Effect of constraint-induced movement therapy in reducing severity of mirror movements in children with unilateral spastic cerebral palsy.

To determine the effec t of constraint-induced movement therapy (CIMT ) in improving hand function and reduction in severity of mirror movements in children with unilateral spastic cerebral palsy who have mirror movement disorder. Spastic hemiplegic CP children of either gender, aged 6 to 16 years, with mirror movements of grade 1 and 2 who were able to make a gross grip, were included in this single arm feasibility study. CIMT was provided as an intervention to these children for six hours per day for 15 consecutive week days. Woods and Teuber criteria was applied for the assessment of mirror m oveme nt s. Pre - and po stinte rventi on assess ment results showed that there was improvemen t in the unimanual and bimanual hand func tion in CP-affected children (p<0.05) and reduction in the severity of mirror movements ( p<0 .05). Constra intinduced movement therapy improved hand function and reduced the severity of mirror movements in children with unilateral spastic cerebral palsy.

Imaging Spectrum of Severe Urinary Tract Infection Complications Presenting as a Seminal Vesicle Abscess, Prostatic Abscess, and Renal Abscess in Uncontrolled Diabetes Mellitus: A Case Report.

Urinary tract infections are more common and severe, and they carry worse outcomes for patients with type 2 diabetes mellitus. The infections are typically caused by resistant pathogens, leading to many complications. Various impairments in the immune system, poor metabolic control, and incomplete bladder emptying due to autonomic neuropathy may all contribute to the enhanced risk of urinary tract infections in these patients. We present an imaging spectrum of a severe urinary tract infection presenting as renal, prostatic, and seminal vesicle abscesses in a patient with uncontrolled diabetes mellitus.

Genetic diversity and haplotypes of Echinococcus granulosus isolated from cattle and buffaloes and first report of E. ortleppi (G5) in buffaloes in Pakistan based on mitochondrial cytochrome c oxidase subunit-1 gene (mt-CO1) markers.

Cystic echinococcosis (CE) is a parasitic disease that is caused by larval stage of Echinococcus granulosus tapeworm, one of the most important and neglected zoonotic disease. Although the echinococcosis is endemic in the neighboring countries, information regarding circulating genotypes of E. granulosus sensu lato is scarce in Pakistan. Therefore, the main purpose of this report was to contribute in molecular epidemiology and to find genetic variation and haplotypes of E. granulosus s.l. in cattle and buffalo isolates. To identify species circulating in country, parasite samples were collected from different slaughterhouses and butcher shops of two major cities, Rawalpindi and Peshawar located in Punjab and Khyber Pakhtunkhwa (KP) provinces, Pakistan, respectively. A total of 100 CE cyst samples were investigated from buffalo (n = 61), and cattle (n = 39) hosts. After genomic DNA extraction from individual cyst materials, mt-CO1 (875 bp) gene was amplified by PCR. After that, PCR products were electrophoresed on the agarose gel then purified and sequenced using forward primer. The sequences were trimmed (779 bp), aligned and matched with NCBI published sequences. E. granulosus s.s. (G1, G3) (71.4%; n = 20/28) was confirmed as the dominant species in buffalo and cattle. E. ortleppi (G5) (28.6%; n = 8/28) was recorded for the first time in both buffalo and cattle isolates from Rawalpindi. E. granulosus s.l. haplotype network showed single predominant haplotype, which comprised 40% of population. Tajima's D and Fu's Fs were negative and significant for E. ortleppi (G5), suggesting population expansion in Pakistan. Therefore, more studies using isolates of E. granulosus s.l. from various locations and intermediate hosts across Pakistan will add new data on molecular epidemiology and genotyping for effective control strategies of CE in Pakistan.

Investigating the role of Sterol C24-Methyl transferase mutation on drug resistance in leishmaniasis and identifying potential inhibitors.

