Early post-operative outcomes of robot-assisted pyeloplasty in patients with unilateral ureteropelvic junction obstruction.

INTRODUCTION: Ureteropelvic junction obstruction (UPJO) is a commonly encountered abnormality and it can lead to serious consequences such as renal dysplasia eventually resulting in loss of kidney. Hence, early diagnosis and timely management remains the cornerstone of the treatment. The most anticipated technique amongst modern day urologist is the robot-assisted laparoscopic pyeloplasty (RALP). The study aims to determine early post-operative outcomes of robot-assisted laparoscopic transperitoneal pyeloplasty procedure in patients presenting with unilateral ureteropelvic junction obstruction to establish the local perspective. METHODOLOGY: This is a descriptive study involving patients with ureteropelvic junction obstruction in a tertiary care facility in Karachi; Sindh Institute of Urology and Transplant (SIUT). A total of 46 participants were recruited. Robot-assisted laparoscopic transperitoneal dismembered Hynes-Anderson pyeloplasty was performed by a single surgeon with over 3 years of experience in the presence of the researcher. Early postoperative outcome total operative time, length of hospital stay, console time and blood loss were noted by the researcher as per operational definition. Data were analyzed on SPSS Version 22. RESULTS: Mean age in our study was 46.51 years with the standard deviation of ± 10.87. Whereas, mean length of hospital stay, total operative time, total blood loss, console time, pre-hemoglobin, posthemoglobin, height, weight and BMI in our study was 1.19 ± 0.40 days, 64.58 ± 17.59 min, 9.56 ± 6.13 ml, 30.17 ± 4.99 min, 12.66 ± 1.47 ml, 11.79 ± 1.93 ml, 165.62 ± 8.23 cm, 68.34 ± 8.23 kg and 24.85 ± 3.34 kg/m2, respectively. CONCLUSION: Recent advancements in technology have yielded the latest RALP technique which has been proven significantly better than existing approaches and similar results are reported by this study demonstrating improvement in peri-operative and post-operative outcomes ultimately ameliorating the quality of life of patients with UPJO.

Synthesis of a Novel Gold(I) Complex and Evaluation of Its Anticancer Properties in Breast Cancer Cells.

BACKGROUND: Platinum complexes are commonly used for cancer chemotherapy; however, they are not only highly-priced but also have various side effects. It is, therefore, important to design affordable anticancer drugs with minimal side effects. METHODS: We synthesized a new gold(I) complex, PF6{(BDPEA)(TPPMS) digold(I)} (abbreviated as PBTDG) and tested its cytotoxicity in MCF-7 breast cancer cells. We also evaluated the effects of PBTDG on mitochondrial membrane potential, generation of reactive oxygen species (ROS) and apoptosis in breast cancer cells. RESULTS: The IC50 values for PBTDG and sorafenib were found to be 1.48 µM and 4.45 µM, respectively. Exposure to PBTDG caused significant and concentration-dependent depletion of ATP and disruption of mitochondrial membrane potential. PBTDG induced 2.6, 3.6, and 5.7-fold apoptosis for 1 µM, 3 µM, and 10 µM concentrations, respectively. The induction of apoptosis by the same concentrations of sorafenib was 1.2, 1.3, and 1.6-fold, respectively. The low concentration of PBTDG (1 µM) induced the generation of ROS by 99.83%, which was significantly higher than the ROS generation caused by the same concentration of sorafenib (73.76%). The ROS induction caused by higher concentrations (5 µM) of PBTDG and sorafenib were 104.95% and 122.11%, respectively. CONCLUSION: The lower concentration of PBTDG produced similar cytotoxicity and apoptotic effects that were caused by a comparatively higher concentration of known anticancer drug (sorafenib). The anticancer effects of PBTDG are attributed to its tendency to disrupt mitochondrial membrane potential, induction of apoptosis and generation of ROS. Further studies are warranted to test the anticancer effects of PBTDG in animal models of cancer.

Facile synthesis and anion binding studies of fluorescein/benzo-12-crown-4 ether based bis-dipyrromethane (DPM) receptors.

