed circumferential thickening of the duodenum and bilateral ureteritis. Chest sections showed pneumomediastinum extending to the cervical region. Therapeutic management was based on prophylactic antibiotic therapy and an absolute diet (fasting). A CT scan with upper gastrointestinal opacification was performed to prevent esophageal rupture and showed quasi-obstructive thickening of the antral mucosa. The diagnosis was lupus enteritis and pneumomediastinum was secondary to the vomiting efforts. The patient was placed on corticosteroids and a favorable outcome ensued. CONCLUSION: Strenuous vomiting is one of the precipitating factors of SPM. Boerhaave's syndrome is the main differential diagnosis with a poor prognosis, unlike SPM, which has a good prognosis with conservative treatment.

Rasmussen aneurysm: A forgotten complication of tuberculosis in the COVID-19 era.

COVID-19 pandemic has led to an overwhelming healthcare system causing a delay in management of other infectious diseases such as tuberculosis. Rasmussen aneurysm (RA) appears in chronic cavitary tuberculosis. We report here, three cases of pulmonary tuberculosis complicated by RA admitted to Department 1 of Abderrahmane Mami hospital in Tunisia. Data were collected from June 2020 to September 2021. All patients presented with hemoptysis. Sputum was positive for the acid-fast bacilli. Computed tomographic pulmonary angiography showed RA. Only one patient underwent emergent glue embolization. These cases give an insight into the importance of timely therapeutic care for tuberculosis.

Nigella sativa oil extract: A natural novel specific conjugal transfer inhibitor of vancomycin resistance from vanA/B-resistant Enterococcus faecium to Staphylococcus aureus.

AIM: The emergence of vancomycin-resistant Staphylococcus aureus (VRSA) has been identified as one of the most challenging problems in healthcare settings worldwide. Specific conjugation inhibitors' development is critical in the fight against the spread of emerging VRSA. The impact of Nigella sativa oil on VR genes conjugal transfer from Enterococcus faecium (VREtfm) to vancomycin-sensitive S. aureus (VSSA) was investigated in this study. METHODS AND RESULTS: Enterococciwere isolated from retail broilers, fish, cows' milk, and human urine. VR E. faecalis and VREtfm VanA phenotypes were prevalent in retail broiler samples. The VREtfm isolates were dominant, exhibiting high levels of resistance to gentamycin and ciprofloxacin antibiotics, as well as the existence of both vanA and vanB genes and virulence traits (ESP+ , asa1+ ) as determined by PCR. Transconjugant VREtfm strains containing vanA/vabB and 20 kb plasmids (transfer frequency around 103 ) and carrying the Tn1546 transposon were identified. Tn1546 transposon transfer with its VR markers to VSSA was effectively inhibited in treated VREtfm donor strains with a sub-minimum inhibitory concentration of N. sativa oil. THE SIGNIFICANCE AND IMPACT OF THE STUDY: This work offers new insights for overcoming VR conjugal transfer utilizing natural N. sativa oil, as well as a suggestion for a novel specialized conjugation inhibitor that could effectively facilitate the difficulty of eliminating VR bacteria from healthcare settings.

Emerging advances and current applications of nanoMOF-based membranes for water treatment.

Metal-organic frameworks (MOFs) are significantly tunable materials that can be exploited in a wide range of applications. In recent years, a large number of studies have been focused on synthesizing nano-scale MOFs (nanoMOFs), thus taking advantage of these unique materials in various applications, especially those that are only possible at nano-scale. One of the technologies where nanoMOF materials occupy a central role is the membrane technology as one of the most efficient separation techniques. Therefore, numerous reports can be found on the enhancement of the physicochemical properties of polymeric membranes by using nanoMOFs, leading to remarkably improved performance. One of the most considerable applications of these nanoMOF-based membranes is in water treatment systems, because freshwater scarcity is now an undeniable crisis facing humanity. In this in-depth review, the most prominent synthesis and post-synthesis methods for the fabrication of nanoMOFs are initially discussed. Afterwards, different nanoMOF-based composite membranes such as thin-film nanocomposites (TFN) and mixed-matrix membranes (MMM) and their various fabrication methods are reviewed and compared. Then, the impacts of using MOFs-based membranes for water purification through growing metal-organic frameworks crystals on the support materials and utilization of metal-organic frameworks as fillers in mixed matrix membrane (MMM) are highlighted. Finally, a summary of pros and cons of using nanoMOFs in membrane technology for water treatment purposes and clear future prospects and research potentials are presented.

