Pseudohalide Ions as Ligands to Tune Architecture and Luminescence of Polymetallic CU(I) Assemblies.

The reaction of preassembled Cu(I) bimetallic units {Cu2(dppm)2} and {Cu2(dppa)2} (dppm: bis(diphenylphosphino)methane and dppa: bis(diphenylphosphino)amine) with pseudohalide linkers (azido, dicyanamide, and tricyanomethanide) allows for the quantitative and selective preparation of three discrete tetrametallic metallacycles of formula [Cu4(µ2-dppm)4(N3)2](PF6)2, [Cu4(µ2-dppm)4(N(CN)2)2](PF6)2, and [Cu4(µ2-dppm)4(C(CN)3)4]. To explore further the impact of the linker on the architecture and dimensionality of the molecular edifice, the study was extended to more sophisticated tetradentate cyanocarbanion ligands (tcnsMe-: 2-(methylthio)-1,1,3,3-propanetetracarbonitrile and tcnsEt-: 2-(ethylthio)-1,1,3,3-propanetetracarbonitrile). Three ladder-like one-dimensional coordination polymers and an octametallic metallacycle have been obtained. The careful comparison of the metric and geometrical intramolecular and intermolecular parameters observed in this series of seven derivatives allows for rationalization of their molecular architectures. The subtle balance between the length and steric hindrance of the ligand and the formation of noncovalent interaction networks greatly influences the topology and dimensionality of the resulting assemblies and will be discussed hereafter. The photophysical properties of these seven polymetallic Cu(I) compounds have also been also studied.

Microbes-mediated synthesis strategies of metal nanoparticles and their potential role in cancer therapeutics.

Past few years have seen a paradigm shift towards ecofriendly, green and biological fabrication of metal nanoparticles (MNPs) for diverse nanomedicinal applications especially in cancer nanotheranostics. Besides, the well-known green synthesis methods of plant materials, the potential of the microbial world (bacteria, fungi, alga, etc.) in biofabrication is equally realized. Biomolecules and enzymes in the microbial cells are capable of catalyzing the biosynthesis process. These microbial derived inorganic nanoparticles have been frequently evaluated as potential agents in cancer therapies revealing exciting results. Through, cellular and molecular pathways, these microbial derived nanoparticles are capable of killing the cancer cells. Considering the recent developments in the anticancer applications of microbial derived inorganic MNPs, a dire need was felt to bring the available information to a single document. This manuscript reviews not only the mechanistic aspects of the microbial derived MNPs but also include the diverse mechanisms that governs their anticancer potential. Besides, an updated literature review is presented that includes studies of 2019-onwards.

Ophthalmic injuries from the beirut blast: Managing long-term consequences.

The 2020 Beirut Port explosion was one of the largest non-nuclear urban explosions in history, and resulted in a plethora of oculofacial injuries. In this retrospective study, we present the two year follow up ophthalmic outcomes of the survivors of the blast. Only 16 out of 39 patients continued follow up at our center, with 13 having delayed complications and 7 requiring further surgery. The most common delayed complications related to the eyelid, lacrimal system, and orbit. Treatment of disfiguring facial and peri-ocular scarring with laser-assisted drug delivery of topical 5-fluorouracil showed great promise and significantly improved patients' functional and well as cosmetic outcomes.

Impact of Intermolecular Non-Covalent Interactions in a CuI 8 PdII 1 Discrete Assembly: Conformers' Geometries and Stimuli-Sensitive Luminescence Properties.