Leishmaniasis is a fatal disease caused by the leishmania parasite. For the survival of the leishmania parasite, Sterol C24-Methyl Transferase (SMT) is essential which is an enzyme of the ergosterol pathway. SMT protein mutation is responsible for Amphotericin-B drug resistance in Leishmania, which is the main treatment for visceral leishmaniasis. Amphotericin-B resistance is caused by three mutated residues V131I, V321I and F72C. The underlying mechanisms and structural changes in SMT enzymes responsible for resistance due to mutation are still not well understood. In the current study, the potential mechanism of resistance due to these mutations and the structure variation of wild and mutant SMT proteins were investigated through molecular dynamics simulations and molecular docking analysis. The results showed that AmB established strong bonding interaction with wild SMT as compare to mutants SMT. The binding energy calculation showed that binding energy of AmB with mutants SMT increases as compare to the wild SMT. Further structural based virtual screening was carried out to design potential inhibitors for the mutant SMT. On the basis of structural-based virtual screening four inhibitors (SANC01057, SANC00882, SANC00414, SANC01047) were computationally identified as potential mutant SMT (F72C) inhibitors. This work provides valuable information for improved management of drug resistant Leishmaniasis.Communicated by Ramaswamy H. Sarma.

Ionic liquid-based dispersive liquid-liquid microextraction of succinic acid from aqueous streams: COSMO-RS screening and experimental verification.

In the present investigation, a total of 108 combinations of ionic liquids (ILs) were screened using the conductor-like screening model for real solvents (COSMO-RS) with the aid of six cations and eighteen anions for the extraction of succinic acid (SA) from aqueous streams through dispersive liquid-liquid microextraction (DLLME). Using the screened ILs, an ionic liquid-based DLLME (IL-DLLME) was developed to extract SA and the role of different reaction parameters in the effectiveness of IL-DLLME approach was investigated. COSMO-RS results suggested that, quaternary ammonium and choline cations form effective IL combinations with [OH¯], [F¯], and [SO42¯] anions due to hydrogen bonding. In view of these results, one of the screened ILs, tetramethylammonium hydroxide [TMAm][OH] was chosen as the extractant in IL-DLLME process and acetonitrile was adopted as the dispersive solvent. The highest SA removal efficiency of 97.8% was achieved using 25 µL of IL [TMAm][OH] as a carrier and 500 µL of acetonitrile as dispersive solvent. The highest amount of SA was extracted with a stir time of 20 min at 300 rpm, followed by centrifugation for 5 min at 4500 rpm. Overall, the findings showed that IL-DLLME is efficient in extracting succinic acid from aqueous environments while adhering to the first-order kinetics.

Angiotensin-Converting Enzyme and Hypertension: A Systemic Analysis of Various ACE Inhibitors, Their Side Effects, and Bioactive Peptides as a Putative Therapy for Hypertension.

Hypertension is a major risk factor for heart attack, produce atherosclerosis (hardening of the arteries), congestive heart failure, stroke, kidney infection, blindness, end-stage renal infection, and cardiovascular diseases. Many mechanisms are involved in causing hypertension, i.e., via calcium channels, alpha and beta receptors, and the renin-angiotensin system (RAS). RAS has an important role in blood pressure control and is also involved in the metabolism of glucose, homeostasis, and balance of electrolytes in the body. The components of RAS that are involved in the regulation of blood pressure are angiotensinogen, Ang I (angiotensin I), Ang II (angiotensin II), ACE (angiotensin-converting enzyme), and ACE 2 (angiotensin-converting enzyme 2). These components provide for relevant therapeutic targets for the treatment of hypertension, and various drugs are commercially available that target individual components of RAS. Angiotensin receptor blockers (ARBs) and ACE inhibitors are the most popular among these drugs. ACE is chosen in this review as it makes an important target for blood pressure control because it converts Ang I into Ang II and also acts on the vasodilator, bradykinin, to degrade it into inactive peptides. This review highlights various aspects of blood pressure regulation in the body with a focus on ACE, drugs targeting the components involved in regulation, their associated side effects, and a need to shift to alternative therapy for putative hypertension treatment in the form of bioactive peptides from food.

