Intraoperative Diagnosis of Gallbladder Volvulus.

Background: A gallbladder torsion typically presents as an acute abdomen presentation with nonspecific clinical signs. When not detected by a clinician preoperatively, it can lead to the delay of emergency surgery and possible misdiagnosis for other, more common causes of an acute abdomen. Case Presentation. We report the case of acute gallbladder volvulus in an 80-year-old woman complaining of constant pain in the right upper quadrant of the abdomen. Conclusions: The patient was successfully treated with cholecystectomy. The case highlights the high index of suspicion required to diagnose the condition preoperatively in this population of patients to reduce complications such as biliary peritonitis and death.

Frequency and mutational spectrum of PIK3CA gene mutations in breast cancer patients: Largest and first report from Lebanon.

The PIK3CA pathway is one of the most frequently altered pathways in human cancers, especially in breast cancer with approximately 40% of HR+/HER2- advanced breast cancer cases exhibiting mutations in the PIK3CA gene. While the mutations can occur across the entire gene, the most common are observed in exon 9 corresponding to the helical domain, and in exon 20 encompassing the kinase domain. This study constitutes the first attempt at determining the frequency and mutational spectrum in Lebanese breast cancer patients. For this purpose, DNA samples from 280 breast cancer patients from across Lebanon were screened for PIK3CA mutations using the Therascreen® PIK3CA RGQ Real-time PCR assay. In line with previous reports, 38.57% of cases were positive for at least one PIK3CA mutation, among which approximately 59% were in exon 9 and 37% in exon 20. However, PIK3CA mutations are breast cancer are heterogeneous whereby 20% of known PIK3CA mutants might not be detected by compact PCR based assays. Thus, the adoption of comprehensive Next Generation Sequencing based panels to decipher the complete clinical, molecular and immunohistochemical profile of breast cancer tumor requires further investigation.

Extension of the Trotterized Unitary Coupled Cluster to Triple Excitations.

The Trotterized Unitary Coupled Cluster Single and Double (UCCSD) ansatz has recently attracted interest due to its use in Variation Quantum Eigensolver (VQE) molecular simulations on quantum computers. However, when the size of molecules increases, UCCSD becomes less interesting as it cannot achieve sufficient accuracy. Including higher-order excitations is therefore mandatory to recover the UCC's missing correlation effects. Here, we extend the Trotterized UCC approach via the addition of (true) Triple T excitations introducing UCCSDT. We also include both spin and orbital symmetries. Indeed, in practice, the latter help to reduce unnecessary circuit excitations and thus accelerate the optimization process enabling researchers to tackle larger molecules. Our initial numerical tests (12-14 qubits) show that UCCSDT improves the overall accuracy by at least two orders of magnitude with respect to standard UCCSD. Overall, the UCCSDT ansatz is shown to reach chemical accuracy and to be competitive with the CCSD(T) gold-standard classical method of quantum chemistry.

Synthesis, molecular docking, and pharmacological evaluation of 5-(4-(2-(5-ethyl pyridine-2-yl) ethoxy) benzyl)-3-(phenylsulfonyl) thiazolidine-2, 4-dione against HFD-induced diabesity via interaction with the CB1 receptor.

Objectives: CB1 antagonism arbitrates a dormant shape to the endocannabinoid system that alleviates diverse pathological incidents of diabesity. The present study pursued the synthesis and evaluation of thiazolidine derivative (BAC) having pleiotropic action on CB1R, with or without AM251 (selective antagonist of the CB1 receptor) against high-fat diet (HFD) induced diabesity in C57BL/6 mice. Materials and Methods: A molecular docking study for CB1 antagonistic potential was conducted by Maestro 11.4 program (Schrodinger Inc., USA), and the thiazolidine derivative BAC was synthesized. The assessment of varied parameters including anthropometric, neurobehavioral, hyperglycemia, dyslipidemia, oxidative stress, and inflammatory cytokines was evaluated in HFD-fed animals as compared with individual and combined treatments of BAC and AM251. Results: Incomparable to AM251, the treatment of BAC was reported for a significant reduction in food intake and obesity, diabetic biomarkers, lipid profile, oxidative stress, and proinflammatory cytokine release. Moreover, the BAC treatment showed no significant alteration in neurobehavioral activity, including anxiety and depression. Conclusion: The preliminary in silico study suggests that BAC has a close interaction with CB1 antagonism but has no sign of neurobehavioral alteration. Simultaneously, this compound showed significant ability to ameliorate diversity by the underlying mechanisms of minimizing oxidative stress, regularizing the lipid profile, and reducing pro-inflammatory cytokines.

