Stunting and its association with feeding problem among under five children: a case-control study in Kuantan district, Malaysia.

INTRODUCTION: Stunting is the most prevalent form of malnutrition among infants and young children population, both globally and locally. It refers to low height-for-age children and is primarily caused by chronic under nutrition. The objective of this study is to determine the association between stunting and feeding problems and to explore the risk factors for stunting among children aged 6 to 59 months attending health clinics in the Kuantan district. MATERIALS AND METHODS: A case-control study involving 160 children that attended six health clinics in Kuantan from August to October 2021 with a ratio of 1 case: 3 controls. Data were collected from mothers using a questionnaire consisting of sociodemographic and feeding assessment adapted from a validated World Health Organization (WHO) integrated management of childhood illness (IMCI) assessment form. The data was analysed using IBM SPSS version 26.0. Binary logistic regression analysis was used to identify factors associated with stunting. The odds ratio was used to measure the strength of the association between outcome and predictor variables. The significance value was set at p<0.05. RESULTS: Children with identified feeding problems have more than four-time significantly higher risk of becoming stunted (Odds Ratios, OR: 4.2; 95% Confidence Intervals, 95%CI: 1.4, 12.8) as compared to children with no feeding problems. Specifically, children with inadequacy in feeding components; amount, variety and frequency of meal each have significantly six-time higher risk (OR: 6.2; 95%CI: 2.7, 14.5), four-time higher risk (OR: 4.2; 95%CI: 1.4, 12.3), and three-time higher risk (OR: 2.8; 95%CI: 1.1, 6.9), of becoming stunted as compared to children with adequate feeding. Additionally, with a decrease of one week in delivery week, one kilogram in birth weight and one centimetre in maternal height, there is a respectively significant 40.0% (OR: 0.6; 95%CI: 0.4, 0.9), 80.0% (OR: 0.2; 95%CI: 0.1, 0.7) and 11.0% (OR: 0.89; 95%CI: 0.82, 0.98) increase in the risk of become stunted among children. CONCLUSION: Feeding problems specifically inadequate food amount, food variety and meal frequency not following the recommendation contribute to stunting in young children. Other factors identified are lower maternal height and children with lower birth weight and delivery week. This highlights the need for more excellent detection and intervention of nutritional concerns and risk factors to prevent stunting.

Organoboron Complexes as Thermally Activated Delayed Fluorescence (TADF) Materials for Organic Light-Emitting Diodes (OLEDs): A Computational Study.

We report on organoboron complexes characterized by very small energy gaps (ΔEST) between their singlet and triplet states, which allow for highly efficient harvesting of triplet excitons into singlet states for working as thermally activated delayed fluorescence (TADF) devices. Energy gaps ranging between 0.01 and 0.06 eV with dihedral angles of ca. 90° were registered. The spin-orbit couplings between the lowest excited S1 and T1 states yielded reversed intersystem crossing rate constants (KRISC) of an average of 105 s-1. This setup accomplished radiative decay rates of ca. 106 s-1, indicating highly potent electroluminescent devices, and hence, being suitable for application as organic light-emitting diodes.

Epidemiology of elderly fractures in a tertiary hospital in Northern Ghana: a 3-year retrospective descriptive review.

PURPOSE: The incidence of elderly fractures is closely related to the increasing proportion of the elderly population in sub-Saharan Africa, making it a relevant public health concern. Epidemiological profiles of these fractures and treatment options are necessary for resource-poor settings to optimise planning and patient care. METHODS: A retrospective descriptive cross-sectional study was conducted at Tamale Teaching Hospital. Data of 69 elderly patients (60 years and above) with fractures admitted to the trauma and orthopaedic unit from January 2017 to December 2019 were collected. Simple descriptive and bivariate analysis was conducted on some variables, whereas the Chi-square was used to test for some associations for categorical data. RESULTS: The mean age of the study participants was 70.3(± 8.6). Elderly males (55.1%) were three times more likely to sustain fractures than females. The primary mechanism of injury was a road traffic accident (RTA) (59.4%), followed by falls from slips (29.0%). There was a significant association between gender and mechanisms (RTA and Falls from slips) of injury (p = 0.002). The most fractured bone was the femur (50.7%). Hip fractures (33.3%) were more common among females than males and mainly among the (71-80) age group. Open fractures were more common among males than females. CONCLUSION: RTAs were the most typical cause of fractures in the elderly. Contrary to other studies, males were more commonly involved in accidents than females, albeit females were the majority for hip fractures. Therefore, significant public health policies with resource allocation should address the unmet health needs of this unique age group in our growing populations in low- and middle-income countries.