A new highly solid-state luminescent phase of a previously reported weakly luminescent CuI 8 PdII 1 dicationic assembly is reported revealing the high geometrical versatility of this moiety that importantly alters its luminescent properties. This very minor new species Bc is based on a different conformer scaffold than the one encountered in the previously reported Bo form and, essentially differs from Bo by displaying shorter CuI -CuI intermetallic distances. DFT calculations allow concluding that the predominance in the solid-state of the weakly luminescent and less stable Bo phase is due to the extra stability induced by a larger number of intermolecular non-covalent π-CH interactions in its crystalline packing and not by the intrinsic stability of the CuI 8 PdII 1 dicationic moiety. Calculations also revealed that a more stable conformation Bcalc is expected in vacuum, which bears a different distribution of CuI -CuI intermetallic distances than the dications in Bo and Bc phases. Taking into account that the geometrical alterations are associated to drastic changes of luminescence properties, this confer to the CuI 8 PdII 1 assembly high potentiality as stimuli-sensitive luminescent materials. Indeed, by applying mechanical or thermal stress to samples of Bo phase, new phases Bg and Bm , respectively, were obtained. Alterations of the solid-state photophysical properties of these new species compared to those recorded for Bo are reported together with a combined experimental and computed study of the structures/properties relationships observed in these phases.

Borderline ovarian tumors: a retrospective cohort study on single institution experience, practice patterns and outcomes.

Borderline ovarian tumours (BOTs) commonly affect young nulliparous women, thus making fertility-preserving approaches more desirable. Women who opt for conservative management should be counselled about disease recurrence. In this retrospective study, the medical records of 57 women with BOT treated at the American University of Beirut Medical Centre between January 1986 and May 2018 were reviewed. Clinical, pathologic, and demographic data were collected and analysed to identify variables associated with poor clinical outcomes including advanced disease and risk of recurrence. Younger and nulliparous women were more likely to undergo fertility-sparing surgery. The open approach was adopted for women with larger adnexal masses and was associated with more blood loss with a mean difference of 172 mL (95% CI [110-235], p-value < .001) but no significant difference in operative time and length of hospital stay compared to the laparoscopic approach. CA-125 correlated with an advanced International Federation of Gynaecology and Obstetrics (FIGO) stage (p = .004). The recurrence rate was found to be 7% with a median recurrence time of 41.5 months.IMPACT STATEMENTWhat is already known on this subject? BOTs are common in young nulliparous women who often desire fertility-sparing procedures. Prognostic factors associated with disease severity and recurrence remain controversial.What do the results of this study add? This study presents an opportunity to understand the disease behaviour and compare local practices and outcomes to what was reported in the literature. CA-125 appears to be a useful marker in predicting the stage of BOT.What are the implications of these findings for clinical practice and/or further research? Future research should focus on exploring whether BOTs with micropapillary features represent an aggressive histologic subtype more prone to recurrence.

The accuracy and clinical impact of intraoperative frozen section in determining the extent of surgical intervention in patients with early stage endometrial cancer.

The aim of this study was to compare intraoperative frozen section (FS) with the final pathology (FP), and determine its clinical impact in clinically apparent early stage endometrial cancer (EC) at the American University of Beirut Medical Center (AUBMC). Data for patients 18 years or older, with clinically apparent early stage, grade 1 or 2, endometrioid EC, who underwent hysterectomy ± lymph node dissection (LND) at AUBMC between January 1st 1996 and June 30th 2016 were retrospectively reviewed. 70 patients were included. The overall concordance between FS and FP was 92.3% for histological subtype, 77% for tumour grade, 82% for Myometrial invasion (MI) and 100% for tumour size. At a median follow up of 30 months, 8 recurrences (11.4%) were noted, with a 5-year PFS and OS of 76 and 84% respectively, with a trend towards lower recurrence and improved survival in patients who underwent FS or LND.Impact statementWhat is already known on this subject? Hysterectomy and bilateral salpingo-oophorectomy is the standard surgery for stage I endometrial cancer (EC). Intraoperative frozen section (FS) facilitates the decision on performing lymph node dissection (LND). However, its accuracy and clinical impact have been questioned.What do the results of this study add? Our objective is to compare FS with the final pathology (FP), and determine its clinical impact in clinically apparent early stage EC at the American University of Beirut Medical Center (AUBMC). There is a lack of standardisation regarding FS use and reporting at AUBMC.What are the implications of these findings for clinical practice and/or further research? The strong correlation between FS and FP can serve as a tool to guide decision to perform LND in patients with apparent early stage disease, where use of sentinel LN biopsy technique is not available.