Minocycline Hydrochloride Controlled-release Microsphere Preparation Process Optimization Based on the Robust Design Method.

OBJECTIVES: The objective of the present study is to establish a robust preparation method that could steadily produce minocycline hydrochloride (MCH) microspheres regardless of used polymer types. MATERIALS AND METHODS: Taguchi's Robust Experimental Design methodology was employed to optimize the process parameters for MCH-loaded poly(D,L-lactide-co-glycolide) (PLGA) microspheres. In the experimental design, seven controllable factors, i.e., preparation method, pH of the aqueous phase, volume of the aqueous phase, volume of dichloromethane, rotation speed, temperature, and amount of polyvinyl alcohol, were considered for the optimization of process parameters. PLGA types with different lactide/glycolide ratios were considered the uncontrollable (noise) factor. Based on the L18 orthogonal array, 18 experimental runs were conducted for each type of PLGA. The encapsulation efficiency (EE) and in vitro release rate were evaluated for all the prepared formulations. RESULTS: Regardless of the PLGA type with different lactic/glycolic acid ratios, microspheres prepared via the solid-in-oil-in-water (S/O/W) method, showed a much higher EE and faster drug release than the microspheres prepared via the co-solvent method. Preparation methods, pH of the aqueous phase, and volume of the aqueous phase were the most influencing parameters on the EE. The confirmation experiment results indicated that the signal-to-noise ratio increased by 5.76 db from that of an initial condition. The release of minocycline was fastest with the PLGA (50:50) microspheres, followed by PLGA (75:25) and PLGA (85:15). CONCLUSION: Although the interaction between the selected factors in the evaluation was ignored, the orthogonal array design of the experiment based on Taguchi's robust experimental design methodology was sufficient to optimize the process parameters for the PLGA microspheres of MCH. The S/O/W was the main factor affecting the EE. Microspheres prepared via the S/O/W method exhibited a higher EE and faster drug release than the microspheres prepared via co-solvent method. The pH and volume of the aqueous phase were also effective parameters on the EE. A robust experimental design has been successfully applied to the optimization of the process parameters for microsphere preparation.

Difficulties in achieving a sustainable blood supply: report from the first national seminar on blood donation in Lebanon.

BACKGROUND: Lebanon has a decentralized/fragmented transfusion system. The current blood supply does not meet the World Health Organization target of achieving 100% voluntary non-remunerated blood donation (VNRD). There are currently 3 types of donors/donations in Lebanon: replacement/family donations (70-75%), VNRD (20-25%), and compensated donations (5-10%). Remunerated donations are illegal. AIMS: This report summarizes the content of presentations given during the first World Blood Donor Day seminar in Lebanon in June 2017. The aim is to describe the current Lebanese blood supply system and the major road blocks and to suggest practical recommendations that may assist in achieving 100% VNRD. METHODS: The content of presentations given during the first World Blood Donor Day seminar in Lebanon in June 2017 were summarized. RESULTS: The seminar was attended by all major stakeholders involved in transfusion medicine (Lebanese National Committee of Blood Transfusion, Hospital Blood Banks directors, Lebanese Army Blood Bank, Lebanese Red Cross and Donner Sang Compter). CONCLUSIONS: The Ministry of Public Health should focus on performing regular audits regarding the implementation of national guidelines. There is a need for a national blood supply committee, unifying all stakeholders in the transfusion and donation fields. Transfusion medicine should be declared by law as a public health issue and considered a priority for patient safety.