Zn2+-Schiff's Base Complex as an "On-Off-On" Molecular Switch and a Fluorescence Probe for Cu2+ and Ag+ Ions.

The present study presents a thorough theoretical analysis of the electronic structure and conformational preference of Schiff's base ligand N,N-bis(2-hydroxybenzilidene)-2,4,6-trimethyl benzene-1,3-diamine (H2L) and its metal complexes with Zn2+, Cu2+ and Ag+ ions. This study aims to investigate the behavior of H2L and the binuclear Zn2+ complex (1) as fluorescent probes for the detection of metal ions (Zn2+, Cu2+ and Ag+) using density functional theory (DFT) and time-dependent density functional theory (TDDFT). The six conformers of the H2L ligand were optimized using the B3LYP/6-311 + + G** level of theory, while the L-2-metal complexes were optimized by applying the B3LYP functional with the LANL2DZ/6-311 + + G** mixed basis set. The gas-phase and solvated Enol-cis isomer (E-cis) was found to be the most stable species. The absorption spectra of the E-cis isomer and its metal complexes were simulated using B3LYP, CAM-B3LYP, M06-2X and ωB97X functionals with a 6-311 + + G** basis set for C, O, N and H atoms and a LANL2DZ basis set for the metal ions (Zn2+, Cu2+ and Ag+). The computational results of the B3LYP functional were in excellent agreement with the experimental results. Hence, it was adopted for performing the emission calculations. The results indicated that metal complex (1) can act as a fluorescent chemosensor for the detection of Ag+ and Cu2+ ions through the mechanism of intermolecular charge transfer (ICT) and as a molecular switch "On-Off-On" via the replacement of Cu2+ by Ag+ ions, as proved experimentally.

Computational Identification of Druggable Bioactive Compounds from Catharanthus roseus and Avicennia marina against Colorectal Cancer by Targeting Thymidylate Synthase.

Colorectal cancer (CRC) is the second most common cause of death worldwide, affecting approximately 1.9 million individuals in 2020. Therapeutics of the disease are not yet available and discovering a novel anticancer drug candidate against the disease is an urgent need. Thymidylate synthase (TS) is an important enzyme and prime precursor for DNA biosynthesis that catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) that has emerged as a novel drug target against the disease. Elevated expression of TS in proliferating cells promotes oncogenesis as well as CRC. Therefore, this study aimed to identify potential natural anticancer agents that can inhibit the activity of the TS protein, subsequently blocking the progression of colorectal cancer. Initially, molecular docking was implied on 63 natural compounds identified from Catharanthus roseus and Avicennia marina to evaluate their binding affinity to the desired protein. Subsequently, molecular dynamics (MD) simulation, ADME (Absorption, Distribution, Metabolism, and Excretion), toxicity, and quantum chemical-based DFT (density-functional theory) approaches were applied to evaluate the efficacy of the selected compounds. Molecular docking analysis initially identified four compounds (PubChem CID: 5281349, CID: 102004710, CID: 11969465, CID: 198912) that have better binding affinity to the target protein. The ADME and toxicity properties indicated good pharmacokinetics (PK) and toxicity ability of the selected compounds. Additionally, the quantum chemical calculation of the selected molecules found low chemical reactivity indicating the bioactivity of the drug candidate. The global descriptor and HOMO-LUMO energy gap values indicated a satisfactory and remarkable profile of the selected molecules. Furthermore, MD simulations of the compounds identified better binding stability of the compounds to the desired protein. To sum up, the phytoconstituents from two plants showed better anticancer activity against TS protein that can be further developed as an anti-CRC drug.

DFT Study of the Structure, Reactivity, Natural Bond Orbital and Hyperpolarizability of Thiazole Azo Dyes.