Microglial IL-10 and ß-endorphin expression mediates gabapentinoids antineuropathic pain.

Gabapentinoids are recommended first-line treatments for neuropathic pain. They are neuronal voltage-dependent calcium channel α2δ-1 subunit ligands and have been suggested to attenuate neuropathic pain via interaction with neuronal α2δ-1 subunit. However, the current study revealed their microglial mechanisms underlying antineuropathic pain. Intrathecal injection of gabapentin, pregabalin and mirogabalin rapidly inhibited mechanical allodynia and thermal hyperalgesia, with projected ED50 values of 30.3, 6.2 and 1.5 µg (or 176.9, 38.9 and 7.2 nmol) and Emax values of 66%, 61% and 65% MPE respectively for mechanical allodynia. Intrathecal gabapentinoids stimulated spinal mRNA and protein expression of IL-10 and ß-endorphin (but not dynorphin A) in neuropathic rats with the time point parallel to their inhibition of allodynia, which was observed in microglia but not astrocytes or neurons in spinal dorsal horns by using double immunofluorescence staining. Intrathecal gabapentin alleviated pain hypersensitivity in male/female neuropathic but not male sham rats, whereas it increased expression of spinal IL-10 and ß-endorphin in male/female neuropathic and male sham rats. Treatment with gabapentin, pregabalin and mirogabalin specifically upregulated IL-10 and ß-endorphin mRNA and protein expression in primary spinal microglial but not astrocytic or neuronal cells, with EC50 values of 41.3, 11.5 and 2.5 µM and 34.7, 13.3 and 2.8 µM respectively. Pretreatment with intrathecal microglial metabolic inhibitor minocycline, IL-10 antibody, ß-endorphin antiserum or µ-opioid receptor antagonist CTAP (but not κ- or δ-opioid receptor antagonists) suppressed spinal gabapentinoids-inhibited mechanical allodynia. Immunofluorescence staining exhibited specific α2δ-1 expression in neurons but not microglia or astrocytes in the spinal dorsal horns or cultured primary spinal cells. Thus the results illustrate that gabapentinoids alleviate neuropathic pain through stimulating expression of spinal microglial IL-10 and consequent ß-endorphin.

Silver nanoparticles biosynthesized from secondary metabolite producing marine actinobacteria and evaluation of their biomedical potential.

Biosynthesis of silver nanoparticles (AgNPs) from marine actinobacteria offers a promising avenue for exploring bacterial extracts as reducing and stabilizing agents. We report extracellular extracts of Rhodococcus rhodochrous (MOSEL-ME29) and Streptomyces sp. (MOSEL-ME28), identified by 16S rRNA gene sequencing for synthesis of AgNPs. Ultrafine silver nanoparticles were biosynthesized using the extracts of R. rhodochrous and Streptomyces sp. and their possible therapeutic applications were studied. The physicochemical properties of nanoparticles were established by HR-SEM/TEM, SAED, UV-Vis, EDS, XRD, and FTIR. UV-Vis spectra displayed characteristic absorption at 430 nm and 412 nm for AgNPs from Streptomyces sp. (S-AgNPs) and Rhodococcus sp. (R-AgNPs), respectively. HR-SEM/TEM, XRD, EDS analysis confirmed the spherical shape, crystalline nature, and elemental formation of silver. Crystallite or grain size was deduced as 5.52 nm for R-AgNPs and 35 nm for S-AgNPs. Zeta-potential indicated electrostatic negative charge for AgNPs, while FTIR revealed the presence of diverse functional groups. Disc diffusion assay indicated the broad-spectrum antibacterial potential of S-AgNPs with the maximum inhibition of B. subtilis while R-AgNPs revealed potency against P. aeruginosa at 10 µg/mL concentration. Biogenic AgNPs revealed antileishmanial activity and the IC50 was calculated as 164 µg/mL and 184 µg/mL for R-AgNPs and S-AgNPs respectively. Similarly, the R-AgNPs and S-AgNPs revealed anti-cancer potential against HepG2 and the IC50 was calculated as 49 µg/mL and 69 µg/mL for R-AgNPs and S-AgNPs, respectively. Moreover, the antioxidant activity showed significant results. MTT assay on RD cells, L20B cells, and Hep-2C indicated intensification in viability by reducing the concentration of R-AgNPs and S-AgNPs. The R-AgNPs and S-AgNPs inhibited sabin-like poliovirus (1TCID50 infection in RD cells). Furthermore, hemocompatibility at low concentrations has been confirmed. Hence, it is concluded that biogenic-AgNPs has the potential to be used in diverse biological applications and that the marine actinobacteria are an excellent resource for fabrication of AgNPs.