Composite nanofibers incorporating alpha lipoic acid and atorvastatin provide neuroprotection after peripheral nerve injury in rats.

Despite the new treatment strategies within the last 30 years, peripheral nerve injury (PNI) is still a worldwide clinical problem. The incidence rate of PNIs is 1 in 1000 individuals per year. In this study, we designed a composite nanoplatform for dual therapy in peripheral nerve injury and investigated the in-vivo efficacy in rat sciatic nerve crush injury model. Alpha-lipoic acid (ALA) was loaded into poly lactic-co-glycolic acid (PLGA) electrospun nanofibers which would release the drug in a faster manner and atorvastatin (ATR) loaded chitosan (CH) nanoparticles were embedded into PLGA nanofibers to provide sustained release. Sciatic nerve crush was generated via Yasargil aneurism clip with a holding force of 50 g/cm2. Nanofiber formulations were administered to the injured nerve immediately after trauma. Functional recovery of operated rat hind limb was evaluated using the sciatic functional index (SFI), extensor postural thrust (EPT), withdrawal reflex latency (WRL) and Basso, Beattie, and Bresnahan (BBB) test up to one month in the post-operative period at different time intervals. In addition to functional recovery assessments, ultrastructural and biochemical analyses were carried out on regenerated nerve fibers. L-929 mouse fibroblast cell line and B35 neuroblastoma cell line were used to investigate the cytotoxicity of nanofibers before in-vivo experiments. The neuroprotection potential of these novel nanocomposite fiber formulations has been demonstrated after local implantation of composite nanofiber sheets incorporating ALA and ATR, which contributed to the recovery of the motor and sensory function and nerve regeneration in a rat sciatic nerve crush injury model.

Management of patients with high-risk and advanced prostate cancer in the Middle East: resource-stratified consensus recommendations.

PURPOSE: Prostate cancer care in the Middle East is highly variable and access to specialist multidisciplinary management is limited. Academic tertiary referral centers offer cutting-edge diagnosis and treatment; however, in many parts of the region, patients are managed by non-specialists with limited resources. Due to many factors including lack of awareness and lack of prostate-specific antigen (PSA) screening, a high percentage of men present with locally advanced and metastatic prostate cancer at diagnosis. The aim of these recommendations is to assist clinicians in managing patients with different levels of access to diagnostic and treatment modalities. METHODS: The first Advanced Prostate Cancer Consensus Conference (APCCC) satellite meeting for the Middle East was held in Beirut, Lebanon, November 2017. During this meeting a consortium of urologists, medical oncologists, radiation oncologist and imaging specialists practicing in Lebanon, Syria, Iraq, Kuwait and Saudi Arabia voted on a selection of consensus questions. An additional workshop to formulate resource-stratified consensus recommendations was held in March 2019. RESULTS: Variations in practice based on available resources have been proposed to form resource-stratified recommendations for imaging at diagnosis, initial management of localized prostate cancer requiring therapy, treatment of castration-sensitive/naïve advanced prostate cancer and treatment of castration-resistant prostate cancer. CONCLUSION: This is the first regional consensus on prostate cancer management from the Middle East. The following recommendations will be useful to urologists and oncologists practicing in all areas with limited access to specialist multi-disciplinary teams, diagnostic modalities and treatment resources.

A single layer spin-orbit torque nano-oscillator.