The structure, reactivity, natural bond orbital (NBO), linear and nonlinear optical (NLO) properties of three thiazole azo dyes (A, B and C) were monitored by applying B3LYP, CAM-B3LYP and ωB97XD functionals with 6-311++G** and aug-cc-pvdz basis sets. The geometrical parameters,dipolemoments,HOMO-LUMO(highest occupied molecular orbital,lowest unoccupied molecular orbital) energy gaps, absorption wavelengths and total hyperpolarizabilities were investigated in carbon tetrachloride (CCl4) chloroform (CHCl3), dichloromethane (CH2Cl2) and dimethlysulphoxide (DMSO). The donor methoxyphenyl group deviates from planarity with the thiazole azo moiety by ca. 38◦; while the acceptor dicyanovinyl, indandione and dicyanovinylindanone groups diverge by ca. 6◦. The HOMOs for the three dyes are identical. They spread over the methoxyphenyl donor moiety, the thiazole and benzene rings as π-bonding orbitals. The LUMOs are shaped up by the nature of the acceptor moieties. The LUMOs of the A, B and C dyes extend over the indandione, malononitrile and dicyanovinylindanone acceptor moieties, respectively, as π-antibonding orbitals. The HOMO-LUMO splittings showed that Dye C is much more reactive than dyes A and B. Compared to dyes A and B, Dye C yielded a longer maximum absorption wavelength because of the stabilization of its LUMOs relative to those of the other two. The three dyes show solvatochromism accompanied by significant increases in hyperpolarizability. The enhancement of the total hyperpolarizability of C compared to those of A and B is due to the cumulative action of the long π-conjugation of the indanone ring and the stronger electron-withdrawing ability of the dicyanovinyl moiety that form the dicyanovinylindanone acceptor group. These findings are facilitated by a natural bond orbital (NBO) technique. The very high total hyperpolarizabilities of the three dyes define their potent nonlinear optical (NLO) behaviour.

Fluorescence, Photophysical Behaviour and DFT Investigation of E,E-2,5-bis[2-(3-pyridyl)ethenyl]pyrazine (BPEP).

E,E-2,5-bis[2-(3-pyridyl)ethenyl]pyrazine (BPEP) has been prepared by aldol condensation between 2,5-dimethylpyrazine and pyridine-3-carboxaldehyde. It is characterized by IR, (1)H NMR, and (13)C NMR. The electronic absorption and emission properties of BPEP were studied in different solvents. BPEP displays a slight solvatochromic effect of the absorption and emission spectrum, indicating a small change in dipole moment of BPEP upon excitation. The dye solutions (1 × 10(-4) M) in CHCl3, EtOH and dioxane give laser emission in blue region upon excitation by a 337.1 nm nitrogen pulse (λ = 337 nm). The tuning range, gain coefficient (α) and emission cross - section (σe) have been determined. Ground and excited states electronic geometric optimizations were performed using density functional theory (DFT) and time-dependent density functional theory (TD-DFT), respectively. A DFT natural bond analysis complemented the ICT. The simulated maximum absorption and emission wavelengths are in line the observed ones in trend, and are proportionally red-shifted with the increase of the solvent polarity. The stability, hardness and electrophilicity of BPEP in different solvents were correlated with the polarity of the elected solvents. BPEP dye displays fluorescence quenching by colloidal silver nanoparticles (AgNPs). The fluorescence data reveal that radiative and non-radiative energy transfer play a major role in the fluorescence quenching mechanism.

Photophysical Behavior and Computational Investigation of Novel 1,4-Bis(2-(2-Phenylpyrimido[1,2-a]Benzimidazol-4-Yl)Phenoxy)Butan (BPPB) Macromolecule.

A new macromolecule pyrimido[l,2-a]benzimidazole derivative named 1,4-bis(2-(2-phenylpyrimido[1,2-a]benzimidazol-4-yl)phenoxy)butan (BPPB) has been synthesized in accepted yield using microwave assistance. The new compound BPPB has been formed by the interaction of 3,3'-((butane-1,4-diylbis(oxy))bis(2,1-phenylene))bis(1-phenylprop-2-en-1-one) (3) with 2- aminobenzimidazole (4) in the presence of potassium hydroxide as a basic catalyst in dimethylformamide (DMF) under microwave radiation for 20 min. The chemical structure of this novel compound was elucidated by elemental and spectral techniques including: FT-IR, (1)H-NMR, (13)C-NMR and mass spectra. The electronic absorption and emission spectra of BPPB were measured in different solvents. BPPB displayed a solvatochromic effect of the emission spectrum that is reflected by red shifts of its fluorescence emission maxima on increasing the solvent polarity, indicating a change of electronic charge distribution upon excitation. BPPB crystalline solids gave excimer-like emission at 535 nm with a bandwidth of ca. 60 nm. Ground and excited states electronic geometry optimizations using density functional theory (DFT) and time-dependent density functional theory (TD-DFT), respectively, complemented these spectral findings. The intramolecular charge transfer was investigated by natural bond orbital (NBO) technique.