Evaluating ionic liquids for its potential as eco-friendly solvents for naproxen removal from water sources using COSMO-RS: Computational and experimental validation.

An emerging contaminant of concern in aqueous streams is naproxen. Due to its poor solubility, non-biodegradability, and pharmaceutically active nature, the separation is challenging. Conventional solvents employed for naproxen are toxic and harmful. Ionic liquids (ILs) have attracted great attention as greener solubilizing and separating agent for various pharmaceuticals. ILs have found extensive usage as solvents in nanotechnological processes involving enzymatic reactions and whole cells. The employment of ILs can enhance the effectiveness and productivity of such bioprocesses. To avoid cumbersome experimental screening, in this study, conductor like screening model for real solvents (COSMO-RS) was used to screen ILs. Thirty anions and eight cations from various families were chosen. Activity coefficient at infinite dilution, capacity, selectivity, performance index, molecular interactions using σ-profiles and interaction energies were used to make predictions about solubility. According to the findings, quaternary ammonium cations, highly electronegative, and food-grade anions will form excellent ionic liquid combinations for solubilizing naproxen and hence will be better separating agents. This research will contribute easy designing of ionic liquid-based separation technologies for naproxen. In different separation technologies, ionic liquids can be employed as extractants, carriers, adsorbents, and absorbents.

Ionic Liquid-Based Green Emulsion Liquid Membrane for the Extraction of the Poorly Soluble Drug Ibuprofen.

Ibuprofen (Ibf) is a biologically active drug (BADs) and an emerging contaminant of concern (CECs) in aqueous streams. Due to its adverse effects upon aquatic organisms and humans, the removal and recovery of Ibf are essential. Usually, conventional solvents are employed for the separation and recovery of ibuprofen. Due to environmental limitations, alternative green extracting agents need to be explored. Ionic liquids (ILs), emerging and greener alternatives, can also serve this purpose. It is essential to explore ILs that are effective for recovering ibuprofen, among millions of ILs. The conductor-like screening model for real solvents (COSMO-RS) is an efficient tool that can be used to screen ILs specifically for ibuprofen extraction. The main objective of this work was to identify the best IL for the extraction of ibuprofen. A total of 152 different cation-anion combinations consisting of eight aromatic and non-aromatic cations and nineteen anions were screened. The evaluation was based upon activity coefficients, capacity, and selectivity values. Furthermore, the effect of alkyl chain length was studied. The results suggest that quaternary ammonium (cation) and sulfate (anion) have better extraction ability for ibuprofen than the other combinations tested. An ionic liquid-based green emulsion liquid membrane (ILGELM) was developed using the selected ionic liquid as the extractant, sunflower oil as the diluent, Span 80 as the surfactant, and NaOH as the stripping agent. Experimental verification was carried out using the ILGELM. The experimental results indicated that the predicted COSMO-RS and the experimental results were in good agreement. The proposed IL-based GELM is highly effective for the removal and recovery of ibuprofen.

Combined Effects of Fluoride and Arsenic on Mitochondrial Function in the Liver of Rat.

Biochemical and/or molecular mechanisms of arsenic or fluoride toxicity in experimental animals have been widely investigated in the recent past. However, their combined effects on target cells/organelle are poorly understood. The present study was executed to delineate their combined effects on mitochondrial function in the liver of rat. Female Wistar rats (140 ± 20 g) were force fed individually or in combination with sodium arsenate (4 mg/kg body weight) and sodium fluoride (4 mg/kg body weight) for 90 days. Thereafter, established markers of mitochondrial function viz. mitochondrial lipid peroxidation, oxidative phosphorylation, ATPase, succinic dehydrogenase, and caspase-3 activity were determined. Cytochrome C release and oxidative DNA damage were also estimated in the liver of respective groups of rats. The study showed significant differences in these results amongst the three groups. Observations on parameters viz. LPO, cytochrome-C, caspase-3, and 8-OHdG suggested an antagonistic relationship between these two elements. Results on ATPase, SDH, and ADP:O ratio indicated synergism. It is concluded that AsIII + F in combination may express differential effects on signalling pathways and proapoptotic/antiapoptotic proteins/genes that contribute to liver cell death. Interaction of As and F with mitochondria.