Prediction of the Rheological Properties of Invert Emulsion Mud Using an Artificial Neural Network.

Successful drilling operations require optimum well planning to overcome the challenges associated with geological and environmental constraints. One of the main well design programs is the mud program, which plays a crucial role in each drilling operation. Researchers focus on modeling the rheological properties of the drilling fluid seeking for accurate and real-time predictions that confirm its crucial potential as a research point. However, only substantial studies have real impact on the literature. Several AI-based models have been proposed for estimating mud rheological properties. However, most of them suffer from non-being field applicable attractive due to using non-readily field parameters as input variables. Some other studies have not provided a comprehensive description of the model to replicate or reproduce results using other datasets. In this study, two novel robust artificial neural network (ANN) models for estimating invert emulsion mud plastic viscosity and yield point have been developed using actual field data based on 407 datasets. These datasets include mud plastic viscosity (PV), yield point (YP), mud temperature (T), marsh funnel viscosity (MF), and solid content. The mathematical base of each model has been provided to provide a clear means for models' replicability. Results of the evaluation criteria depicted the outstanding performance and consistency of the proposed models over extant ANN models and empirical correlations. Statistical evaluation revealed that the plastic viscosity ANN model has a coefficient of determination (R 2) of 98.82%, a root-mean-square error (RMSE) of 1.37, an average relative error (ARE) of 0.12, and an absolute average relative error of 2.69, while for yield point, this model has a coefficient of determination (R 2) of 94%, a root-mean-square error (RMSE) of 0.76, an average relative error (ARE) of -0.67, and an absolute average relative error of 3.18.

Huffmanela sp. (Nematoda: Trichosomoididae: Huffmanelinae) Encountered in the Whitecheek Shark (Carcharhinus Dussumieri) in The Arabian Gulf.

Veterinary inspection of fish caught at the western side of the Arabian Gulf off the shore of Saudi Arabia in 2017 revealed abnormal irregular zigzag black lines in the skins of 135 out of 1500 (prevalence = 9 %) whitecheek sharks (Carcharhinus dussumieri). These lesions have been noticed in the dorsal and ventral part of the head near the snout and around the eyes, as well as in the skin of the pectoral fins. The parasitological, pathological and ultramorphological aspects of the sampled fish were studied using a light microscope, as well as scanning and transmission electron microscopes. Trichosomoidid-type eggs identified as Huffmanela sp. were found in the superficial layer of the skin. The mature eggs containing larvae (n = 75) were ellipsoidal or spindle-shaped, smooth-shelled, amber-brown to dark brown or even black in colour. The width of the eggs ranged from 34 to 49µm with lengths ranging from 95 to 107µm. The polar plugs of the immature eggs were slightly protruding, whereas mature eggs had clearly protruding polar plugs. The width of the polar plugs ranged from 4.5 - 9.5µm. The shells of the eggs were smooth and there was a thin layer seen near the polar areas. The infected skin exhibited desquamated epithelium, with inflammatory cell aggregations and melanophores in the debris. The underlying musculatures of the skin were free from any eggs, but showed mild pathological changes, including congestion of blood vessels, haemorrhages and oedema. The prevalence of infection showed seasonality, peaking significantly in the spring (18.18 %), with comparable prevalence rates in winter and summer (9.43 % and 8.57 %, respectively). However, infections dropped significantly during the autumn months (3.75 %). It is believed that this is the first study reporting the presence of Huffmanela sp. in whitecheek sharks at El-Jubail Province, Saudi Arabia, Arabian Gulf.

Isolated Persistent Left Superior Vena Cava Revealed by an Associated Asthma.