Quality of diabetes care in patients with schizophrenia: a case-control study in Qatar.

BACKGROUND: Patients with schizophrenia are at least twice as likely to develop diabetes mellitus compared to the general population. This is of significance in Qatar given the high prevalence of obesity and diabetes. Furthermore, the lifespan of people with schizophrenia is shortened by approximately 15 years, partly due to long-term microvascular and macrovascular complications. High quality diabetes care can significantly reduce morbidity and mortality. We assessed the level of diabetes care delivered to patients in Qatar with schizophrenia and diabetes compared to those with diabetes alone. METHODS: We performed a retrospective chart review of patients with diabetes mellitus with (n = 73) and without (n = 73) schizophrenia. Demographic information and electronic medical records were reviewed to determine adherence to American Diabetes Association standards of diabetes care in the last 6 and 12 months. Optimal diabetes care was defined as having completed glycated hemoglobin (HbA1c), lipid profile and retinal examination within 12 months. RESULTS: Optimal diabetes care was significantly lower in patients with schizophrenia and diabetes compared to diabetes alone [26.0% (n = 19/73) vs 52.1% (n = 38/73), p = 0.002]. Patients with diabetes and schizophrenia were also significantly less likely to have had body mass index recorded within 6 months (p = 0.008) and HbA1c (p = 0.006), lipid profile (p = 0.015), estimated glomerular filtration rate (eGFR) (p = 0.001) and order for retinal examination (p = 0.004) over 12 months. After adjusting for multiple comparisons, only assessment of eGFR (p = 0.01) and order for retinal examination (p = 0.04) remained significant. CONCLUSION: Patients in Qatar with schizophrenia and diabetes, receive sub-optimal diabetes care compared to those with diabetes alone.

Microglial Activation of GLP-1R Signaling in Neuropathic Pain Promotes Gene Expression Adaption Involved in Inflammatory Responses.

