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Abstract Extracellular vesicles (EVs) are widely investigated for their implications in cell-cell signaling, immune modulation, disease pathogenesis, cancer, regenerative medicine, and as a potential drug delivery vector. However, maintaining integrity and bioactivity of EVs between Good Manufacturing Practice separation/filtration and end-user application remains a consistent bottleneck towards commercialization. Milk-derived extracellular vesicles (mEVs), separated from bovine milk, could provide a relatively low-cost, scalable platform for large-scale mEV production; however, the reliance on cold supply chain for storage remains a logistical and financial burden for biologics that are unstable at room temperature. Herein, we aim to characterize and engineer a freeze-dried, mEV formulation that can be stored at room temperature without sacrificing structure/bioactivity and can be reconstituted before delivery. In addition to undertaking established mEV assays of structure and function on our preparations, we introduce a novel, efficient, high throughput assay of mEV bioactivity based on Electric Cell Substrate Impedance Sensing (ECIS) in Human dermal fibroblast monolayers. By adding appropriate excipients, such as trehalose and tryptophan, we describe a protective formulation that preserves mEV bioactivity during long-term, room temperature storage. Our identification of the efficacy of tryptophan as a novel additive to mEV lyophilization solutions could represent a significant advancement in stabilizing small extracellular vesicles outside of cold storage conditions.

Abstract Objective The objective of this study is to assess disparities in adherence to swallowing therapy for clinically diagnosed oropharyngeal dysphagia (OD) patients. Methods Analysis was conducted on data from 600 patients with OD and confirmed impairments in swallowing safety and/or efficiency on a videofluoroscopic swallow study. Patients were classified based on their adherence to treatment sessions, defined as the number of swallow treatment sessions attended. The outcome of treatment adherence was categorized into two groups: those who attended fewer than 50% of the prescribed treatment sessions and those who attended 50% or more of the sessions. Continuous variables were presented as mean ± standard deviation or median ± interquartile range. Categorical variables were compared using Pearson chi‐square tests and Fisher's exact test when appropriate. Univariable and multivariable binary logistic regression models were employed to identify factors associated with successful adherence. Results Approximately 79% adhered to swallowing treatment. We found no significant relationship between adherence and age, sex, race, ethnicity, primary language, marital status, insurance status, occupation, median income, distance, education, OD severity, and diagnosis year (p > 0.05). We found no covariables to be significant predictors to swallowing treatment nonadherence in both univariable and multivariable binary regression models (p > 0.05). Conclusion The variables analyzed in this study were not significantly associated with nonadherence to swallow therapy. Nevertheless, our study still addressed an important knowledge gap and future studies would benefit from exploring other relevant socioeconomic and disease‐related factors. Level of evidence Level 4.

This study presents an analytical formulation to calculate the perturbed visibility function between two satellites. We begin with the representation of the visibility function in terms of the orbital elements of the two satellites up to the fourth order in eccentricity. Subsequently, the third-body perturbation on the satellite orbital elements is derived, leading to the construction of the perturbed visibility function in its final form. This technique is applicable to all eccentricities, altitudes, and perturbed satellite motions. Numerical simulations were conducted for select satellites at different altitudes with the visibility function perturbed by a third body, particularly the Earth's moon.

This article demonstrates how different cooling rates and precipitation hardening affected the mechanical properties of AA2024. Three impact test samples were chosen. Solution heat treatment was conducted at 500 °C for 2 hrs., followed by quenching in three different quenching media (Sunflower Oil, Sesame Oil, and Corn Oil). As a result, the Sunflower Oil showed the lowest shock absorption rate; hence, it was chosen as the quenching medium for this study. Consequently, all samples of tensile, hardness, and impact tests were solution heat treated at 500 °C for 2 hours, then quenched in Sunflower Oil to room temperature and artificially aged at temperatures of 180°C for 1,2,4 hour, 195°C for 1, 2, 4 hour, and 210°C for 1,2,4 hour. Considerable improvements in strength and hardness were observed while decreasing the ductility Due to the production of finely dispersed grains. Precipitation hardening at 180°C for 1 hour was the overall optimum achievement, which enhanced the UTS by 28.7% to 579 MPa, compared to the as-received sample with UTS 450 MPa. While annealing has reduced the UTS by 32.7% to 303 MPa.

Abstract Background Drug-resistant Tuberculosis (DR-TB) is a global health burden with high morbidity and mortality in developing countries including Egypt. The susceptibility to infection with DR-TB strains may be genetically determined. Several interleukin gene polymorphisms were investigated as risk factors for tuberculosis infection but focusing on their association with DR-TB was limited. Therefore, the objective of this study is to assess the association of IL 17 − 197 G > A (rs2275913) single nucleotide polymorphism (SNP) with susceptibility to DR-TB strains in comparison to drug-sensitive tuberculosis (DS-TB) strains in Egyptian patients with pulmonary TB. This cross-sectional study was conducted on 80 patients with DR-TB strains and 80 with DS-TB strains as a control group. Both age and sex were comparable among the study’s groups. IL-17 − 197 G > A (rs2275913) SNP was genotyped by real-time PCR, and IL-17 serum concentration was measured by enzyme-linked immunosorbent assay (ELISA). Results The GA and AA genotype frequencies of IL 17 − 197 G > A (rs2275913) SNP were significantly higher in patients with DR-TB strains than those with DS-TB strains (p A (rs2275913) resulted in higher serum levels of IL-17 and Egyptian patients with such polymorphism are three times at risk of infection with DR-TB strains than patients with wild type.