Spin torque and spin Hall effect nano-oscillators generate high intensity spin wave auto-oscillations on the nanoscale enabling novel microwave applications in spintronics, magnonics, and neuromorphic computing. For their operation, these devices require externally generated spin currents either from an additional ferromagnetic layer or a material with a high spin Hall angle. Here we demonstrate highly coherent field and current tunable microwave signals from nano-constrictions in single 15-20 nm thick permalloy layers with oxide interfaces. Using a combination of spin torque ferromagnetic resonance measurements, scanning micro-Brillouin light scattering microscopy, and micromagnetic simulations, we identify the auto-oscillations as emanating from a localized edge mode of the nano-constriction driven by spin-orbit torques. Our results pave the way for greatly simplified designs of auto-oscillating nano-magnetic systems only requiring single ferromagnetic layers with oxide interfaces.

Simultaneous wavelength and orbital angular momentum demultiplexing using tunable MEMS-based Fabry-Perot filter.

In this paper, we experimentally demonstrate simultaneous wavelength and orbital angular momentum (OAM) multiplexing/demultiplexing of 10 Gbit/s data streams using a new on-chip micro-component-tunable MEMS-based Fabry-Perot filter integrated with a spiral phase plate. In the experiment, two wavelengths, each of them carrying two channels with zero and nonzero OAMs, form four independent information channels. In case of spacing between wavelength channels of 0.8 nm and intensity modulation, power penalties relative to the transmission of one channel do not exceed 1.45, 0.79 and 0.46 dB at the hard-decision forward-error correction (HD-FEC) bit-error-rate (BER) limit 3.8 × 10-3 when multiplexing a Gaussian beam and OAM beams of azimuthal orders 1, 2 and 3 respectively. In case of phase modulation, power penalties do not exceed 1.77, 0.54 and 0.79 dB respectively. At the 0.4 nm wavelength grid, maximum power penalties at the HD-FEC BER threshold relative to the 0.8 nm wavelength spacing read 0.83, 0.84 and 1.15 dB when multiplexing a Gaussian beam and OAM beams of 1st, 2nd and 3rd orders respectively. The novelty and impact of the proposed filter design is in providing practical, integrable, cheap, and reliable transformation of OAM states simultaneously with the selection of a particular wavelength in wavelength division multiplexing (WDM). The proposed on-chip device can be useful in future high-capacity optical communications with spatial- and wavelength-division multiplexing, especially for short-range communication links and optical interconnects.

Nanofibers: New Insights for Drug Delivery and Tissue Engineering.

Nanofibers became one of the major research areas for drug delivery and tissue engineering applications in the last decade. Depending on the simplicity of the preparation method and high drug loading capacity, nanofibers provide many advantages for therapeutic perspectives. In addition, combined systems such as embedding nanoparticles into the nanofiber structures provide a second option for delivery of dual active ingredients in the same formulation. The release rate of the active ingredients can also be modified easily by the formulation parameters depending on the desired release time for treatment. Nanofibers systems are used for the delivery of antibiotics, anticancer drugs, analgesics, hemostatic agents and various proteins for tissue engineering purposes. In addition, various applications such as medical device coating also provide new insights for the clinical use of nanofibers. The most commonly used technique for preparation of nanofibers is the electrospinning, which provides feasibility background for scale up process from laboratory to the industrial applications. The main boundary for nanofibers is the limitations for systemic route. Nanofibers are mainly designed for the delivery of active ingredients for local purposes. Regardless of the therapeutic aim, nanofibers are also perfect 3 dimensional structures that are suitable for tissue regeneration. They provide matrix structure for cell regeneration especially in applications for wound healing. This review is mainly focused on the recent advances on the preparation of nanofibers, applications for drug delivery, tissue engineering and wound healing purposes.

Far-field, linewidth and thermal characteristics of a high-speed 1550-nm MEMS tunable VCSEL.

We report an electrically pumped 1550 nm MEMS tunable VCSEL with a continuous tuning of 101 nm at 22 °C. The top MEMS-DBR with built-in stress gradient within the dielectric layers is deposited in a low-temperature PECVD chamber on an InP-based half-VCSEL, structured by surface-micromachining and electrothermally actuated for continuous wavelength tuning. With 2.6 mA threshold current, the laser shows maximum CW output power of 3.2 mW at 1560 nm. The MEMS-VCSEL operates in single-mode with SMSR > 39 dB across the entire tuning range. At 36 °C, the tuning range reaches up to 107 nm. The divergence angle of the MEMS-VCSEL is approximately 5.6° for all tuning wavelengths. The intrinsic linewidth of an unpackaged device is 21 MHz. Quasi-error-free operation at 12.5 Gbps using a directly modulated MEMS-VCSEL is reported for a record 60 nm tuning, showing the potential of the so-called colorless source in WDM applications.