Two novel fluorescein as well as benzo-12-crown-4 ether functionalized dipyrromethane receptors (DPM3 and DPM4) have successfully been synthesized. The anion (used as their TBA salts) binding studies of thus prepared DPM3 and DPM4 receptors were evaluated by the UV-visible spectrophotometric titrations. Binding affinities as well as the stoichiometry were determined through the UV-visible titrations data with the involvement of the BindFit (v0.5) package available online at https://supramolecular.org. Moreover, binding events were validated by means of the comparison of the partial 1H-NMR spectrum of the simple host molecule with that of the host-guest complex, and the 1 : 1 stoichiometry were further confirmed by the Job's method of continuous variation. From the results, we observed the binding constant (Ka) values of DPM3/DPM4 with various tested anions in the range of 516.07 M-1 to 63789.81 M-1, depending upon the nature/shape/size of the anions. Moreover, the anion-π interactions were confirmed by the partial 1H-NMR spectral data, and further supported by the literature reported systems. The authors hope that such types of valued receptors will be benefitted in future for the recognizing/binding of a variety of biologically important anions.

Explorations of CRISPR/Cas9 for improving the long-term efficacy of universal CAR-T cells in tumor immunotherapy.

Chimeric antigen receptor (CAR) T therapy has shown remarkable success in discovering novel CAR-T cell products for treating malignancies. Despite of successful results from clinical trials, CAR-T cell therapy is ineffective for long-term disease progression. Numerous challenges of CAR-T cell immunotherapy such as cell dysfunction, cytokine-related toxicities, TGF-ß resistance, GvHD risks, antigen escape, restricted trafficking, and tumor cell infiltration still exist that hamper the safety and efficacy of CAR-T cells for malignancies. The accumulated data revealed that these challenges could be overcome with the advanced CRISPR genome editing technology, which is the most promising tool to knockout TRAC and HLA genes, inhibiting the effects of dominant negative receptors (PD-1, TGF-ß, and B2M), lowering the risks of cytokine release syndrome (CRS), and regulating CAR-T cell function in the tumor microenvironment (TME). CRISPR technology employs DSB-free genome editing methods that robustly allow efficient and controllable genetic modification. The present review explored the innovative aspects of CRISPR/Cas9 technology for developing next-generation/universal allogeneic CAR-T cells. The present manuscript addressed the ongoing status of clinical trials of CRISPR/Cas9-engineered CAR-T cells against cancer and pointed out the off-target effects associated with CRISPR/Cas9 genome editing. It is concluded that CAR-T cells modified by CRISPR/Cas9 significantly improved antitumor efficacy in a cost-effective manner that provides opportunities for novel cancer immunotherapies.

An automated machine learning tool for breast cancer diagnosis for healthcare professionals.

The paper proposes a hybrid metaheuristic algorithm known as harmony search and simulated annealing (HS-SA) for accurate and precise breast malignancy disclosure by integrating harmony search (HS) and simulated annealing (SA) optimisation methods. An enhanced wavelet-based contourlet transform (WBCT) procedure for mining the highlights of the region of interest (ROI) is explored, that allows execution upgradation over other standard procedures. The anticipated HS-SA algorithm aims to reduce the feature dimensions and assemble at the unparalleled optimal feature subset. The SVM classifier fed with the picke.d feature subsets and assisted by varied kernel functions upheld its classification capacities in contrast with the conformist machine learning classification and optimisation methods. The portrayed computer-aided diagnosis (CAD) model is confronted by evaluating its learning capability on two different breast mammographic datasets i) benchmark BCDR-F03 dataset and ii) local mammographic dataset. Preliminary propagations, experimental outcomes, and quantifiable assessments likewise demonstrate that the proposed model is pragmatic and favourable for the automated breast malignancy findings with optimal performance and fewer overheads. The discoveries show that the proposed CAD system (HS-SA+Kernel SVM) is superior to various characterisation accuracy techniques with an accuracy of 99.89% for the local mammographic dataset and 99.76% for benchmark BCDR-F03 dataset, AUC of 99.41% for the local mammographic dataset and 99.21% for reference BCDR-F03 dataset while keeping the element space restricted to only seven feature subsets and computational prerequisites as low as is judicious.

Applicability of modified weibull extension distribution in modeling censored medical datasets: a bayesian perspective.