Abstract Introduction Polypharmacy is a growing phenomenon associated with adverse effects in older adults. We assessed the potential confounding effects of cumulative anticholinergic burden (ACB) in patients who were hospitalized with falls. Methods A noninterventional, prospective cohort study of unselected, acute admissions aged ≥ 65 years. Data were derived from electronic patient health records. Results were analyzed to determine the frequency of polypharmacy and degree of ACB and their relationship to falls risk. Primary outcomes were polypharmacy, defined as prescription of 5 or more regular oral medications, and ACB score. Key Results Four hundred eleven (411) consecutive subjects were included, mean age 83.8 ± 8.0 years: 40.6% men. There were 38.4% patients who were admitted with falls. Incidence of polypharmacy was 80.8%, (88.0% and 76.3% among those admitted with and without fall, respectively). Incidence of ACB score of 0, 1, 2, ≥ 3 was 38.7%, 20.9%, 14.6%, and 25.8%, respectively. On multivariate analysis, age [odds ratio (OR) = 1.030, 95% CI:1.000 ~ 1.050, P = 0.049], ACB score (OR = 1.150, 95% CI:1.020 ~ 1.290, P = 0.025), polypharmacy (OR = 2.140, 95% CI:1.190 ~ 3.870, P = 0.012), but not Charlson Comorbidity Index (OR = 0.920, 95% CI:0.810 ~ 1.040, P = 0.172) were significantly associated with higher falls rate. Of patients admitted with falls, 29.8% had drug‐related orthostatic hypotension, 24.7% had drug‐related bradycardia, 37.3% were prescribed centrally acting drugs, and 12.0% were taking inappropriate hypoglycemic agents. Conclusion Polypharmacy results in cumulative ACB and both are significantly associated with falls risk in older adults. The presence of polypharmacy and each unit rise in ACB score have a stronger effect of increasing falls risk compared to age and comorbidities.

Diet-induced obesity is implicated in the development of a variety of neurodegenerative disorders. Concurrently, the loss of mitochondrial Complex I protein or function is emerging as a key phenotype across an array of neurodegenerative disorders. Therefore, the objective of this study was to determine if Western diet (WD) feeding in swine [carbohydrate = 40.8% kCal (17.8% of total calories from high fructose corn syrup), protein = 16.2% kcal, fat = 42.9% kCal, and 2% cholesterol] would result in Complex I syndrome pathology. To characterize the effects of WD-induced obesity on brain mitochondria in swine, high resolution respirometry measurements from isolated brain mitochondria, oxidative phosphorylation Complex expression, and indices of oxidative stress and mitochondrial biogenesis were assessed in female Ossabaw swine fed a WD for 6-months. In line with Complex I syndrome, WD feeding severely reduced State 3 Complex I, State 3 Complex I and II, and uncoupled mitochondrial respiration in the hippocampus and prefrontal cortex (PFC). State 3 Complex I mitochondrial respiration in the PFC inversely correlated with serum total cholesterol. WD feeding also significantly reduced protein expression of oxidative phosphorylation Complexes I–V in the PFC. WD feeding significantly increased markers of antioxidant defense and mitochondrial biogenesis in the hippocampi and PFC. These data suggest WD-induced obesity may contribute to Complex I syndrome pathology by increasing oxidative stress, decreasing oxidative phosphorylation Complex protein expression, and reducing brain mitochondrial respiration. Furthermore, these findings provide mechanistic insight into the clinical link between obesity and mitochondrial Complex I related neurodegenerative disorders.

The (2 + 1)-dimensional Konopelchenko-Dubrovsky (KD) model and the modified version of the new Kudryashov (MVNK) technique are chosen in the current research to obtain the traveling wave solutions (TWSs). The obtained solutions represent the rich range of explicit solutions to the studied model. As a result, TWSs to the stated model are expressed as the different types of wave profiles such as the kink shape, bell shape, anti-bell shape, and W-shape wave profiles. The Hamiltonian function is found from the stated model and shown it as three dimensional, contour and phase plane in this manuscript. The effects of wave velocity and other parameters on the wave profile are also discussed. The obtained wave profiles are typically useful in applications how waves interact with high-dimensional systems in new, specialized structures. Additionally, the direction and position of solitons for changing other parameters can offer a clear-cut explanation of all the different features of wind and water waves. It is seen that the mentioned scheme is effective, potential and easy in mathematical physics. Finally, this study may be opened up brand-new avenues for further study and application in the fields of mathematical physics.