The Thermodynamic and Kinetic Properties of 2-Hydroxypyridine/2-Pyridone Tautomerization: A Theoretical and Computational Revisit.

The gas-phase thermal tautomerization reaction between 2-hydroxypyridine (2-HPY) and 2-pyridone (2-PY) was investigated by applying 6-311++G** and aug-cc-pvdz basis sets incorporated into some density functional theory (DFT) and coupled cluster with singles and doubles (CCSD) methods. The geometrical structures, dipole moments, HOMO-LUMO energy gaps, total hyperpolarizability, kinetics and thermodynamics functions were monitored against the effects of the corrections imposed on these functionals. The small experimental energy difference between the two tautomers of 3.23 kJ/mol; was a real test of the accuracy of the applied levels of theory. M062X and CCSD methods predicted the preference of 2-HPY over 2-PY by 5-9 kJ/mol; while B3LYP functional favoured 2-PY by 1-3 kJ/mol. The CAM-B3LYP and ωB97XD functionals yielded mixed results depending on the basis set used. The source of preference of 2-HPY is the minimal steric hindrance and electrostatic repulsion that subdued the huge hyperconjugation in 2-PY. A 1,3-proton shift intramolecular gas-phase tautomerization yielded a high average activation of 137.152 kJ/mol; while the intermolecular mixed dimer interconversion gave an average barrier height of 30.844 kJ/mol. These findings are boosted by a natural bond orbital (NBO) technique. The low total hyperpolarizabilities of both tautomers mark out their poor nonlinear optical (NLO) behaviour. The enhancement of the total hyperpolarizability of 2-HPY over that of 2-PY is interpreted by the bond length alternation.

Selective Solvent-Assisted Linker Exchange (SALE) in a Series of Zeolitic Imidazolate Frameworks.

Solvent-assisted linker exchange (SALE) has recently emerged as an attractive strategy for the synthesis of metal-organic frameworks (MOFs) that are unobtainable via traditional synthetic pathways. Herein we present the first example of selective SALE in which only the benzimiadazolate-containing linkers in a series of mixed-linker zeolitic imidazolate frameworks (ZIF-69, -78, and -76) are replaced. The resultant materials (SALEM-10, SALEM-10b, and SALEM-11, respectively) are isostructural to the parent framework and in each case contain trifluoromethyl moieties. We therefore evaluated each of these materials for their hydrophobicity in condensed and gas phases. We expect that selective SALE will significantly facilitate the design of improved, and potentially complex, MOF materials with new and unusual properties.

Synthesis, Spectral Characteristics and DFT Studies of the New Dye 2,7-diacetyl-9-((dimethylamino)methylene)-9H-fluorene (DMMF) in Different Solvents.

The photophysical parameters such as electronic absorption spectra, molar absorptivity(ε), fluorescence spectra and fluorescence quantum yield (φf) of a new dye namely 2,7-diacetyl-9-((dimethylamino)methylene)-9H-fluorene (DMMF) were determined in different solvents. The electronic absorption are less sensitive to medium polarity. A bathochromic shift was observed in emission spectra(ca. 50 nm) upon increase of solvent polarity, which indicates that the singlet excited state (S1) of DMMF is more polar than the singlet ground state (So). Solid crystals of DMMF exhibit intense yellow fluorescence maximum at 550 nm with bandwidth equal 64 nm upon excitation at wavelength 365 nm. The change in dipole moment value (Δµ) was calculated by using the variation of Stokes shift with solvent polarizability (Δf) (Lippert - Mataga plot) and was found to be 7.22 and 5.5 Debye for higher and lower energy of So - S1 (π-π*) H-1 → L and So - S1 (π-π*) H → L, respectively. These results show that, the excited state is more polar than the ground state. The net photochemical quantum yields of photodecomposition of DMMF (φc) were calculated as 7.2 × 10(-5), 1.14 × 10(-4), 1.44 × 10(-4) and 2.11 × 10(-4) in different solvents such as MeOH, CH2Cl2, CHCl3 and CCl4, respectively. DFT/TD-DFT methods were used to study the geometric and electronic structures of DMMF in different solvents. A good agreement was found between the experimental and theoretical results.