Emerging Treatment Options for Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is characterized as a chronic, multifactorial disease and is the leading cause of irreversible blindness. Advanced AMD is classified as neovascular (wet) AMD and non-neovascular (dry) AMD. Dry AMD can progress to a more advanced form that manifests as geographic atrophy (GA), which significantly threatens vision, leading to progressive and irreversible loss of visual function. There are currently no approved therapeutics commercially available for GA patients. However, data from various clinical trials have demonstrated favorable results with significant reduction in GA lesion growth. This review furthers the understanding of the pathophysiology of GA, as well as current clinical trial data on investigational therapeutics.

Screening of ionic liquids as green entrainers for ethanol water separation by extractive distillation: COSMO-RS prediction and aspen plus simulation.

Ionic liquids (ILs) have been demonstrated as promising alternatives to conventional entrainers in separation of azeotropic mixtures mostly investigating phase equilibrium and process design scenarios. However, proper selection of ILs for a specific task always remains challenging. Hence a simulation tool, i.e. conductor like screening model for real solvents (COSMO-RS) was applied to address this challenge. Furthermore, screened ILs were simulated as entrainers for ethanol water separation by extractive distillation. The current study also aims to demonstrate a systematic approach to retrofit existing processes, by employing ILs as green entrainers. Screening of twenty-five (25) ILs was carried out using COSMO-RS to select suitable ILs as green entrainers based on activity coefficient, capacity and selectivity. Results illustrated that tetramethylammonium chloride ([TMAm][Cl]) due to its strong hydrogen bonding ability was found to be the best ILs entrainer. Moreover, in order to reduce the operating costs without compromising desired product purity (ethanol purity ≥99.5% in top product), the selected ILs (8 kg/h) in a mixture with ethylene glycol (72 kg/h) were simulated using Aspen plus v.11. The simulation results revealed that by combining tetramethylammonium chloride (2 kg/h) with ethylene glycol (78 kg/h) reduced 7.26 tons of CO2 emissions/year through heat integration by saving 1.49*108 kJ/year energy besides minimizing operating costs. In conclusion, the systematic selection of ILs as green entrainers in combination with ethylene glycol and then the appropriate simulation of the whole system will ultimately reduce the cost of the separation process and reduce the emission of greenhouse gases as well utilization of toxic conventional entrainers.

Breast Cancer Management Consensus By The Society of Surgeons and Surgical Oncology Society of Pakistan.

The Society of Surgeons of Pakistan and The Society of Surgical Oncology of Pakistan with factions from various major centres comprising of surgical oncology, medical and radiation oncology collaborated to reach consensus on breast cancer management guidelines and a framework of "good practice" minimum standards of care. The aim of the task force was to enhance treatment standards, which have a direct correlation with improving patient mortality and morbidity and long-term survival whilst taking into consideration economic limitations of access to leading centers of excellence as well as minimum expertise required in health care. These multidisciplinary guidelines, whilst not exhaustive, aim to provide an algorithm of care for breast cancer patients at tertiary care centres and district level hospitals to provide most appropriate treatment.

Water-Soluble Carbon Monoxide-Releasing Molecules (CORMs).