There are some contributions analyzing the censored medical datasets using modifications of the conventional lifetime distribution; however most of the said contributions did not considered the modification of the Weibull distribution (WD). The WD is an important lifetime model. Due to its prime importance in modeling life data, many researchers have proposed different modifications of WD. One of the most recent modifications of WD is Modified Weibull Extension distribution (MWED). However, the ability of MWED to model the censored medical data has not yet been explored in the literature. We have explored the suitability of the model in modeling censored medical datasets. The analysis has been carried out using Bayesian methods under different loss functions and informative priors. The approximate Bayes estimates have been computed using Lindley's approximation. Based on detailed simulation study and real life analysis, it has been concluded that Bayesian methods performed better as compared to maximum likelihood estimates. In case of small samples, the performance of Bayes estimates under ELF and informative prior was the best. However, in case of large samples, the choice of prior and loss function did not affect the efficiency of the results to a large extend. The MWED performed efficiently in modeling real censored datasets relating to survival times of the leukemia and bile duct cancer patients. The MWED was explored to be a very promising candidate model for modeling censored medical datasets.

Efficacy of Natural Formulation Containing Activated Charcoal, Calcium Sennosides, Peppermint Oil, Fennel Oil, Rhubarb Extract, and Purified Sulfur (Nucarb®) in Relieving Constipation.

Introduction Long-term use of laxatives may have side effects such as bloating, allergic reaction, abdominal pain, metabolic disturbances, and hepatotoxicity. In this study, we have compared the efficacy of herbal medicine Nucarb, a combination of activated charcoal, calcium sennosides, peppermint oil, fennel oil, rhubarb extract, and purified sulfur, in relieving constipation. Methods This longitudinal study was conducted in multiple cities of Pakistan from April 2021 to June 2021. A total of 1000 patients, of either gender between age group 18 and 75 years, with complete spontaneous bowel movement of less than or equal to two times per week, were enrolled in the study. Participants were prescribed two tablets of Nucarb once daily (OD) at bedtime for the first seven days, followed by one tablet of Nucarb OD at bedtime for the following seven days. They were asked to return for follow-up after 14 days. Results There was a statistically significant improvement in all six components of constipation. After 14 days, the severity of constipation reduced by 80.70%, the sensation of straining was reduced by 72.69%, and the feeling of incomplete evacuation was reduced by 71.87%. There was no adverse event reported. Conclusion Nucarb is efficacious in reducing the severity of constipation, sensation of straining, bloating and abdominal pain, feeling of incomplete evacuation, and difficulty in passing gas. Since it is a herbal product, it can be safely used in all populations.

COVID-19-related sudden sensorineural hearing loss.

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) can be a feature of COVID-19. It may present alone or with other symptoms of the disease. However, there is little written in the literature about its occurrence. We aimed to evaluate the socio-clinical characteristics and outcome of confirmed mild- to moderate COVID-19 cases with SSNHL in Tikrit city, Iraq. MATERIALS AND METHODS: This descriptive study was conducted at the Otolaryngology Department, Tikrit General Hospital, Tikrit city, Iraq. The period of the study was from December 1, 2020 to June 30, 2021.Mild and moderate COVID-19 subjects confirmed by real-time polymerase reaction were included in the study. Detailed demographic (age, gender, and smoking habit) and clinical characteristics (onset and duration of deafness, side, severity, associated ear, nose, and throat symptoms, and comorbidity) were recorded for every patient. Outcomes following the steroid treatment protocol were also registered. RESULTS: SSNHL was identified in 26 patients, of whom 20 (76.9%) were women, 20 (76.9%) were in the age group ≥ 30 years, and 21 (80.8%) were non-smokers. Around three-quarters of the subjects were identified within the first week of deafness occurrence. Bilateral (18/26) was more common than unilateral deafness (8/26); therefore, the total number of deaf ears was 44. Besides, bilateral symmetrical deafness (13/18) outnumbered the asymmetrical type (5/18). Around three-quarters were of moderate severity. The most common otological symptom was tinnitus (25/26). The most common nose and throat symptom was anosmia (6/26). The mean hearing threshold before and after treatment with oral steroids ± intratympanic steroids was 50.91 ± 11.777 dB and 40.24 ± 15.693, respectively. One patient with bilateral SSNHL was lost to follow-up; the remaining number of deaf ears was 42, and half of them were partially improved. The outcome of the treatment showed no statistically significant relation with the duration, side, and severity of SSNHL (p>0.05). CONCLUSION: The majority of COVID-19-related SSNHL cases presented within one week of onset, with bilateral outnumbering unilateral cases. Tinnitus was the most common associated symptom. Treatment with steroids achieved partial improvement in half of the cases, and this outcome was not affected by the duration, side, and severity of deafness.

