A Mechanism-Based Targeted Screen To Identify Epstein-Barr Virus-Directed Antiviral Agents.

Epstein-Barr virus (EBV) is one of nine human herpesviruses that persist latently to establish permanent residence in their hosts. Periodic activation into the lytic/replicative phase allows such viruses to propagate and spread, but can also cause disease in the host. This lytic phase is also essential for EBV to cause infectious mononucleosis and cancers, including B lymphocyte-derived Burkitt lymphoma and immunocompromise-associated lymphoproliferative diseases/lymphomas as well as epithelial cell-derived nasopharyngeal cell carcinoma. In the absence of anti-EBV agents, however, therapeutic options for EBV-related diseases are limited. In earlier work, we discovered that through the activities of the viral protein kinase conserved across herpesviruses and two cellular proteins, ATM and KAP1, a lytic cycle amplification loop is established, and disruption of this loop disables the EBV lytic cascade. We therefore devised a high-throughput screening assay, screened a small-molecule-compound library, and identified 17 candidates that impair the release of lytically replicated EBV. The identified compounds will (i) serve as lead compounds or may be modified to inhibit EBV and potentially other herpesviruses, and (ii) be developed into anticancer agents, as functions of KAP1 and ATM are tightly linked to cancer. Importantly, our screening strategy may also be used to screen additional compound libraries for antiherpesviral and anticancer drugs.IMPORTANCE Epstein-Barr virus, which is nearly ubiquitous in humans, is causal to infectious mononucleosis, chronic active EBV infection, and lymphoid and epithelial cancers. However, EBV-specific antiviral agents are not yet available. To aid in the identification of compounds that may be developed as antivirals, we pursued a mechanism-based approach. Since many of these diseases rely on EBV's lytic phase, we developed a high-throughput assay that is able to measure a key step that is essential for successful completion of EBV's lytic cascade. We used this assay to screen a library of small-molecule compounds and identified inhibitors that may be pursued for their anti-EBV and possibly even antiherpesviral potential, as this key mechanism appears to be common to several human herpesviruses. Given the prominent role of this mechanism in both herpesvirus biology and cancer, our screening assay may be used as a platform to identify both antiherpesviral and anticancer drugs.

The effect of education based on PEN-3 cultural model on students' menstrual health behaviors: a mixed method study.

Menstruation is a natural process in girls, but sometimes it is accompanied by beliefs and behaviors with cultural roots that result in poor health consequences; this study aimed to consider perceptions of individual, families and community to current cultural beliefs, and to determine the effect of education based on the PEN-3 cultural model on students' menstrual health behaviors in Iran. Study had a mixed method design. In the qualitative phase, data were collected from students, their mothers and teachers through focused group discussion and in-depth interviews. In the quantitative phase, training was done in four 2-h sessions for intervention group. The data were collected immediately and 2 months after the training by a questionnaire and they were analyzed by Friedman and Wilcoxon non-parametric tests. Training was effective on all of the model structures and significantly increased mean score of the health behavior after training and 2 months later by 8.74 and 13.86, respectively, in intervention group (P<0.05). The perception and behavior of the others and access to sanitary services and products, especially cultural factors affect girls'' menstrual health behaviors, therefore, it is necessary to design the health plans regarding each of these factors, and the cultural context of each community.

Pre-induction translabial ultrasound measurements in predicting mode of delivery compared to bishop score: a cross-sectional study.