Background: Neuropathic pain is a common chronic pain, which is related to hypersensitivity to stimulus and greatly affects the quality of life of patients. Maladaptive gene changes and molecular signaling underlie the sensitization of nociceptive pathways. We previously found that the activation of microglial glucagon-like peptide 1 receptor (GLP-1R) could potently relieve formalin-, bone cancer-, peripheral nerve injury-, and diabetes-induced pain hypersensitivity. So far, little is known about how the gene profile changes upon the activation of GLP-1R signaling in the pathophysiology of neuropathic pain. Methods: Spinal nerve ligation (SNL) was performed to induce neuropathic pain in rats. Mechanical allodynia was assessed using von Frey filaments. The expression of IL-10, ß-endorphin, and µ-opioid receptor (MOR) was examined by real-time quantitative polymerase chain reaction (qPCR) and whole-cell recording. Measurements of cellular excitability of the substantia gelatinosa (SG) neurons by whole-cell recording were carried out. R packages of differential gene expression analysis based on the negative binomial distribution (DESeq2) and weighted correlation network analysis (WGCNA) were used to analyze differential gene expression and the correlated modules among GLP-1R clusters in neuropathic pain. Results: The GLP-1R agonist, exenatide, has an antiallodynic effect on neuropathic pain, which could be reversed by intrathecal injections of the microglial inhibitor minocycline. Furthermore, differential gene expression analysis (WGCNA) indicated that intrathecal injections of exenatide could reverse the abnormal expression of 591 genes in the spinal dorsal horn induced by nerve injury. WGCNA revealed 58 modules with a close relationship between the microglial GLP-1R pathway and features of nerve injuries, including pain, ligation, paw withdrawal latency (PWL), and anxiety. The brown module was identified as the highest correlated module, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that inflammatory responses were most correlated with PWL. To further unravel the changes of hyperalgesia-related neuronal electrophysiological activity mediated by microglia GLP-1 receptors, whole-cell recording identified that MOR agonism stimulated a robust outward current in the sham groups compared with the spinal nerve ligation (SNL) groups. This inhibitory effect on the SNL group was more sensitive than that of the sham group after bath application of ß-endorphin. Conclusions: Our results further confirmed that the GLP-1R pathway is involved in alleviating pain hypersensitivity mediated by spinal microglia activation, and inflammatory responses were the most correlated pathway associated with PWL changes in response to exenatide treatment. We found that the identification of gene regulation in response to GLP-1R activation is an effective strategy for identifying new therapeutic targets for neuropathic pain. Investigation for the activation of spinal microglial GLP-1R which might ameliorate inflammatory responses through gene expression and structural changes is providing a potential biomarker in pain management.

Intraocular Migration of Porous Polyethylene Malar Implant Used for Treacher Collins Eyelid Reconstruction.

Lower eyelid colobomas associated with Treacher Collins syndrome can be challenging to repair because of associated orbital and midfacial dysostosis. Alloplastic implants such as porous polyethylene have been advocated as readily available malar implants to help improve eyelid retraction. The authors report the first case of porous polyethylene implant insidious migration into the orbit with subsequent scleral penetration. A 14-year-old male with Treacher Collins syndrome, presented with a 3-week history of left eye pain, redness, and eyelid swelling unresponsive to topical treatment. He previously had bilateral lower lid coloboma repair with alloplastic implant placement and full-thickness skin grafts. On exam, he had left eye injection and chemosis, with left hypotropia and complete restrictive ophthalmoplegia. Imaging revealed displacement of implant into the orbit with adherence and impingement on the eye globe.

Towards the selection of embryos with the greatest implantation potential.

Choosing the most suitable embryo remains challenging as the standard approach to select top-quality embryos for transfer rely on static morphological assessment. It is completed after fertilisation, on days 3 and 5 post oocyte retrieval and evaluates the size and number of blastomeres, presence of nucleation and percentage of fragmentation for cleavage stage embryos. Because of the limited number of observations during the morphological assessment, morphokinetic development of embryos has been implemented. It shows a broader image of embryo behaviour with precise evaluation of the timing of events. Yet, studies are inconsistent and debatable in predicting the parameters to identify chromosomal abnormalities. Pre-implantation genetic testing detects dysmorphic embryos and correlate their developmental potential to the assessed morphology. However, the clinical utility of PGT-aneuploidy remains controversial. The future relies on newly described scoring systems such as artificial intelligence and non-invasive PGT, yet their application and actual success rate still lacks supportive evidence.

The spinal microglial IL-10/ß-endorphin pathway accounts for cinobufagin-induced mechanical antiallodynia in bone cancer pain following activation of α7-nicotinic acetylcholine receptors.