Synthesis of biologically active fused 1,4-oxathiin derivatives from 4-hydroxydithiocoumarins, arylacetylenes and dimethyl sulfoxide by Cu(i)-catalyzed C-H functionalization and cross-dehydrogenative C-S coupling reactions.

The hitherto unreported 2-aryl-10H-thiochromeno[3,2-b][1,4]oxathiin-10-one derivatives are obtained in a single pot from 4-hydroxydithiocoumarins, arylacetylenes and dimethyl sulfoxide in the presence of 10 mol% CuI and K2CO3 in an oil bath at 70 °C. The novelties of the present protocol are (i) selective C-H functionalization at the C-3 position of 4-hydroxydithiocoumarin, (ii) regioselective hydrothiolation with arylacetylenes and (iii) concomitant cyclisation. The major advantages are mild reaction conditions, broad substrate scope and good yield. Among the synthesized compounds, the following five compounds 3aa, 3bd, 3ec, 3fa, and 3fd showed anticancer activity against a human breast cancer cell line (MCF-7) and a cervical cancer cell line (HeLa).

Comparative study on heat transfer and friction drag in the flow of various hybrid nanofluids effected by aligned magnetic field and nonlinear radiation.

The key purpose of the existing article is to discuss the effects of various hybrid nanofluids and a simple nanofluid over the heat transfer and friction drags along a stretched surface. The various kinds of hybrid nanofluids and a simple nanofluid together with the effects of aligned magnetic field, nonlinear radiation and suction have been taken into consideration. These hybrid nanofluids are prepared by suspending a couple of distinct nanoparticles [Formula: see text] and [Formula: see text] into the base fluids [Formula: see text] and [Formula: see text]. The comparison of various graphical results of skin friction coefficient, rate of heat transfer, velocity and temperature for two different hybrid nanofluids [Formula: see text]/[Formula: see text], [Formula: see text]/[Formula: see text] and a simple nanofluid [Formula: see text]/[Formula: see text] is considered. Moreover, the impact of surface stretching, aligned magnetic field and thermal radiation over the velocity, temperature, skin friction coefficient and local Nusselt number are also considered. The outcomes drawn from this modern research is that the hybrid nanofluid [Formula: see text]/[Formula: see text] is quite effective in cooling and heating in comparison to the other hybrid nanofluids [Formula: see text]/[Formula: see text], [Formula: see text]/[Formula: see text] and a simple nanofluid [Formula: see text]. Based on these findings we could say that the suspension of multiple particles in the composition of two or more base fluids provides a better rate of heat transfer and limits the friction drag.

Frequency of Intraoperative Hypotension After the Induction of Anesthesia in Hypertensive Patients with Preoperative Angiotensin-converting Enzyme Inhibitors.

Introduction The renin-angiotensin-aldosterone system (RAAS) is an important target in the treatment of hypertension. Angiotensin-converting enzyme (ACE) inhibitors block the conversion of angiotensin I to angiotensin II. ACE inhibitors not only treat hypertension but also decrease morbidity and mortality in heart failure patients and in patients with acute myocardial infarction. The discontinuation of ACE inhibitors before the surgery is still controversial. To assess the current magnitude of the problem in our population, we aimed to conduct this study, which evaluated the frequency of intraoperative hypotension after the induction of anesthesia in controlled hypertensive patients with preoperative ACE inhibitors. Material and methods This descriptive case series study was conducted at a tertiary hospital in a developing country after approval from the Ethics Review Committee. A total of 115 adult patients, from 16 to 60 years of age, who have undergone elective surgery, have controlled hypertension on the desired drugs for at least six months, have no history of any cardiac event, and have taken the drug on the morning of the surgery, were included in the study after written consent. The demographic data of the patients were entered into the proforma. Preoperative systolic, diastolic, and mean arterial pressure were recorded by the researcher or an assignee in the preoperative holding area. The patients were followed in the recovery room by the team conducting the study until 10 minutes after the arrival of the patient in the recovery room. All statistical analyses were performed using Statistical Packages for the Social Sciences version 19 (SPSS Inc., Chicago, IL). p-value ≤0.05 was considered significant. Results Of the 115 patients, 56 (48.7%) patients were in the age group between 51 and 60 years of age; 38 patients were between the ages of 41 and 50 years and only 21 patients were 40 years or less. On gender, 68 patients were female and 47 were male. According to body mass index (BMI), the majority of the patients were in the overweight group, amounting to 53 (46%), and 86 (74.78%) patients were known diabetics. Overall, 77 (66.96%) of the patients developed intraoperative hypotension with 41 (35.65%) patients requiring the use of vasopressors in order to correct the hypotension. No statistically significant difference was found between demographic and clinical variables. Conclusion Intraoperative hypotension is more frequent in patients with controlled hypertension on ACE inhibitors although more studies need to be conducted on a larger population in order to determine a more definitive result.