BACKGROUND: By increased concerns about the accuracy of the traditional methods to predict outcomes after induction of labor, developing new standards has a great clinical importance. Here, we compared the predictive value of translabial ultrasound measurements with Bishop Score to determine the suitability of induction of labor. METHODS: A homogenous population of primigravid women was recruited. Induction of labor was performed with low-dose infusion of oxytocin. Translabial ultrasound and assessment of Bishop Score were performed by two different obstetricians. Receiver-operating characteristics curves were obtained to measure area under curve and subsequently, test sensitivity of each method. RESULTS: One hundred women entered the investigation. Maternal body mass index was significantly higher among candidates of Cesarean section (P: 0.02). Maternal age and fetus weight, gender and occiput position were not determinants of outcomes of induction of labor. Cervical length and fetal head-pubis symphysis distance measured by translabial ultrasound had a test sensitivity of 90 and 88 %, respectively which were slightly higher than sensitivity of Bishop score (84 %). CONCLUSION: This study demonstrates that translabial measurements can be a suitable alternative method to monitor labor progress with an admissible predictive value compared with Bishop Score. It is a non-invasive method which provides valuable objective measurements and can be better accepted by women when considering the painful process which is required in evaluating Bishop Score.

Comparative Evaluation of the Sedative and Analgesic Effects of Caudal Epidural Administration of Lidocaine Alone or in Combination With Xylazine, Detomidine, Medetomidine, and Dexmedetomidine in Mediterranean Miniature Donkeys.

The present study aimed to compare the sedative and analgesic effects of caudal epidural administration of lidocaine alone or in combination with four different α2-adrenergic agonists in Mediterranean miniature donkeys. A total of ten clinically healthy (five males and five females) Mediterranean miniature donkeys with an age of 5 ± 1 years, a weight of 100 ± 2 kg and a height at the withers of 0.8 ± 0.06 m (mean ± standard deviation) were used in experimental, crossover (Latin square), randomized, and blinded study. Animals were assigned to five treatment groups including lidocaine alone (0.22 mg kg-1), or associated with one among xylazine (0.17 mg kg-1), detomidine (30 µg kg-1), medetomidine (15 µg kg-1), dexmedetomidine (5 µg kg-1) with a minimum washout period of 8 days between treatments. The degree of sedation was investigated using a simple descriptive scale of 0-3. Sedation scores were compared at each time using nonparametric (Kruskal-Wallis and Mann-Whitney U) tests. Analgesia was assessed by pinprick test. Sedation was greater in lidocaine and/or α2-adrenergic agonist groups than in lidocaine group at 45-75 minutes after drug administration (P < .05). There were no significant differences among groups in time to onset of analgesia and ataxia and also in number of animals with complete perineal analgesia and ataxia. Duration of analgesia and ataxia were longer in lidocaine and/or α2-adrenergic agonist groups than in lidocaine (P < .05). There were no significant differences among lidocaine and/or α2-adrenergic agonist groups in sedation score and duration of analgesia and ataxia. No significant differences were observed in heart and respiratory rate and also rectal temperature at any time points between groups and within groups. Caudal epidural administration of α2- adrenergic agonists associated with lidocaine resulted in sedative effects on Mediterranean miniature donkeys, while lidocaine alone did not induce sedation. These drugs associations should be considered when superior analgesia is advocated.

The effects of ketamine-midazolam anesthesia on intraocular pressure in clinically normal dogs.

OBJECTIVE: To determine the effects of intravenous ketamine-midazolam anesthesia on intraocular pressure (IOP) in ocular normotensive dogs. ANIMALS: Thirteen adult mixed-breed dogs. PROCEDURES: Dogs were randomly assigned to treatment (n = 7) and control (n = 6) groups. Dogs in the treatment group received intravenous ketamine 15 mg/kg and midazolam 0.2 mg/kg and dogs in the control group received intravenous saline. The time of intravenous drug injection was recorded (T(0)). Measurements of IOP were then repeated 5 min (T(5)) and 20 min (T(20)) following the intravenous administration of ketamine-midazolam combination and saline in both groups. RESULTS: Measurements showed normal IOP values in both groups. The mean + or - SD baseline IOP values for treatment and control groups were 13.00 + or - 1.47 and 10.33 + or - 2.20, respectively. For baseline IOP values, there was no significant difference between treatment and control groups (P = 0.162). In the treatment group, the subsequent post-treatment mean + or - SD values were 15.64 + or - 2.17 (5 min), and 14.92 + or - 1.98 (20 min). There was no evidence of statistical difference between baseline values and post-treatment values after treatment with ketamine-midazolam (P(5) = 0.139; P(20) = 0.442). In control eyes, the mean + or - SD values at 5 and 20 min were 10.41 + or - 2.01 and 10.16 + or - 1.69, respectively. There was no significant difference between baseline values and post-treatment values in control group (P(5) = 1.000; P(20) = 1.000). CONCLUSION: Ketamine-midazolam combination has no clinically significant effect on IOP in the dog.