Abstract Background Recently, marked improvement of medical and surgical care for infants with congenital heart disease led to a growing population with a high risk of developmental delay. We aimed to identify developmental delay in these infants and its risk factors. So, we performed a cross-sectional study on 100 infants with congenital heart disease to assess their development by using Vineland Adaptive Behaviour Scale. We searched for risk factors for developmental delay in these infants. Correlations were conducted between the degree of developmental delay and the potential risk factors. To our knowledge, this study has not been conducted in developing countries before. Results The median age of the study group is 12.5 months, but it is equivalent to 9.5 months by using Vineland Adaptive Behaviour Scale. There was a statistically significant developmental delay in infants who had risk factors such as prematurity, history of neonatal intensive care unit admission, anemia, stunted growth, underweight, central cyanosis, or abnormal electroencephalographic. Conclusions Developmental delay is a common complication in infants with congenital heart disease. It has many risk factors; some of them could be modifiable as anemia, stunted growth, and underweight. Thus, early screening for developmental delay and its risk factors is of a great value. This could help in applying preventive measures and early intervention programs. Vineland Adaptive Behaviour Scale is a reliable tool in determination of developmental delay in infants with congenital heart disease.

Background and Aims: Acute pain management in drug addicts is a critical yet understudied topic. Drug addicts have a decreased pain threshold, impairing anaesthetic pain control. This study aimed to evaluate the postoperative quality of recovery in addicts and non-addicts after receiving erector spinae plane block (ESPB) with general anaesthesia. Methods: Sixty males, aged 18-60 years, with an American Society of Anesthesiologists physical status I/II, scheduled for elective lumbar decompression surgery, were divided into two equal groups. Group A included 30 addicts and group N included 30 non-addicts. Both groups received bilateral ultrasound-guided ESPB with 20 mL bupivacaine (0.25%) before induction of general anaesthesia. The primary outcome was comparison of the 24-hour postoperative quality of recovery (QoR-15) score. The secondary outcomes were time to first analgesic requirement, postoperative pain scores, morphine consumption, and adverse events. Results: The QoR-15 score was higher in group N (median = 128.5, interquartile range = 107-136) than in group A (118 [99-130]), indicating a better recovery in group N. The visual analogue scale pain score was lower in group N than in group A, especially in the first 12 hours postoperatively. Time to first analgesic request was significantly longer in group N than in group A (mean ± standard deviation: 8.67 ± 2.74 and 5.53 ± 1.64 hours, respectively, P =0.001), Morphine consumption was significantly higher in group A than in group N (9.62 ± 3.2 and 7.08 ± 2.57 mg, respectively, P =0.041). Conclusion: Drug addicts experienced decreased analgesic efficacy of ESPB compared to non-addicts, with comparable postoperative QoR-15 score following lumbar decompression surgery.

Abstract Cloud computing is utilised for information technology outsourcing of either industries or organisations. There are several inhibitors and motivations related factors to determine whether one can embrace the cloud services or not. Therefore, this paper presents a holistic and flexible cloud decision framework by taking a wide spectrum weighted factors related to the acceptance or denial of the cloud services. To have sustainable decision and obviating the shortcomings of the existing approaches on the cloud service adoption, a deep understanding of organisation's business process requirements and cost implications is required. To utilise the proposed model, the functional and non‐functional requirements associated to the business process of an adopter organisation must be specified. To reach a concrete decision, a hybrid approach is applied by incorporating the analytic hierarchy process and Delphi methods to prevent subjective outcomes and to have diverse experiences at the same time. To support the decision model, some economic theories and Moore law are used. To verify the proposed model, a Telecommunication Company is considered as a case study for its 6‐year plan of investment. The simulation results of conducted scenarios for the mentioned mid‐scale case study prove that it is logical to establish on‐premises a private datacenter and utilising the hybrid deployment once it encounters abrupt burst of resource demand. Altogether, the proposed holistic model can be customised for different users with different scales.

Nausea is a common disease symptom, yet there is no consensus regarding its physiological markers. In contrast, the process of vomiting is well documented as sequential muscular contractions of the diaphragm and abdominal muscles and esophageal shortening. Nausea, like other self-reported perceptions, is difficult to distinguish in preclinical models, but based on human experience emesis is usually preceded by nausea. Here we focused on measuring gastrointestinal and cardiorespiratory changes prior to emesis to provide additional insights into markers for nausea. Felines were instrumented to chronically record heart rate, respiration, and electromyographic (EMG) activity from the stomach and duodenum before and after intragastric delivery of saline or copper sulfate (CuSO4, from 83 to 322 mg). CuSO4 is a prototypical emetic test agent that triggers vomiting primarily by action on GI vagal afferent fibers when administered intragastrically. CuSO4 infusion elicited a significant increase in heart rate, decrease in respiratory rate, and a disruption of gastric and intestinal EMG activity several minutes prior to emesis. The change in EMG activity was most consistent in the duodenum. Administration of the same volume of saline did not induce these effects. Increasing the dose of CuSO4 did not alter the physiologic changes induced by the treatment. It is postulated that the intestinal EMG activity was related to the retrograde movement of chyme from the intestine to the stomach demonstrated to occur prior to emesis by other investigators. These findings suggest that monitoring of intestinal EMG activity, perhaps in combination with heart rate, may provide the best indicator of the onset of nausea following treatments and in disease conditions, including GI disease, associated with emesis.