BACKGROUND: Cinobufagin is the major bufadienolide of Bufonis venenum (Chansu), which has been traditionally used for the treatment of chronic pain especially cancer pain. The current study aimed to evaluate its antinociceptive effects in bone cancer pain and explore the underlying mechanisms. METHODS: Rat bone cancer model was used in this study. The withdrawal threshold evoked by stimulation of the hindpaw was determined using a 2290 CE electrical von Frey hair. The ß-endorphin and IL-10 levels were measured in the spinal cord and cultured primary microglia, astrocytes, and neurons. RESULTS: Cinobufagin, given intrathecally, dose-dependently attenuated mechanical allodynia in bone cancer pain rats, with the projected Emax of 90% MPE and ED50 of 6.4 µg. Intrathecal cinobufagin also stimulated the gene and protein expression of IL-10 and ß-endorphin (but not dynorphin A) in the spinal cords of bone cancer pain rats. In addition, treatment with cinobufagin in cultured primary spinal microglia but not astrocytes or neurons stimulated the mRNA and protein expression of IL-10 and ß-endorphin, which was prevented by the pretreatment with the IL-10 antibody but not ß-endorphin antiserum. Furthermore, spinal cinobufagin-induced mechanical antiallodynia was inhibited by the pretreatment with intrathecal injection of the microglial inhibitor minocycline, IL-10 antibody, ß-endorphin antiserum and specific µ-opioid receptor antagonist CTAP. Lastly, cinobufagin- and the specific α-7 nicotinic acetylcholine receptor (α7-nAChR) agonist PHA-543613-induced microglial gene expression of IL-10/ß-endorphin and mechanical antiallodynia in bone cancer pain were blocked by the pretreatment with the specific α7-nAChR antagonist methyllycaconitine. CONCLUSIONS: Our results illustrate that cinobufagin produces mechanical antiallodynia in bone cancer pain through spinal microglial expression of IL-10 and subsequent ß-endorphin following activation of α7-nAChRs. Our results also highlight the broad significance of the recently uncovered spinal microglial IL-10/ß-endorphin pathway in antinociception.

Ethics, pandemic and environment; looking at the future of low middle income countries.

COVID-19 which started in Wuhan, China and swiftly expanded geographically worldwide, including to Low to Middle Income Countries (LMICs). This in turn raised numerous ethical concerns in preparedness, knowledge sharing, intellectual property rights, environmental health together with the serious constraints regarding readiness of health care systems in LMICs to respond to this enormous public health crisis. From the restrictions on public freedom and burgeoning socio-economic impacts to the rationing of scarce medical resources, the spread of COVID-19 is an extraordinary ethical dilemma for resource constrained nations with less developed health and research systems. In the current crisis, scientific knowledge and technology has an important role to play in effective response. Emergency preparedness is a shared responsibility of all countries with a moral obligation to support each other. This review discusses the ethical concerns regarding the national capacities and response strategies in LMICs to deal with the COVID-19 pandemic as well as the deep link between the environment and the increasing risk of pandemics.

Design, molecular modeling and anticancer evaluation of thieno[2,3-d]pyrimidine derivatives as inhibitors of topoisomerase II.

Synthesis of 4-(3,5-dimethyl-1H-pyrazol-1-yl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine 1 and its functionalized reactions as nucleophile with various electrophilic reagents were performed through facile methods to yield different cyclic and acyclic derivatives (2-17). The structures of the newly synthesized compounds were established by their elemental analysis and spectral data. Derivatives 4, 14, 16, and 17 in addition to the parent compound 1 had IC50 at ~4-10 µM against HepG2 and MCF7 and were selected for further investigations. All derivatives had high IC50 values (>60 µM) against normal fibroblasts WI38 indicating selectivity against cancer cell lines. Derivatives 4, 14, and 17 up-regulated the expression of p53 by ~3-4 folds. All derivatives caused a significant ~3-fold increase in the expression of executive caspase 3 and significant elevation in cleaved caspase 3 activity. The elevation in the expression of caspase 3 by compound 1 and derivative 16 was not accompanied by an increase in p53 expression or cleaved caspase 3 activity. These two thienopyrimidines may act directly on caspase 3. Derivative 17 was unique in reducing the expression of Topo II by ~60%. The molecular docking showed that derivatives 4 and 17 with high binding energies could bind and inhibit Topoisomerase II (Topo II). In accordance with the docking modelling, derivatives 4 and 17 reduced the Topo II concentration by 82 and 90%, respectively, compared to the untreated cells. However, the parent compound 1 also caused a significant 34% reduction in the enzyme concentration although it was not predicted as a ligand for the enzyme in the docking study. Taken together, derivatives 4, 14 and 17 showed selective cytotoxicity, could arrest cell cycle, and induce apoptosis. Furthermore, they could serve as cytostatic agents by inhibiting/reducing Topo II.