Prediction of membrane protein types by means of wavelet analysis and cascaded neural networks.

In this study, membrane proteins were classified using the information hidden in their sequences. It was achieved by applying the wavelet analysis to the sequences and consequently extracting several features, each of them revealing a proportion of the information content present in the sequence. The resultant features were made normalized and subsequently fed into a cascaded model developed in order to reduce the effect of the existing bias in the dataset, rising from the difference in size of the membrane protein classes. The results indicate an improvement in prediction accuracy of the model in comparison with similar works. The application of the presented model can be extended to other fields of structural biology due to its efficiency, simplicity and flexibility.

Agreement between Heart Failure Patients and Their Primary Caregivers on Symptom Assessment.

BACKGROUND: To decrease the readmission rate of heart failure (HF) patients, patients and their caregivers (CGs) should participate in symptoms assessment. This study aimed to assess the agreement between HF patients and their CGs on symptoms assessment. METHODS: Using a correlational design, 100 HF patients with their CGs (100 dyads) were recruited from Department of Cardiology, Iranshahr, during August-December 2014. Data were collected using modified Heart Failure Symptom Survey (HFSS).Pearson and intra-class correlation coefficients (ICC) were used to analyze the degree of agreement within HF dyads, using SPSS16. The level of significance was set at 0.05. RESULTS: The most frequent and severe symptom assessed equally by partners was shortness of breath (SOB). Dyads had a good agreement on assessment of extremity swelling (r=0.87, P≤0.01, ICC=0.861 CI: 0.798-0.901), SOB at rest (r=0.83, P≤0.01, ICC=0.775, CI: 0.680-0.845), SOB with activity (r=0.81, P≤0.01, ICC=0.795 CI: 0.711-0.858), and feeling depressed (r=0.77, P≤0.01, ICC=0.769, CI: 0.675-0.838). 28.6% of HF dyad had a good, 50% had a moderate, and 21.4 % had a poor agreement in assessment of HF symptoms. CONCLUSION: Most of the HF dyad members did not agree with each other on the assessment of symptoms. Knowledge, skills and ability of each dyad in HF symptoms assessment should be included in the patients' discharge planning and nurses must modify their misunderstanding or inability.

Evaluation the result of warm normal saline irrigation in ureteral endoscopic surgeries.

PURPOSE: Transurethral lithotripsy (TUL) is a major modality for the endoscopic management of ureteral stones. Ureteral spasm makes access for ureters difficult, which causes impaction of the ureteroscope, ureteral dislodge, and a low success rate of endoscopic surgeries. This study described the outcomes of a new endoscopic surgical experience by use of 40-degree warm saline irrigation during TUL compaired with routine ambient air irrigation in TUL. MATERIALS AND METHODS: In this randomized clinical trial from 2014 to 2015, 150 patients with ureteral stone with balanced randomization were divided into two parallel groups. Patients underwent TUL in the first group with 20-25 degree saline irrigation and in the second group with 40-degree saline irrigation. One surgical team with the same semi-rigid instrument performed all TULs and the other steps were similar in both groups. Complete stone fragmentation was measured as the primary outcome and the duration of procedure, retrograde stone migration and all and any intraoperative complications were the secondary measurements. RESULT: While comparing warm saline irrigation with cold saline irrigation, the rate of access to upper ureter was 95% versus 72%, stone retropulsion frequency was 10.7% versus 30.7% and the stone-free rate was 96% versus 76% respectively (P < .05). There was no ureteroscope impaction and ureteral dislodge in both groups. CONCLUSION: Using warm saline irrigation in endoscopic surgeries results in better surgical outcomes including a lower ureteral spasm rate, greater ureteral muscle relaxation and better access to the upper ureteral zone, and a lower rate of complications, such as ureteroscope impaction, ureteral dislodge and stone retropulsion.