Carbon monoxide-releasing molecules (CORMs) are promising candidates for producing carbon monoxide in the mammalian body for therapeutic purposes. At higher concentrations, CO has a harmful effect on the mammalian organism. However, lower doses at a controlled rate can provide cellular signaling for mandatory pharmacokinetic and pathological activities. To date, exploring the therapeutic implications of CO dose as a prodrug has attracted much attention due to its therapeutic significance. There are two different methods of CO insertion, i.e., indirect and direct exogenous insertion. Indirect exogenous insertion of CO suggests an advantage of reduced toxicity over direct exogenous insertion. For indirect exogenous insertion, researchers are facing the issue of tissue selectivity. To solve this issue, developers have considered the newly produced CORMs. Herein, metal carbonyl complexes (MCCs) are covalently linked with CO molecules to produce different CORMs such as CORM-1, CORM-2, and CORM-3, etc. All these CORMs required exogenous CO insertion to achieve the therapeutic targets at the optimized rate under peculiar conditions or/and triggering. Meanwhile, the metal residue was generated from i-CORMs, which can propagate toxicity. Herein, we explain CO administration, water-soluble CORMs, tissue accumulation, and cytotoxicity of depleted CORMs and the kinetic profile of CO release.

Metal-Organic Precursor Synthesis, Structural Characterization, and Multiferroic Properties of GdFeO3 Nanoparticles.

GdFeO3 nanoparticles were fabricated by a facile metal-organic precursor method using citric acid as a complexing agent. The phase purity and structural analysis by powder X-ray diffraction and FTIR studies indicates that the material is highly crystalline with an orthorhombic structure. Electron microscopic (TEM and SEM) studies of rare earth ferrites reveal worm-shaped nanoparticles with an average grain size of 95 nm. The high-resolution TEM study provides an insightful image, which shows an interplanar spacing of approximately 0.12 nm that corresponds to the (112) crystalline plane. A high surface area of 231.5 m2 g-1 has been achieved with a mesoporous texture, which in turn gives a high dielectric constant. Well-defined hysteresis is obtained with a saturation magnetization of 17.5 emu g-1, remanent magnetization of 3.9 emu g-1, and coercive field of -446 Oe. Room-temperature ferroelectricity in GdFeO3 nanoparticles has been found for the first time with no leaky current and hence may be used in multistate memory devices.

Vegetable Oil-Ionic Liquid-Based Emulsion Liquid Membrane for the Removal of Lactic Acid from Aqueous Streams: Emulsion Size, Membrane Breakage, and Stability Study.

In this study, we present a highly stable vegetable oil ionic liquid (IL)-based emulsion liquid membrane (VOILELM) for the removal of lactic acid from water streams. The system developed as a part of this work comprises a non-ionic surfactant Span 80, sodium hydroxide as an internal stripping agent, sunflower canola oil as a green diluent, and IL-tetramethylammonium acetate [TMAm][Ac]-as a carrier. VOILELM stability was evaluated in terms of breakage, emulsion diameter, and standalone stability. The effect of various parameters, namely, concentration of the surfactant, concentration of the internal stripping agent, concentration of the carrier, phase ratio, homogenizer speed, and homogenization time, on the VOILELM stability was studied. The results revealed that VOILELM was highly stable, with 1.34% minimum breakage, 1.16 µm emulsion diameter, and 131 min standalone stability. The optimal process parameters were 0.1 wt % Span 80, 0.1 M NaOH, 0.3 wt % IL, 0.25 phase ratio, 5000 rpm homogenizer speed, and 5 min homogenization time. At these optimized conditions, 96.08% lactic acid extraction efficiency was achieved. Thus, a highly effective VOILELM was developed, with minimal breakage and emulsion diameter and maximum stability.

Sentinel Lymph Node Mapping in Breast Cancer: Initial Experience of a Multidisciplinary Team.