Approximately 300,000 people in the United States are estimated to have Chagas’ disease, with cardiac manifestations including arrhythmias occurring in 20%–30% of patients. We report a patient diagnosed with Chagas’ cardiomyopathy after presenting in ventricular tachycardia. This patient was asymptomatic before her presentation with recurrent episodes of ventricular tachycardia, which motivated us to screen her since she was an immigrant from an endemic Chagas region. This manuscript highlights some of the characteristic cardiac magnetic resonance imaging (MRI) and electrophysiology findings present in patients with Chagas’ cardiomyopathy. We also detail the management of patients with Chagas’ cardiomyopathy who have suffered from ventricular tachycardia.

Introduction Little is known regarding how the risk of suicide in refugees relates to their host country. Specifically, to what extent, inter-country differences in structural factors between the host countries may explain the association between refugee status and subsequent suicide is lacking in previous literature. Objectives We aimed to investigate the risk of suicide among refugees in Sweden and Norway according to their sex, age, region/country of birth and duration of residence. Methods Each suicide case between the age of 18-64 years during 1998 and 2018 (17,572 and 9,443 cases in Sweden and Norway, respectively) was matched with up to 20 population-based controls, by sex and age. Multivariate-adjusted conditional logistic regression models yielding adjusted odds ratios (aORs) with 95% confidence intervals (95% CI) were used to test the association between refugee status and suicide. Results The aORs for suicide in refugees in Sweden and Norway were 0.5 (95% CI: 0.5-0.6) and 0.3 (95% CI: 0.3-0.4), compared with the Swedish-born and Norwegian-born individuals, respectively. Stratification by region/country of birth showed similar statistically significant lower odds for most refugee groups in both host countries except for refugees from Eritrea (aOR 1.0, 95% CI: 0.7-1.6) in Sweden. The risk of suicide did not vary much across refugee groups by their duration of residence, sex and age. Conclusions The findings of almost similar suicide mortality advantages among refugees in two host countries may suggest that resiliency and culture/religion-bound attitudes could be more influential for suicide risk among refugees than other post-migration environmental and structural factors in the host country. Disclosure No significant relationships.

Introduction Refugees, especially minors, who often have experienced traumatic events, are a vulnerable group regarding poor mental health. Little is known, however, of their risk of suicidal behaviour as young adults. Objectives We aimed to investigate the risk of suicidal behaviour for young adult refugees who migrated as minors. The moderating role of education and history of mental disorders in this association was also investigated. Methods In this register linkage study, all 19-30-year-old Swedish-born (n = 1,149,855) and refugees (n = 51,098) residing in Sweden on December 31st, 2009 were included. The follow-up period covered 2010-2016. Cox models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). The multivariate models were adjusted for socio-demographic, labour market marginalisation and health-related factors. Results Compared to Swedish-born, the risk of suicide attempt was lower for all refugees (HR 0.78, 95% CI 0.70-0.87), and accompanied refugee minors (HR 0.77, 95% CI 0.69-0.87), but estimates did not differ for unaccompanied refugee minors (HR 0.83, 95% CI 0.62-1.10). Low education and previous mental disorders increased the risk of suicide attempt in both refugees and Swedish-born, with lower excess risks in refugees. Findings for suicide were similar to those of suicide attempt. Conclusions Young adult refugees have a lower risk of suicidal behaviour than their Swedish-born peers, even if they have low educational level or have mental disorders. Young refugees who entered Sweden unaccompanied do not seem to be equally protected and need specific attention. Disclosure No significant relationships.

Twenty years have surpassed since the first vascularised composite allotransplantation (VCA) of the upper limb. This is an opportunity to reflect on the position of VCA as the gold standard in limb reconstruction. The paucity of recipients, tentative clinical outcomes, and insufficient scientific progress question whether VCA will remain a viable treatment option for the growing numbers of amputees. Bionic technology is advancing at a rapid pace. The prospect of widely available, affordable, safely applied prostheses with long-standing functional benefit is appealing. Progress in the field stems from the contributions made by engineering, electronic, computing and material science research groups. This review will address the ongoing reservations surrounding VCA whilst acknowledging the future impact of bionic technology as a realistic alternative for limb reconstruction.

Abstract Background There is evidence supporting a pathophysiological role of oxytocin in attention deficit hyperactive disorder (ADHD) especially hyperactive and combined subtypes. It is known that children with ADHD show a high rate of social cognitive problems regarding emotion recognition. Oxytocin was assumed to play a role in the emergence of social cognition deficits in ADHD. Aim of this study is to assess social cognition (emotion recognition) deficits in relation to oxytocin level in different subtypes of ADHD among the study group. Forty male patients with ADHD were recruited from psychiatric outpatient clinic of Fayoum University Hospital, were diagnosed according to DSM-5, and were assessed using Conner’s parent rating scale–revised (L). Social cognition measured by CANTAB emotion recognition task (ERT) and the level of salivary oxytocin was measured by ELISA technique. Results Combined subtype had been lower in correctly detecting the emotions of fear and anger. Predominately, hyperactive impulsive ADHD subtype was more rapid while detecting the emotions of surprise and disgust. There was significant negative correlation between age of onset of ADHD and errors in detecting the emotion of anger and positive correlation between age of onset of ADHD and errors in detecting the emotion of surprise. Correct detection of the emotion of happiness was associated with increased oxytocin level but the correct detection of the emotion of fear was inversely related to oxytocin level. No statistically significant difference between different subtypes of ADHD regarding salivary oxytocin level. Conclusion Oxytocin may play a role in social cognitive deficits in ADHD. The presence of social cognitive deficits in ADHD prompts further investigations to focus on the specificity of these deficits and in turn identify ways of managing them. Studying oxytocin in this population and its relation to social cognitive deficits can support the notion that oxytocin is a biological marker for ADHD.