A sensitive TICT Probe exhibiting ratiometric fluorescence repose to detect hydrazine in solution and gas phase.

A twisted intramolecular charge transfer (TICT) based probe, dicyanovinyl-9-phenylanthracene (DPA) has been designed and synthesized for the detection of hydrazine (N2H4) with good limit of detection (LOD, 7.85 nM (0.25 ppb)). Upon interaction with hydrazine the terminal electron withdrawing dicyanovinyl function is changed to electron donating amino/hydrazone function. Consequently, the significant change in the photophysical property of the probe is attributed to a change in orientation of charge propagation. The probe with hydrazine shows ratiometric fluorescence "turn-on" response as well as naked-eye sensitive color change in the medium. The surface morphology studies (SEM and TEM) suggested about amorphousness and crystalline nature of the probe DPA and derivative DPA-HDz, respectively. The conducting behavior of the probe decreases upon interaction with hydrazine because of decrease in amorphousness of the matrix and increase in relatively more rigid crystalline structure. Additionally, the probe been utilized to detect hydrazine vapor in solution and on test paper strip with good naked-eye sensitive responses.

DCS: Distributed Caching Strategy at the Edge of Vehicular Sensor Networks in Information-Centric Networking.

Information dissemination in current Vehicular Sensor Networks (VSN) depends on the physical location in which similar data is transmitted multiple times across the network. This data replication has led to several problems, among which resource consumption (memory), stretch, and communication latency due to the lake of data availability are the most crucial. Information-Centric Networking (ICN) provides an enhanced version of the internet that is capable of resolving such issues efficiently. ICN is the new internet paradigm that supports innovative communication systems with location-independent data dissemination. The emergence of ICN with VSNs can handle the massive amount of data generated from heterogeneous mobile sensors in surrounding smart environments. The ICN paradigm offers an in-network cache, which is the most effective means to reduce the number of complications of the receiver-driven content retrieval process. However, due to the non-linearity of the Quality-of-Experience (QoE) in VSN systems, efficient content management within the context of ICN is needed. For this purpose, this paper implements a new distributed caching strategy (DCS) at the edge of the network in VSN environments to reduce the number of overall data dissemination problems. The proposed DCS mechanism is studied comparatively against existing caching strategies to check its performance in terms of memory consumption, path stretch ratio, cache hit ratio, and content eviction ratio. Extensive simulation results have shown that the proposed strategy outperforms these benchmark caching strategies.

Monoallelic expression in melanoma.