Elderly peoples' experiences of nursing homes in Bam city: A qualitative study.

BACKGROUND: With the increasing number of elderly, especially in recent decades, transfer to nursing homes and the number of centers has also increased but experiences and problems of elders in these centers is less considered. So, the goal of this study is to explore the Elderly peoples' experiences of nursing homes. METHODS: The current research was performed using a phenomenological approach in 2016. Participation in the study is comprised of the elderly residents in a nursing home in Bam city who were selected based on an objective-oriented approach. The sampling was done until data saturation. Data collection methods were observation and an unstructured and in-depth interview. Data were analyzed using seven-stage Colaizzi process. RESULTS: In total, fifteen 68 - 82 years old people participated in our study and 52 primary and conceptual codes that were eventually categorized in five main themes (sense of rejection, sense of daily routine, impaired of communications, sense of hardship and mental obsession) and ten sub-themes emerged. CONCLUSION: Overall, most of the elders were not satisfied with the conditions. It seems that helpful, community and family education to acculturate respect for the elderly in the community, teach proper coping strategies, use the elderly's experiences, and consultation with them could be a way to maintain a sense of usefulness, independence and to prevent them from sensing monotonous and routine rhythm of life.

Retroperitoneal Fibrosis Due to Opium Abuse: A Case Series and Literature Review.

Retroperitoneal fibrosis (RPF) is a rare condition with an unclear etiology, presenting with the development of aberrant chronic nonspecific fibroinflammatory tissue in the retroperitoneal space, which can result in entrapment and obstruction of the retroperitoneal structures. RPF is a subtype of chronic periaortitis, and can be divided into two types: primary (or idiopathic) and secondary. RPF is usually idiopathic, but can also be secondary to malignancies, certain drugs, infections, surgery, and trauma. The systemic clinical manifestations are nonspecific and include low-grade fever, fatigue, anorexia, weight loss, and myalgia. We report five patients admitted to our hospital with clinical, laboratory, imaging, and pathologic findings compatible with RPF, and we describe their treatment and follow-up. We were suspicious that the impurities of some types of opium have an important role in the pathogenesis of RPF. Some of our patients used opium again after the follow-up period; however, they used a different type with a different origin, and we were surprised to see that RPF did not form again.

A combinatorial feature selection approach to describe the QSAR of dual site inhibitors of acetylcholinesterase.

Regarding the great potential of dual binding site inhibitors of acetylcholinesterase as the future potent drugs of Alzheimer's disease, this study was devoted to extraction of the most effective structural features of these inhibitors from among a large number of quantitative descriptors. To do this, we adopted a unique approach in quantitative structure-activity relationships. An efficient feature selection method was emphasized in such an approach, using the confirmative results of different routine and novel feature selection methods. The proposed methods generated quite consistent results ensuring the effectiveness of the selected structural features.

Analysis of factors that induce cysteine bonding state.

Regarding the fact that the protein structure is principally encoded in its sequence, investigating the bonding state of cysteine has gained a great deal of attention due to its significance in the formation of protein structure. Due to lack of evident influence of free cysteines on the protein structure, it may be expected that only half-cystines convey encoded information. The results obtained from the analysis of amino acid distribution in proximity of both states of cysteines explicitly indicated that perquisite information for inducing cysteine bonding state is present even in the flanking amino acid sequences of free cysteines.