Left ventricular (LV) catheterization provides LV pressure-volume (P-V) loops and it represents the gold standard for cardiac function monitoring. This technique, however, is invasive and this limits its applicability in clinical and in-home settings. Ballistocardiography (BCG) is a good candidate for non-invasive cardiac monitoring, as it is based on capturing non-invasively the body motion that results from the blood flowing through the cardiovascular system. This work aims at building a mechanistic connection between changes in the BCG signal, changes in the P-V loops and changes in cardiac function. A mechanism-driven model based on cardiovascular physiology has been used as a virtual laboratory to predict how changes in cardiac function will manifest in the BCG waveform. Specifically, model simulations indicate that a decline in LV contractility results in an increase of the relative timing between the ECG and BCG signal and a decrease in BCG amplitude. The predicted changes have subsequently been observed in measurements on three swine serving as pre-clinical models for pre- and post-myocardial infarction conditions. The reproducibility of BCG measurements has been assessed on repeated, consecutive sessions of data acquisitions on three additional swine. Overall, this study provides experimental evidence supporting the utilization of mechanism-driven mathematical modeling as a guide to interpret changes in the BCG signal on the basis of cardiovascular physiology, thereby advancing the BCG technique as an effective method for non-invasive monitoring of cardiac function.

Protein kinase A (PKA), which regulates a diverse set of biological functions downstream of cyclic AMP (cAMP), is a tetramer consisting of two catalytic subunits (PKA-C) and two regulatory subunits (PKA-R). When cAMP binds the PKA-R subunits, the PKA-C subunits are released and interact with downstream effectors. In Caenorhabditis elegans (C. elegans), PKA-C and PKA-R are encoded by kin-1 and kin-2, respectively. This review focuses on the contributions of work in C. elegans to our understanding of the many roles of PKA, including contractility and oocyte maturation in the reproductive system, lipid metabolism, physiology, mitochondrial function and lifespan, and a wide variety of behaviors. C. elegans provides a powerful genetic platform for understanding how this kinase can regulate an astounding variety of physiological responses.

Considerable evidence shows that the vestibular system contributes to adjusting sympathetic nervous system activity to maintain adequate blood pressure during movement and changes in posture. However, only a few prior experiments entailed recordings in conscious animals from brainstem neurons presumed to convey baroreceptor and vestibular inputs to neurons in the rostral ventrolateral medulla (RVLM) that provide inputs to sympathetic preganglionic neurons in the spinal cord. In this study, recordings were made in conscious felines from neurons in the medullary lateral tegmental field (LTF) and nucleus tractus solitarius (NTS) identified as regulating sympathetic nervous system activity by exhibiting changes in firing rate related to the cardiac cycle, or cardiac-related activity (CRA). Approximately 38% of LTF and NTS neurons responded to static 40° head up tilts with a change in firing rate (increase for 60% of the neurons, decrease for 40%) of ~50%. However, few of these neurons responded to 10° sinusoidal rotations in the pitch plane, in contrast to prior findings in decerebrate animals that the firing rates of both NTS and LTF neurons are modulated by small-amplitude body rotations. Thus, as previously demonstrated for RVLM neurons, in conscious animals NTS and LTF neurons only respond to large rotations that lead to changes in sympathetic nervous system activity. The similar responses to head-up rotations of LTF and NTS neurons with those documented for RVLM neurons suggest that LTF and NTS neurons are components of the vestibulo-sympathetic reflex pathway. However, a difference between NTS/LTF and RVLM neurons was variability in CRA over time. This variability was significantly greater for RVLM neurons, raising the hypothesis that the responsiveness of these neurons to baroreceptor input is adjusted based on the animal's vigilance and alertness.

The differential expression of two closelyassociated cyclooxygenase isozymes, COX-1 and COX-2, exhibited functions beyond eicosanoid metabolism. We hypothesized that COX-1 or COX-2 knockout lung fibroblasts may display altered protein profiles which may allow us to further differentiate the functional roles of these isozymes at the molecular level. Proteomic analysis shows constitutive production of macrophage migration inhibitory factor (MIF) in lung fibroblasts derived from COX-2−/− but not wild-type (WT) or COX-1−/− mice. MIF was spontaneously released in high levels into the extracellular milieu of COX2−/− fibroblasts seemingly from the preformed intracellular stores, with no change in the basal gene expression of MIF. The secretion and regulation of MIF in COX-2−/− was “prostaglandin-independent.” GO analysis showed that concurrent with upregulation of MIF, there is a significant surge in expression of genes related to fibroblast growth, FK506 binding proteins, and isomerase activity in COX-2−/− cells. Furthermore, COX-2−/− fibroblasts also exhibit a significant increase in transcriptional activity of various regulators, antagonists, and co-modulators of p53, as well as in the expression of oncogenes and related transcripts. Integrative Oncogenomics Cancer Browser (IntroGen) analysis shows downregulation of COX-2 and amplification of MIF and/or p53 activity during development of glioblastomas, ependymoma, and colon adenomas. These data indicate the functional role of the MIF-COX-p53 axis in inflammation and cancer at the genomic and proteomic levels in COX-2-ablated cells. This systematic analysis not only shows the proinflammatory state but also unveils a molecular signature of a pro-oncogenic state of COX-1 in COX-2 ablated cells.