BACKGROUND: Monoallelic expression (MAE) is a frequent genomic phenomenon in normal tissues, however its role in cancer is yet to be fully understood. MAE is defined as the expression of a gene that is restricted to one allele in the presence of a diploid heterozygous genome. Constitutive MAE occurs for imprinted genes, odorant receptors and random X inactivation. Several studies in normal tissues have showed MAE in approximately 5-20% of the cases. However, little information exists on the MAE rate in cancer. In this study we assessed the presence and rate of MAE in melanoma. The genetic basis of melanoma has been studied in depth over the past decades, leading to the identification of mutations/genetic alterations responsible for melanoma development. METHODS: To examine the role of MAE in melanoma we used 15 melanoma cell lines and compared their RNA-seq data with genotyping data obtained by the parental TIL (tumor infiltrating lymphocytes). Genotyping was performed using the Illumina HumanOmni1 beadchip. The RNA-seq library preparation and sequencing was performed using the Illumina TruSeq Stranded Total RNA Human Kit and subsequently sequenced using a HiSeq 2500 according to manufacturer's guidelines. By comparing genotyping data with RNA-seq data, we identified SNPs in which DNA genotypes were heterozygous and corresponding RNA genotypes were homozygous. All homozygous DNA genotypes were removed prior to the analysis. To confirm the validity to detect MAE, we examined heterozygous DNA genotypes from X chromosome of female samples as well as for imprinted and olfactory receptor genes and confirmed MAE. RESULTS: MAE was detected in all 15 cell lines although to a different rate. When looking at the B-allele frequencies we found a preferential pattern of complete monoallelic expression rather then differential monoallelic expression across the 15 melanoma cell lines. As some samples showed high differences in the homozygous and heterozygous call rate, we looked at the single chromosomes and showed that MAE may be explained by underlying large copy number imbalances in some instances. Interestingly these regions included genes known to play a role in melanoma initiation and progression. Nevertheless, some chromosome regions showed MAE without CN imbalances suggesting that additional mechanisms (including epigenetic silencing) may explain MAE in melanoma. CONCLUSION: The biological implications of MAE are yet to be realized. Nevertheless, our findings suggest that MAE is a common phenomenon in melanoma cell lines. Further analyses are currently being undertaken to evaluate whether MAE is gene/pathway specific and to understand whether MAE can be employed by cancers to achieve a more aggressive phenotype.

Potentially Modifiable Risk Factors for Long-Term Cognitive Impairment After Critical Illness: A Systematic Review.

Long-term cognitive impairment is common in survivors of critical illness. Little is known about the etiology of this serious complication. We sought to summarize current scientific knowledge about potentially modifiable risk factors during intensive care unit (ICU) treatment that may play a substantial role in the development of long-term cognitive impairment. All searches were run on October 1, 2017. The search strategy included Ovid MEDLINE, Ovid Embase, Ovid CDR, Cochrane Central Register of Controlled Trials and Database of Abstracts of Reviews of Effect, Scopus, and Web of Science, and included MeSH headings and keywords related to intensive care, critical care, and cognitive disorders. Searches were restricted to adult subjects. Inclusion required follow-up cognitive evaluation at least 2 months after ICU discharge. Studies assessing patients with cardiac arrest, traumatic brain injury, and cardiac surgery history were excluded. The search strategy resulted in 3180 studies. Of these, 28 studies (.88%) met our inclusion criteria and were analyzed. Delirium and duration of delirium were associated with long-term cognitive impairment after ICU admission in 6 of 9 studies in which this factor was analyzed. Weaker and more inconsistent associations have been reported with hypoglycemia, hyperglycemia, fluctuations in serum glucose levels, and in-hospital acute stress symptoms. Instead, most of the studies did not find significant associations between long-term cognitive impairment and mechanical ventilation; use of sedatives, vasopressors, or analgesic medications; enteral feeding; hypoxia; extracorporeal membrane oxygenation; systolic blood pressure; pulse rate; or length of ICU stay. Prolonged delirium may be a risk factor for long-term cognitive impairment after critical illness, though this association has not been entirely consistent across studies. Other potentially preventable factors have not been shown to have strong or consistent associations with long-term cognitive dysfunction in survivors of critical illness.

Diagnosis implications of the whole genome sequencing in a large Lebanese family with hyaline fibromatosis syndrome.

BACKGROUND: Hyaline fibromatosis syndrome (HFS) is a recently introduced alternative term for two disorders that were previously known as juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH). These two variants are secondary to mutations in the anthrax toxin receptor 2 gene (ANTXR2) located on chromosome 4q21. The main clinical features of both entities include papular and/or nodular skin lesions, gingival hyperplasia, joint contractures and osteolytic bone lesions that appear in the first few years of life, and the syndrome typically progresses with the appearance of new lesions. METHODS: We describe five Lebanese patients from one family, aged between 28 and 58 years, and presenting with nodular and papular skin lesions, gingival hyperplasia, joint contractures and bone lesions. Because of the particular clinical features and the absence of a clinical diagnosis, Whole Genome Sequencing (WGS) was carried out on DNA samples from the proband and his parents. RESULTS: A mutation in ANTXR2 (p. Gly116Val) that yielded a diagnosis of HFS was noted. CONCLUSIONS: The main goal of this paper is to add to the knowledge related to the clinical and radiographic aspects of HFS in adulthood and to show the importance of Next-Generation Sequencing (NGS) techniques in resolving such puzzling cases.