Design, efficient synthesis, docking studies, and anticancer evaluation of new quinoxalines as potential intercalative Topo II inhibitors and apoptosis inducers.

As an extension for our earlier effort in the field of discovery of anticancer agents acting on DNA and Topo II, eighteen quinoxaline derivatives were designed and synthesized. Such members were designed to possess the main essential pharmacophoric features of DNA intercalators. The cytotoxic potential of the synthesized compounds was assessed against a group of human cancer cell lines (HCT-116, HepG2, and MCF-7). Doxorubicin as potential intercalative Topo II inhibitor, was used as a positive reference. In general, compounds 12, 15, 19, 21, and 22 showed promising anti-proliferative activities against the three cell lines with IC50 values ranging from 2.81 to 10.23 µM. The cytotoxicities of the most active compounds against normal human cells (WI-38) were evaluated, and the results revealed that these compounds have low toxicity. Further examination for the most active anti-proliferative members as Topo II inhibitors was also performed, showing a narrow range of the inhibitory activities (from 0.45 to 1.06 µM). In addition, DNA/methyl green assay was carried out to evaluate DNA-binding potential of such compounds. The results indicated that these compounds have strong to moderate DNA-binding affinities ranging from 33.48 to 51.23 µM. Further studies exhibited the capability of compound 22 to induce apoptosis in HepG2 cells and can arrest growth of such cells at G2/M phase. Also, compound 22 produced a significant increase in the level of caspase- 3 (10 folds) and caspase-9 (7 folds) compared to the control cells. Molecular docking studies were also conducted to investigate possible binding interactions between the target compounds and the DNA-Topo II complex.

Effect of postoperative Trendelenburg position on shoulder pain after gynecological laparoscopic procedures: a randomized clinical trial.

BACKGROUND: Laparoscopic surgery has become a standard of care for many gynecological surgeries due to its lower morbidity, pain and cost compared to open techniques. Unfortunately, the use of carbon dioxide (CO2) to insufflate the abdomen is the main contributor to post-operative shoulder pain. METHODS: We aim to assess the effect of postoperative Trendelenburg position on shoulder pain after gynecological laparoscopic procedures. We hypothesize that maintaining the patient in Trendelenburg for 24 h postoperatively will significantly decrease postoperative shoulder pain and analgesic consumption. After obtaining written informed consent, 108 patients were prospectively randomized into two groups. In the control group, patients underwent standard gynecologic laparoscopic procedures; then after passive deflation of the pneumoperitoneum at the end of the surgery, the patients were placed in supine head up position in the post anesthesia care unit (PACU) and received our institution's common postoperative care. Patients in the intervention group were subjected to the same maneuver but were positioned in a Trendelenburg position (20 °) once fully awake and cooperative in the PACU and retained this position for the first 24 h. Numerical rating scale (NRS) was used to assess shoulder pain and nausea upon patient arrival to the PACU, at 4, 6, 12 (primary outcome) and 24 h postoperatively. Time to first rescue pain medication, total rescue pain medications and overall satisfaction with pain control were recorded. 101 patients were included in the final data analysis. RESULTS: Both groups were comparable in terms of baseline characteristics. NRS pain scores were significantly lower in the intervention group at 12 h compared to the control group (0 [0-1] versus 5 [1-4], p < 0.001), furthermore improvement in postoperative shoulder pain between time of arrival to PACU (time zero) and 12 h postoperatively was significantly higher in patients allocated to the experimental group compared to the control group. Pain scores were significantly lower in patients allocated to the experimental group versus the control group (0 [0-1] versus 5 [1-4], p < 0.001). CONCLUSION: In conclusion, Trendelenburg position is an easy non-pharmacologic intervention that is beneficial in reducing postoperative shoulder pain following gynecologic laparoscopic surgery. TRIAL REGISTRATION: Retrospectively registered at Clinicaltrials.gov, registration number NCT04129385,  date of registration: June 28, 2019.