Background: Unlike other chronic diseases, dementia caregiving is associated with enormous psychological burden, which stresses the need for caregivers-directed psychosocial interventions. Aim: This randomized controlled trial (RCT) was conducted to evaluate the short-term efficacy of a multi-component psychosocial intervention program for informal caregivers of persons with neurocognitive disorders in Alexandria, Egypt. Methods: Informal caregivers (120) were randomly assigned into intervention and control groups. The intervention group (60) participated in a multi-component program of 8 sessions, including psycho-education, group cognitive-behavioral therapy, and group social support. Program primary outcomes were assessed after program termination (post-1), and three months later (post-2). Measured outcomes included caregivers' knowledge, depression and anxiety symptoms, and perceived burden. Results: Caregivers' depression, anxiety, and perceived burden demonstrated significant drop at post-1, and post-2 compared to the control group (P< 0.001). The intervention group showed significant negative absolute change on depression, anxiety, and perceived burden measures, while on the dementia-related knowledge measure, a significant positive absolute change was found at post-1, and post-2 (P< 0.001), in comparison to controls. All outcome measures recorded a large effect size; the highest was for knowledge (partial eta2 = 0.98), and the least was for perceived burden (partial eta2 = 0.71). Conclusion: A multi-component psychosocial intervention for caregivers of persons with neurocognitive disorders demonstrated a short-term efficacy in reducing their burden, depression, and anxiety, as well as improving caregivers' knowledge. However, further research is needed to investigate long-term efficacy of the intervention.

Abstract Background To determine the occurrence of macular edema (ME) in vitreoretinal lymphoma (VRL). Methods Retrospective analysis of 17 patients (31 eyes) with VRL. A review of the literature was done as well. Results Nine patients (15 eyes) had fluorescein angiography and/or optical coherence tomography at presentation. In the ME group (six eyes of four patients), three patients (five eyes) had prior chemotherapy and radiation. Excluding eyes with radiation retinopathy (three eyes), rate of ME was 25% (3/12). When two unirradiated fellow eyes of eyes with radiation retinopathy were also excluded, ME rate was 10% (1/10). Excluding the eyes with intraocular surgery, the rate of ME was 0%. In the group without ME (nine eyes of six patients), one patient (one eye) was treated with chemotherapy and radiation and three patients (five eyes) with chemotherapy. Review of the literature showed that the ME was found between 2 and 60% of cases, but most of the cases with ME had prior interventions. Conclusions Macular edema in VRL is not uncommon but usually related to prior interventions. Macular edema as an initial presentation of VRL is rare.

Recently, integrated optics has become a functional platform for implementing machine learning algorithms and, in particular, neural networks. Photonic integrated circuits can straightforwardly perform vector-matrix multiplications with high efficiency and low power consumption by using weighting mechanism through linear optics. However, this cannot be said for the activation function, i.e., “threshold,” which requires either nonlinear optics or an electro-optic module with an appropriate dynamic range. Even though all-optical nonlinear optics is potentially faster, its current integration is challenging and is rather inefficient. Here, we demonstrate an electroabsorption modulator based on an indium tin oxide layer monolithically integrated into silicon photonic waveguides, whose dynamic range is used as a nonlinear activation function of a photonic neuron. The thresholding mechanism is based on a photodiode, which integrates the weighed products, and whose photovoltage drives the electroabsorption modulator. The synapse and neuron circuit is then constructed to execute a 200-node MNIST classification neural network used for benchmarking the nonlinear activation function and compared with an equivalent electronic module.

The constitutively-expressed cyclooxygenase 1 (COX-1) and the inducible COX-2 are both involved in the conversion of arachidonic acid (AA) to prostaglandins (PGs). However, the functional roles of COX-1 at the cellular level remain unclear. We hypothesized that by comparing differential gene expression and eicosanoid metabolism in lung fibroblasts from wild-type (WT) mice and COX-2-/- or COX-1-/- mice may help address the functional roles of COX-1 in inflammation and other cellular functions. Compared to WT, the number of specifically-induced transcripts were altered descendingly as follows: COX-2-/- > COX-1-/- > WT + IL-1β. COX-1-/- or COX-2-/- cells shared about 50% of the induced transcripts with WT cells treated with IL-1β, respectively. An interactive “anti-inflammatory, proinflammatory, and redox-activated” signature in the protein–protein interactome map was observed in COX-2-/- cells. The augmented COX-1 mRNA (in COX-2-/- cells) was associated with the upregulation of mRNAs for glutathione S-transferase (GST), superoxide dismutase (SOD), NAD(P)H dehydrogenase quinone 1 (NQO1), aryl hydrocarbon receptor (AhR), peroxiredoxin, phospholipase, prostacyclin synthase, and prostaglandin E synthase, resulting in a significant increase in the levels of PGE2, PGD2, leukotriene B4 (LTB4), PGF1α, thromboxane B2 (TXB2), and PGF2α. The COX-1 plays a dominant role in shifting AA toward the LTB4 pathway and anti-inflammatory activities. Compared to WT, the upregulated COX-1 mRNA in COX-2-/- cells generated an “eicosanoid storm”. The genomic characteristics of COX-2-/- is similar to that of proinflammatory cells as observed in IL-1β induced WT cells. COX-1-/- and COX-2-/- cells exhibited compensation of various eicosanoids at the genomic and metabolic levels.