Seminal plasma oxytocin and oxidative stress levels in infertile men with varicocele.

This study aimed to assess seminal plasma oxytocin (OT) and oxidative stress (OS) levels in infertile men with varicocele (Vx). A total of 131 men were divided into fertile men (n = 20), fertile men with Vx (n = 17), infertile men without Vx (n = 40) and infertile men with Vx (n = 54). OT, malondialdehyde (MDA) and glutathione peroxidase (GPx) were estimated in seminal plasma. Mean levels of seminal OT, MDA were significantly decreased, and the mean level of GPx was significantly increased in fertile men with/without Vx compared with infertile men with/without Vx. Mean levels of OT, MDA were increased, and mean level of GPx was significantly decreased in Vx grade III cases compared with Vx grades I, II cases and in bilateral Vx cases compared with unilateral Vx. There was significant negative correlation between seminal OT with sperm count, sperm motility, seminal GPx and significant positive correlation with sperm abnormal forms, seminal MDA. It is concluded that seminal OT is significantly decreased in fertile men with/without Vx compared with infertile men with/without Vx. Seminal OT demonstrated significant negative correlation with sperm count, sperm motility, seminal GPx and significant positive correlation with sperm abnormal forms, seminal MDA. Seminal OT is associated with Vx grade and its bilaterality.

Gas-Phase Thermal Tautomerization of Imidazole-Acetic Acid: Theoretical and Computational Investigations.

The gas-phase thermal tautomerization reaction between imidazole-4-acetic (I) and imidazole-5-acetic (II) acids was monitored using the traditional hybrid functional (B3LYP) and the long-range corrected functionals (CAM-B3LYP and ωB97XD) with 6-311++G** and aug-cc-pvdz basis sets. The roles of the long-range and dispersion corrections on their geometrical parameters, thermodynamic functions, kinetics, dipole moments, Highest Occupied Molecular Orbital-Lowest Unoccupied Molecular Orbital (HOMO-LUMO) energy gaps and total hyperpolarizability were investigated. All tested levels of theory predicted the preference of I over II by 0.750-0.877 kcal/mol. The origin of predilection of I is assigned to the H-bonding interaction (nN8→σ*O14-H15). This interaction stabilized I by 15.07 kcal/mol. The gas-phase interconversion between the two tautomers assumed a 1,2-proton shift mechanism, with two transition states (TS), TS1 and TS2, having energy barriers of 47.67-49.92 and 49.55-52.69 kcal/mol, respectively, and an sp³-type intermediate. A water-assisted 1,3-proton shift route brought the barrier height down to less than 20 kcal/mol in gas-phase and less than 12 kcal/mol in solution. The relatively high values of total hyperpolarizability of I compared to II were interpreted and discussed.

Towards understanding the decomposition/isomerism channels of stratospheric bromine species: ab initio and quantum topology study.

The present study aims at a fundamental understanding of bonding characteristics of the C-Br and O-Br bonds. The target molecular systems are the isomeric CH3OBr/BrCH2OH system and their decomposition products. Calculations of geometries and frequencies at different density functional theory (DFT) and Hartree-Fock/Møller-Plesset (HF/MP2) levels have been performed. Results have been assessed and evaluated against those obtained at the coupled cluster single-double (Triplet) (CCSD(T)) level of theory. The characteristics of the C-Br and O-Br bonds have been identified via analysis of the electrostatic potential, natural bond orbital (NBO), and quantum theory of atoms in molecules (QTAIM). Analysis of the electrostatic potential (ESP) maps enabled the quantitative characterization of the Br σ-holes. Its magnitude seems very sensitive to the environment and the charge accumulated in the adjacent centers. Some quantum topological parameters, namely Ñ2ρ, ellipticity at bond critical points and the Laplacian bond order, were computed and discussed. The potential energy function for internal rotation has been computed and Fourier transformed to characterize the conformational preferences and origin of the barriers. NBO energetic components for rotation about the C-Br and O-Br bonds as a function of torsion angle have been computed and displayed.