Primary vulvar Ewing sarcoma/peripheral primitive neuroectodermal tumor with pelvic lymph nodes metastasis: A case report and review of literature.

Ewing sarcoma (ES) and peripheral primitive neuroectodermal tumors (pPNET) are soft tissue tumors that generally affect the bones. Extraosseous ES/pPNET has been rarely reported. Our patient presented with a 6 × 4 cm right subcutaneous solid vulvar lesion causing pain and discomfort. Pathology and immunohistochemistry staining showed strong positivity for CD99 and vimentin, favoring the diagnosis of ES/pPNET. Magnetic resonance imaging showed a 6-cm lesion in the right vulvar region with enlarged bilateral inguinal and right iliac lymph nodes. Fluorescence in situ hybridization test for translocation t(11;22)(q24;q12) was positive, confirming the diagnosis. The patient received three cycles of neoadjuvant chemotherapy with vincristine, adriamycin, cyclophosphamide alternating with ifosfamide and etoposide with complete response. The patient underwent vulvar radical local excision. Residual tumor measured 1.6 cm with free margins. She received four additional cycles of adjuvant chemotherapy and 30 sessions radiotherapy. She is currently disease free after 37 months. No ES/pPNET cases with pelvic lymph nodes metastasis were ever reported.

Endophyte-mediated synthesis of silver nanoparticles and their biological applications.

Biosynthesis has emerged as a frontier technology for fabrication of functionally diverse nanoparticles that possess tremendous therapeutic implications. Various biological resources have already demonstrated their potential to produce nanoparticles with interesting features. Endophytic microbes live in a symbiotic relationship with plants possessing a unique and versatile reservoir of potentially therapeutic secondary metabolites having the tendency to reduce metallic ions into nanoparticles. Successful biosynthesis of AgNPs using endophytic organisms has already been reported; however, the overall picture about its synthesis and applications is still not clear. In the current article, a comprehensive review of literature was performed for comparing different physical and biological properties of endophytic microbe-derived AgNPs. In addition, the present paper mechanistically explains the synthesis of AgNPs and their diverse pharmacognostic properties. Further studies are encouraged to understand the mechanism of biopharmaceutical effects of these endophyte-mediated NPs.

Factors associated with the public's trust in physicians in the context of the Lebanese healthcare system: a qualitative study.

BACKGROUND: The Lebanese public perceives the physician-patient relationship as flawed. The objectives of this study are to assess factors associated with the public's trust in physicians in the context of the Lebanese healthcare system and to explore potential ways to enhance it. METHODS: We conducted a qualitative study based on a grounded theory methodology using semi-structured interviews with members of the Lebanese public (not restricted to patients). We selected participants through convenience and maximum variation sampling approaches. The constant comparative analysis resulted in a theoretical framework that describes the factors influencing trust in physicians. RESULTS: Participants trusted an experienced, up-to-date, graduate of a North American or Western European school, working in a reputable hospital, with a high level of diagnostic skills. The personal characteristics that improved trust were physicians who are 'non-materialistic', have a good rapport, and have sufficient encounter time with patients. Social factors that enhance trust in the physician include: being a family member, recommended by a family member, featured in mainstream media, and/or having a good reputation. Trust increased compliance, loyalty despite occasional mistakes committed, high consultation fees, and negative attitudes towards the physician's institution. Conversely, no trust led to severed therapeutic relationship and seeking second opinions. CONCLUSION: The level of trust of members of the Lebanese public in physicians was affected by the personal characteristics of physicians, their practice or clinical skills, their interactions with the patient, finances, in addition to a number of social factors. Moreover, the level of trust had major implications on patients' interactions with their physicians.