End stage heart failure is a major cause of death in the US. At present, organ transplant and left-ventricular assist devices remain the only viable treatments for these patients. Cardiac tissue engineering presents the possibility of a new option. Nanomaterials such as gold nanorods (AuNRs) and carbon nanotubes (CNTs) present unique properties that are beneficial for cardiac tissue engineering approaches. In particular, these nanomaterials can modulate electrical conductivity, hardness, and roughness of bulk materials to improve tissue functionality. Moreover, they can deliver bioactive cargo to affect cell phenotypes. This review covers recent advances in the use of nanomaterials for cardiac tissue engineering.

Natural selection for specific functions places limits upon the amino acid substitutions a protein can accept. Mechanisms that expand the range of tolerable amino acid substitutions include chaperones that can rescue destabilized proteins and additional stability-enhancing substitutions. Here, we present an alternative mechanism that is simple and uses a frequently encountered network motif. Computational and experimental evidence shows that the self-correcting, negative-feedback gene regulation motif increases repressor expression in response to deleterious mutations and thereby precisely restores repression of a target gene. Furthermore, this ability to rescue repressor function is observable across the Eubacteria kingdom through the greater accumulation of amino acid substitutions in negative-feedback transcription factors compared to genes they control. We propose that negative feedback represents a self-contained genetic canalization mechanism that preserves phenotype while permitting access to a wider range of functional genotypes.

Chondrosarcoma of the spine is rare; it presents predominantly in very young males and presentation with neurological deficit is uncommon. Treatment of this type of tumour is mainly through surgery as adjuvant therapy is ineffective. En bloc resection of tumours in the spine are difficult although it remains the recommended treatment for chondrosarcoma. We report here presentation of a female with paresis (Frankel C) whom was diagnosed with a large chondrosarcoma of the T2 vertebra extending to the right upper thoracic cavity. The patient underwent radical excision through an anterior and posterior approach to the spine.

Artificial insemination represents one of technologies in livestock reproduction that can be applied to cattle, sheep, goats and other livestock. Application of livestock reproduction technology includes artificial insemination to increase reproductive efficiency. Semen processing is one critical phase in an artificial insemination program. The use of animal origin ingredient for semen extenders, such as egg yolk and milk, presents a risk of microbial contamination, which lead to the search for alternatives. To increase standard of quality, researchers exploits phyto-lesitin for semen extender and the results showed no significant differences in motility, viability, and acrosomal status of spermatozoa with phyto-lesitin extender when compared to tris-egg yolk-containing extenders. (Animal Production 9(1): 49-52 (2007) Key Words : Phyto-Lechitin, preservation, cryopreservation, semen

As synthetic analogs of the natural pigment melanin, polydopamine nanoparticles (NPs) are under active investigation as non-toxic anticancer photothermal agents and as free radical scavenging therapeutics. By analogy to the widely adopted polydopamine coatings, polydopamine NPs offer the potential for facile aqueous synthesis and incorporation of (bio)functional groups under mild temperature and pH conditions. However, clear procedures for the convenient and reproducible control of critical NP properties such as particle diameter, surface charge, and loading with functional molecules have yet to be established. In this work, we have synthesized polydopamine-based melanin-mimetic nanoparticles (MMNPs) with finely controlled diameters spanning ≈25 to 120 nm and report on the pH-dependence of zeta potential, methodologies for PEGylation, and the incorporation of fluorescent organic molecules. A comprehensive suite of complementary techniques, including dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM), X-ray photoelectron spectroscopy (XPS), zeta-potential, ultraviolet–visible (UV–Vis) absorption and fluorescence spectroscopy, and confocal microscopy, was used to characterize the MMNPs and their properties. Our PEGylated MMNPs are highly stable in both phosphate-buffered saline (PBS) and in cell culture media and exhibit no cytotoxicity up to at least 100 µg mL−1 concentrations. We also show that a post-functionalization methodology for fluorophore loading is especially suitable for producing MMNPs with stable fluorescence and significantly narrower emission profiles than previous reports, suggesting they will be useful for multimodal cell imaging. Our results pave the way towards biomedical imaging and possibly drug delivery applications, as well as fundamental studies of MMNP size and surface chemistry dependent cellular interactions.