Experimental and theoretical investigation of the pyrolysis products of iminodiacetonitrile, (N≡CCH2)2NH.

The gas-phase FTIR study of the pyrolysis products of iminodiacetonitrile, (N≡CCH2)2NH has revealed the existence of C-cyanomethanimine, N≡CCH═NH, and ketenimine, CH2═C═NH. The former has two isomers: Z and E; while the later readily taumerizes to acetonitrile, CH3C≡N. A trapping/revaporization system has been used to purify C-cyanomethanimine. The analysis of the rotational structures of the IR medium resolution C-type CNH bend, ν6, and C═N torsional mode, ν10, has led to a conformational characterization of these isomers. The Z-isomer was shown to be the major product. This conjecture was supported by ab initio MO calculations that confirmed the relative total energy stability of the Z-isomer over its E-counterpart by 0.173 to 2.326 kJ/mol. The K values indicated that the equilibrium concentration of Z-C-cyanomethanimine amounts to up to three times that of E-C-cyanomethanimine. A further investigation using NBO technique proved the predilection of the Z-isomer. In addition it relates its provenance of preference to the remote nN6 → σ*C4-N5 interaction that stabilized it by 1.10 kcal/mol. A thorough theoretical investigation of the tautomerization reaction between ketenimine and acetonitrile will be published in a separate contribution.

A density functional theory investigation of the electronic structure and spin moments of magnetite.

We present the results of density functional theory (DFT) calculations on magnetite, Fe3O4, which has been recently considered as electrode in the emerging field of organic spintronics. Given the nature of the potential applications, we evaluated the magnetite room-temperature cubic [Formula: see text] phase in terms of structural, electronic, and magnetic properties. We considered GGA (PBE), GGA + U (PBE + U), and range-separated hybrid (HSE06 and HSE(15%)) functionals. Calculations using HSE06 and HSE(15%) functionals underline the impact that inclusion of exact exchange has on the electronic structure. While the modulation of the band gap with exact exchange has been seen in numerous situations, the dramatic change in the valence band nature and states near the Fermi level has major implications for even a qualitative interpretation of the DFT results. We find that HSE06 leads to highly localized states below the Fermi level while HSE(15%) and PBE + U result in delocalized states around the Fermi level. The significant differences in local magnetic moments and atomic charges indicate that describing room-temperature bulk materials, surfaces and interfaces may require different functionals than their low-temperature counterparts.

Does prop-2-ynylideneamine, HC≡CCH=NH, exist in space? A theoretical and computational investigation.

MP2, DFT and CCSD methods with 6-311++G** and aug-cc-pvdz basis sets have been used to probe the structural changes and relative energies of E-prop-2-ynylideneamine (I), Z-prop-2-ynylideneamine (II), prop-1,2-diene-1-imine (III) and vinyl cyanide (IV). The energy near-equivalence and provenance of preference of isomers and tautomers were investigated by NBO calculations using HF and B3LYP methods with 6-311++G** and aug-cc-pvdz basis sets. All substrates have Cs symmetry. The optimized geometries were found to be mainly theoretical method dependent. All elected levels of theory have computed I/II total energy of isomerization (ΔE) of 1.707 to 3.707 kJ/mol in favour of II at 298.15 K. MP2 and CCSD methods have indicated clearly the preference of II over III; while the B3LYP functional predicted nearly similar total energies. All tested levels of theory yielded a global II/IV tautomerization total energy (ΔE) of 137.3-148.4 kJ/mol in support of IV at 298.15 K. The negative values of ΔS indicated that IV is favoured at low temperature. At high temperature, a reverse tautomerization becomes spontaneous and II is preferred. The existence of II in space was debated through the interpretation and analysis of the thermodynamic and kinetic studies of this tautomerization reaction and the presence of similar compounds in the Interstellar Medium (ISM).

Local Renin-Angiotensin system in normal hematopoietic and multiple myeloma-related progenitor cells.