BACKGROUND: Persistent left superior vena cava (PLSVC) is a rare anomaly of the thoracic venous system. Case Report. We present a case of a patient with isolated asymptomatic PLSVC, who was diagnosed because of dyspnea revealing an associated asthma. An 18-year-old male patient complained of paroxystic sibilant dyspnea. He did not have any anomaly in physical examination. The chest X-ray revealed cardiomegaly with a widening of lower mediastinum. The electrocardiogram does not show any anomaly. Echocardiography showed the PLSVC. The thoracic contrast computed tomography of the chest showed ecstasies of the right cardiac cavities and a double superior vena cava. The patient did not have similar family cases. Respiratory functional explorations led to the diagnosis of an associated asthma. Currently, he is followed up periodically. Asthma was improved with inhaled corticosteroid treatment. CONCLUSION: PLSVC is rare but can have important clinical implications. Associated severe cardiac malformations must be systematically sought.

The role of the circadian clock in cancer hallmark acquisition and immune-based cancer therapeutics.

The circadian system temporally regulates physiology to maintain homeostasis. Co-opting and disrupting circadian signals appear to be distinct attributes that are functionally important for the development of a tumor and can enable or give rise to the hallmarks that tumors use to facilitate their initiation, growth and progression. Because circadian signals are also strong regulators of immune cell proliferation, trafficking and exhaustion states, they play a role in how tumors respond to immune-based cancer therapeutics. While immuno-oncology has heralded a paradigm shift in cancer therapeutics, greater accuracy is needed to increase our capability of predicting who will respond favorably to, or who is likely to experience the troubling adverse effects of, immunotherapy. Insights into circadian signals may further refine our understanding of biological determinants of response and help answer the fundamental question of whether certain perturbations in circadian signals interfere with the activity of immune checkpoint inhibitors. Here we review the body of literature highlighting circadian disruption as a cancer promoter and synthesize the burgeoning evidence suggesting circadian signals play a role in how tumors respond to immune-based anti-cancer therapeutics. The goal is to develop a framework to advance our understanding of the relationships between circadian markers, cancer biology, and immunotherapeutics. Bolstered by this new understanding, these relationships may then be pursued in future clinical studies to improve our ability to predict which patients will respond favorably to, and avoid the adverse effects of, traditional and immune-based cancer therapeutics.

Validation of a novel UPLC-MS/MS method for estimation of metformin and empagliflozin simultaneously in human plasma using freezing lipid precipitation approach and its application to pharmacokinetic study.

A fast, sensitive one step UPLC ESI-MS/MS method was successfully applied for the simultaneous estimation of two concurrently administrated antidiabetic drugs, Metformin (MET) and Empagliflozin (EMPA) in human plasma. Metformin-d6 (MET-d6) and Empagliflozin-d4 (EMPA-d4) were utilized as internal standards. Extraction of the analytes from the human plasma was performed through acetonitrile precipitation technique followed by freezing the precipitated plasma proteins and lipids to minimize the matrix effect. Chromatographic analysis was developed on Acquity UPLC BEH C18 column (1.7 µm, 2.1 × 50 mm) using isocratic elution mode. A mobile phase of formic acid (0.01 %): acetonitrile (70:30 v/v) with a flow rate of 0.3 mL/min achieved optimum separation. Multiple reaction monitoring (MRM) in positive ion mode, with transitions at (m/z) 130.14 →71.08 for (MET), 451.72 →71.29 for (EMPA), 136.03 →77.02 for (MET-d6), and 455.43 → 75.05 for (EMPA-d4) was used for quantification. The obtained linearity covered the concentration ranges of 10-1500 ng/mL and 2.0-250.0 ng/mL for MET and EMPA, respectively. The run time of the proposed Method didn't exceed 3.0 min allowing faster analysis and determination of larger number of samples per day without affecting accuracy and sensitivity. The presented chromatographic method could be successfully applied in pharmacokinetics studies and therapeutic monitoring of MET and EMPA in patients' plasma administrating fixed dose combination of both drug with high reproducibility and ruggedness.