Methanolic bark extract of Acacia catechu ameliorates benzo(a)pyrene induced lung toxicity by abrogation of oxidative stress, inflammation, and apoptosis in mice.

Benzo(a)pyrene [B(a)P] is a well-known carcinogen present in the environment. In this study, we evaluated the protective potential of methanolic bark extract of Acacia catechu Willd. (MEBA) against the lung toxicity induced by B(a)P in Swiss albino mice. To determine the protective efficacy of MEBA, it was orally administered to the mice at two doses (200 and 400 mg/kg body weight) once daily for 7 days. Mice were also exposed (orally) to B(a)P at a dose of 125 mg/kg body weight on 7th day. Administration of B(a)P increased the activities of toxicity markers such as LDH, LPO, and XO with a subsequent decrease in the activities of tissue anti-oxidant armory (CAT, SOD, GST, GPx, GR, QR, and GSH). It also caused activation of the apoptotic and inflammatory pathway by upregulation of TNF-α, NF-kB, COX-2, p53, bax, caspase-3, and downregulating Bcl-2. Pretreatment with MEBA at two different doses (200 and 400 mg/kg body weight) significantly ameliorates B(a)P-induced increased toxicity markers and activities of detoxifying enzymes along with the levels of glutathione content. It also significantly attenuated expression of apoptotic and inflammatory markers in the lungs. Histological results further confirmed the protective role of MEBA against B(a)P-induced lung toxicity. The results indicate that MEBA may be beneficial in ameliorating the B(a)P-induced oxidative stress, inflammation, and apoptosis in the lungs of mice. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1566-1577, 2017.

Methyl jasmonate effectively enhanced some defense enzymes activity and Total Antioxidant content in harvested "Sabrosa" strawberry fruit.

The use of chemicals in postharvest technology of horticultural crops is highly restricted and it is necessary to introduce safe food preserving methods. Strawberry is very susceptible to postharvest losses and more than 50% of harvested fruit is lost in Iran. Effect of postharvest treatment with methyl jasmonate (at 0, 8, and 16 µmol L(-1)) on some quality attributes of Sabrosa strawberry fruit during storage at 1 ± 0.5°C with 90-95% RH for 14 days followed by 24 h at 20°C was studied. Methyl jasmonate, at both concentrations, decreased weight loss and retained marketability of fruits. Catalase activity of treated fruits was decreased during the first days, but showed a substantial increase during the second week. Methyl jasmonate, in a concentration-dependent manner, enhanced peroxidase activity. Fruit total antioxidant capacity was enhanced by methyl jasmonate treatment. The results indicated that methyl jasmonate plays a key role in establishing resistance against stresses, enhancing fruit defense systems, antioxidant capacity, and storage life leading to decreased postharvest losses. This phytochemical has a good potential to be used in postharvest technology of Sabrosa strawberry fruit and enhance the fruit postharvest life.

Temple-Baraitser Syndrome and Zimmermann-Laband Syndrome: one clinical entity?

BACKGROUND: KCNH1 encodes a voltage-gated potassium channel that is predominantly expressed in the central nervous system. Mutations in this gene were recently found to be responsible for Temple-Baraitser Syndrome (TMBTS) and Zimmermann-Laband syndrome (ZLS). METHODS: Here, we report a new case of TMBTS diagnosed in a Lebanese child. Whole genome sequencing was carried out on DNA samples of the proband and his parents to identify mutations associated with this disease. Sanger sequencing was performed to confirm the presence of detected variants. RESULTS: Whole genome sequencing revealed three missense mutations in TMBTS patient: c.1042G > A in KCNH1, c.2131 T > C in STK36, and c.726C > A in ZNF517. According to all predictors, mutation in KCNH1 is damaging de novo mutation that results in substitution of Glycine by Arginine, i.e., p.(Gly348Arg). This mutation was already reported in a patient with ZLS that could affect the connecting loop between helices S4-S5 of KCNH1 with a gain of function effect. CONCLUSIONS: Our findings demonstrate that KCNH1 mutations cause TMBTS and expand the mutational spectrum of KCNH1 in TMBTS. In addition, all cases of TMBTS were reviewed and compared to ZLS. We suggest that the two syndromes are a continuum and that the variability in the phenotypes is the result of the involvement of genetic modifiers.