OBJECTIVE: The prominent functions of the local renin-angiotensin system (RAS) in primitive hematopoiesis further support the hypothesis that local autocrine bone marrow RAS could also be active in neoplastic hematopoiesis. The aim of this study is to examine critical RAS elements in normal CD34+ hematopoietic stem cells and multiple myeloma (MM)-related progenitor cells. MATERIALS AND METHODS: The study group comprised the total bone marrow cells (CBM) of 10 hematologically normal people, the CD34+ stem cell samples (CD34+CBM) of 9 healthy donors for allogeneic peripheral stem cell transplantation, and the CD34+ stem cell samples (CD34+MM) of 9 MM patients undergoing autologous peripheral stem cell transplantation. We searched for the gene expression of the major RAS components in healthy hematopoietic cells and myeloma cells by quantitative real-time polymerase chain reaction analysis. RESULTS: RENIN, angiotensinogen (ANGTS), and angiotensin converting enzyme-I (ACE I) mRNA expression levels of CBM were significantly higher than those in myeloma patients (p=0.03, p=0.002, and p=0.0008, respectively). Moreover, RENIN and ANGTS mRNA expression levels were significantly higher in CD34+ stem cell samples of healthy allogeneic donors compared to those in myeloma patients (p=0.001 and p=0.01). However, ACE I expression levels were similar in CD34+CBM and CD34+MM hematopoietic cells (p=0.89). CONCLUSION: Although found to be lower than in the CBM and CD34+CBM hematopoietic cells, the local RAS components were also expressed in CD34+MM hematopoietic cells. This point should be kept in mind while focusing on the immunobiology of MM and the processing of autologous cells during the formation of transplantation treatment protocols.

Therapeutic management of massive subcutaneous emphysema, bilateral pneumothorax and pneumomediastinum after anterior cordectomy for in situ vocal cord carcinoma - case report.

We present the case of a 70 year-old smoker patient, who was admitted in hospital for removal of a tumour located on the left vocal cord. After direct suspension laryngoscopy (with tumorbiopsy sampling), preliminary histopathological exam revealed an in situ carcinoma. At 2 weeks after histopathological confirmation, the left vocal cord was removed by anterior approach, under general anesthesia. In the first 24 hours after surgery, the patient presented an ischaemic stroke, with a deep coma and left hemiplegia, which necessitated mechanical ventilation and specific neurological treatment. Under mechanical ventilation, the patient developed massive subcutaneous emphysema, bilateral pneumothorax and pneumomediastinum,which required tracheostomy and bilateralpleural drainage, in order to limit suddenly installed respiratory insufficiency. After an 18-day interval of intensive care therapy,the patient was released at home, considered to be surgically cured and had a moderate remaining left brachial monoplegia,which was almost totally cured in the next six months.

Identifying novel therapeutic inhibitors to target FMS-like tyrosine kinase-3 (FLT3) against acute myeloid leukemia: a molecular docking, molecular dynamics, and DFT study.

Around 30% of acute myeloid leukemia (AML) patients have triggering mutations in Feline McDonough Sarcoma (FMS)-like tyrosine kinase 3 (FLT3), which has been suggested as a possible therapeutic candidate for AML therapy. Many tyrosine kinase inhibitors are available and have a wide variety of applications in the treatment of cancer by inhibiting subsequent steps of cell proliferation. Therefore, our study aims to identify effective antileukemic agents against FLT3 gene. Initially, well-known antileukemic drug candidates have been chosen to generate a structure-based pharmacophore model to assist the virtual screening of 217,77,093 compounds from the Zinc database. The final hits compounds were retrieved and evaluated by docking against the target protein, where the top four compounds have been selected for the analysis of ADMET. Based on the density functional theory (DFT), the geometry optimization, frontier molecular orbital (FMO), HOMO-LUMO, and global reactivity descriptor values have been evaluated that confirming a satisfactory profile and reactivity order for the selected candidates. In comparison to control compounds, the docking results revealed that the four compounds had substantial binding energies (-11.1 to -11.5 kcal/mol) with FLT3. The physicochemical and ADMET (adsorption, distribution, metabolism, excretion, toxicity) prediction results corresponded to the bioactive and safe candidates. Molecular dynamics (MD) confirmed the better binding affinity and stability compared to gilteritinib as a potential FLT3 inhibitor. In this study, a computational approach has been performed that found a better docking and dynamics score against target proteins, indicating potent and safe antileukemic agents, furthermore in-vivo and in-vitro investigations are recommended.Communicated by Ramaswamy H. Sarma.