Widely tunable telecom MEMS-VCSEL for terahertz photomixing.

We report frequency-tunable terahertz (THz) generation with a photomixer driven by an ultra-broadband tunable micro-electro-mechanical system vertical-cavity surface-emitting laser (MEMS-VCSEL) and a fixed-wavelength VCSEL, as well as a tunable MEMS-VCSEL mixed with a distributed feedback (DFB) diode. A total frequency span of 3.4 THz is covered in direct detection mode and 3.23 THz in the homodyne mode. The tuning range is solely limited by the dynamic range of the photomixers and the Schottky diode/photoconductor used in the experiment.

A nationwide non-interventional epidemiological data registry on myelodysplastic syndromes in Lebanon.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders characterized by peripheral blood cytopenias, blood cells dysplasia, and increased risk for progression to acute leukemia.Physicians should be vigilant in diagnosing MDS and should be aware of the contemporary therapies that are always in progress. Most of the data on MDS epidemiology and management comes from developed countries. The incidence and features of MDS in the Arab countries, among them Lebanon, are not known. We undertook a nationwide epidemiological registry study of all newly diagnosed MDS cases through 2010-2011. Patients were referred by 21 hematologists/oncologists practicing in 17 hospitals and medical centers distributed across the entire country. 58 patients (29 males and 29 females) with confirmed MDS were included. The calculated incidence rate of MDS was 0.71 per 100,000 people. The median age at diagnosis was 73 years (range 16-86). The most common complaints on presentation were fatigue (70.7%), weakness (60.3%) and pallor (43.1%). Most patients were diagnosed as refractory anemia with excess blasts (RAEB; 36.2%) and refractory cytopenia with multilineage dysplasia (RCMD; 32.8%). This paper constitutes the first epidemiological report on the incidence and specific subtypes of MDS in Lebanon.

Frequent deletions at 12q14.3 chromosomal locus in adult acute lymphoblastic leukemia.

Cytogenetic abnormalities at the 12q12-q14 chromosomal locus are rarely detected in acute lymphoblastic leukemia (ALL). To examine submicroscopic deletions at this locus, we analyzed 78 adult precursor B- and T-cell ALL cases [27 with Philadelphia chromosome (Ph)-negative B-cell ALL, 20 with Ph-negative B-cell ALL with expression of one or two myeloid markers, 18 with Ph-positive B-cell ALL, and 13 with T-cell ALL] using a panel of 13 microsatellite (MST) markers that span the 12q12-q14.3 region. The status of MST markers was evaluated by use of polymerase chain reaction performed with fluorescence-labeled primers and automated fragment analysis. The MST marker analyses showed submicroscopic deletions at the 12q14.3 locus in 20 of the 78 ALL cases (26%). The frequency of deletions was highest in Ph-negative B-cell ALL (13 of 27, 48%) compared with that in Ph-negative B-cell ALL with expression of myeloid markers (4 of 20, 20%), Ph-positive B-cell ALL (2 of 18, 11%), and T-cell ALL (1 of 13, 8%). Deletion frequencies of MST markers along the 12q12-q14.3 locus suggest that the targeted gene of deletion is located within a 170-kb region bordered by the markers D12S1504 (approximately 65 kb upstream of HMGA2) and D12S1509 (in intron 3 of HMGA2) at the 12q14.3 locus. These submicroscopic deletions at the 12q14.3 locus may play a role in the pathogenesis of ALL, particularly in Ph-negative precursor B-cell ALL.