Morphological characteristics of leaves, shoots and fruits of 5 brinjal varieties/lines viz., BL 099, BARI Brinjal-6, BL 117, BL 072 , BARI Brinjal-1 and wild Solanum torvum were studied at the experimental farm and laboratories of Bangabandhu Sheikh Mujibur Rahman Agricultural University (BSMRAU), Gazipur during the period from September 2004 to April 2005 in a randomized block design with three replications. Higher number of leaves (195.50 plant-1) inviteshigher shoot and fruit infestation which was found positively correlated (r2= 0.55). Higher leaf area (63.53cm2/leaf and leaf trichom (256.7/25mm2) had lower shoot and fruit infestation which was found negatively correlated (R2 =0.65). Among the morphological characteristics of shoots viz., number of shoot, daimeter and length of top inter node have a positive correlation (R2=0.69, 0.85, 0.44) and number of prickles and trichome on shoot have a negative correlation (R2 =0.22,0.70) with BSFB infestation on brinjal shoot. The morphological characters of fruits like fruit per plant, calyx length, fruit length, diameter, shape and color have significant effect on BSFB infestation. Diameter of fruit, weight of fruit has a positive correlation (R2=0.14, 0.10) and length of fruit (R2=0.36) and calyx (R2=0.79) have a negative effect on BSFB attacking brinjal fruit.

Anatomical characteristics of brinjal shoot and fruit of 5 resistance/susceptible brinjal varieties/lines viz. BL 099, BARI brinjal-6, BL 117, BL 072 , BARI brinjal -1 and wild Solanum torvum was studied at the experimental farm and Entomology laboratory of Bangabandhu Sheikh Mujibur Rahman Agricultural University (BSMRAU), Gazipur during the period from September 2004 to April 2005 in a randomized block design with three replications. From the observation it seem that resistant brinjal varieties (BL 099, BARI brinjal-6, BL 117, BL 072 , and wild Solanum torvum ) with thick cuticle, broad and thick collenchymataous area (8-9 layers), compact paranchyma cell, compact arrangement of vascular bundle and small pith area (1.67 mm) showed lower shoot infestation. Where as susceptible variety (BARI Brinjal-1) has thin cuticle and collenchymatous area (6-7 layers), loose pharanchyma cell, poorly develop vascular bundle and large pith area (3.47 mm). The thickness of pericarp and mesocarp were positively correlated (R2=0.64, 0.38) with the degree of fruit damage.The percent of fruit infestation decreases with the increases in number of seed per gram flesh of brinjal fruit. The variety having compact seed ring (BL009 and wild S.torvum with closely arranged seeds in mesocarp showed less infestation while variety with less compact seed ring with distantly arranged seed (BARI Brinjal-1) suffered more fruit infestation.

High-throughput Structural Genomics yields many new protein structures without known molecular function. This study aims to uncover these missing annotations by globally comparing select functional residues across the structural proteome. First, Evolutionary Trace Annotation, or ETA, identifies which proteins have local evolutionary and structural features in common; next, these proteins are linked together into a proteomic network of ETA similarities; then, starting from proteins with known functions, competing functional labels diffuse link-by-link over the entire network. Every node is thus assigned a likelihood z-score for every function, and the most significant one at each node wins and defines its annotation. In high-throughput controls, this competitive diffusion process recovered enzyme activity annotations with 99% and 97% accuracy at half-coverage for the third and fourth Enzyme Commission (EC) levels, respectively. This corresponds to false positive rates 4-fold lower than nearest-neighbor and 5-fold lower than sequence-based annotations. In practice, experimental validation of the predicted carboxylesterase activity in a protein from Staphylococcus aureus illustrated the effectiveness of this approach in the context of an increasingly drug-resistant microbe. This study further links molecular function to a small number of evolutionarily important residues recognizable by Evolutionary Tracing and it points to the specificity and sensitivity of functional annotation by competitive global network diffusion. A web server is at http://mammoth.bcm.tmc.edu/networks.

Peroxisome proliferators activated receptor-gamma2 (PPARγ2) represents the transcriptional master regulator of adipocyte differentiation and therefore has been suggested as a candidate gene for obesity, insulin resistance, and dyslipidemia. The objective of the study was to investigate for the first time the potential association of the most common variant Pro12Ala (p.P12A) substitution of the PPARγ2 gene with body mass index (BMI), blood pressure, fasting plasma glucose, plasma total cholesterol, LDL and HDL cholesterol, and plasma triglyceride in a sample of 202 (138 females and 64 male) type 2 diabetic Palestinians. Genotyping of the PPARγ2 p.P12A polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The A12 allele was associated with lower fasting plasma glucose (P=.03) but had no influence on blood pressure, BMI, or other metabolic parameters. In obese patients, the p.P12A substitution was associated with elevated total plasma cholesterol levels (P=.02) and a tendency toward increased LDL cholesterol level (P=.06). In conclusion, the p.P12A variant of the PPARγ2 may influence cardiovascular risk through effects on lipid metabolism in obese T2D Palestinian patients.

BACKGROUND: Pulmonary vein stenosis is a rare cause of pulmonary hypertension, with variable onset and presentation. One or more of the four pulmonary veins can be primarily or secondarily affected. A five-month-old girl presented with respiratory distress, lethargy and cyanosis requiring intubation.

Kawasaki disease is an acute multiorgan vasculitis occurs mostly in children between six months and five years of age. The etiology of the disease is unknown, but superantigens may have an important role in the pathogenesis. In this case report, a 10- year old boy is presented with signs of kawasaki disease and despite receiving two high doses intravenous immunoglobulin, cervical lymph nodes continued to enlarge and finally lymph node biopsy revealed angioimmunoblastic like T cell lymphoma. Because the etiology of Kawasaki disease is unknown, if lymphadenopathy persists, other diseases like lymphoma should be considered.