INTRODUCTION: Breast cancer is one of the leading causes of cancer-related deaths in women; it is the most frequently diagnosed cancer in women in the United States with a lifetime risk of dying of about 3.4%. Regional lymph node involvement is quite early in breast carcinoma and axillary lymph node metastasis is an important predictor of recurrence and survival, particularly in invasive ductal histology of breast carcinoma. Localization of sentinel lymph node/nodes followed by frozen section and histopathological evaluation helps to prevent unnecessary axillary nodal dissection and, hence, reduces associated post-surgical morbidity. Sentinel nodes are the first ones to receive lymph-borne metastatic cells and, hence, lymphoscintigraphy followed by biopsy is quite reliable to detect nodal metastasis, particularly at an early stage (I, II) of breast cancer. METHODS: Here we will share our experience of introducing procedure, personnel training, and workflow of sentinel lymph node lymphoscintigraphy in breast cancer patients at our cancer institute to help other centers establish programs for this study. RESULTS: Initially, 10 procedures were performed, all of which were successful in the localization of sentinel nodes and played a substantial part in the surgical planning of breast cancer. Planar lymphoscintigraphy and single-photon emission computerized tomography (SPECT)-CT images of our first patient revealed radiotracer avidity in the lymph node in the ipsilateral axilla, which was later on diagnosed as metastatic resulting in axillary nodal clearance. CONCLUSIONS:  In multidisciplinary/closely-placed surgical, pathological, and hybrid imaging facility settings, lymphoscintigraphy provides a quick, accurate, and better way of nodal localization leading to correct surgical decision-making. In addition to planar imaging, SPECT-CT acquisition significantly improves the specificity of the lymphoscintigraphy procedure, which is beneficial for patients to avoid false-positive results, thus saving breast cancer patients from potential adverse effects of surgery.

Modified, Solvothermally Derived Cr-doped SnO2 Nanostructures for Enhanced Photocatalytic and Electrochemical Water-Splitting Applications.

Cr-doped SnO2 nanostructures with a dopant concentration ranging from 1 to 5% have been successfully prepared using low-temperature modified solvothermal synthesis. The as-prepared nanoparticles showed a rutile tetragonal structure with a rough undefined morphology having no other elemental impurities. The particle shape and size, band gap, and specific surface area of the samples were investigated by scanning electron microscopy, transmission electron microscopy (TEM), high-resolution TEM, UV-visible diffused reflectance spectroscopy, and Brunauer-Emmett-Teller surface area studies. The optical band gap was found in the range of 3.23-3.67 eV and the specific surface area was in the range of 108-225 m2/g, which contributes to the significantly enhanced photocatalytic and electrochemical performance. Photocatalytic H2 generation of as-prepared Cr-doped SnO2 nanostructures showed improved effect of the increasing dopant concentration with narrowing of the band gap. Electrochemical water-splitting studies also stressed upon the superiority of Cr-doped SnO2 nanostructures over pristine SnO2 toward hydrogen evolution reaction and oxygen evolution reaction responses.

Effect of temperature & humdity on population dynamics of insects' pest complex of cotton crop.

The current study was directed to investigate the effect of temperature and humidity on insect pest complex of cotton. This study was carried out on the farmer field of a farmer of MouzaMehraywala tehsil and district Rajanpur southern part of the Punjab, Pakistan (29.1044° N, 70.3301° E) in the month of May, 2019 to November 2019. The climatic conditions of the study site were; a Rajanpur lie on 96m above sea level Rajanpur has a desert climate. During the year, there is virtually no rainfall. The average temperature in Rajanpur is 26.0°C | 78.8°F. Precipitation here is about 205 mm / 8.1 inch per year. Our results indicate that's the correlation of temperature (minimum and maximum), humidity (minimum and maximum), rainfall and weather condition (clear or cloud), it is clear that except temperature there is a positive correlation of jassid population. While among the relation of jassid with different factor there is very weak relation with jassid population regarding temperature (-0.001), the relation of humidity, rainfall and sky condition with jassid population is positive and moderate (0.520, 0.668 & 0.575 respectively), while the relation of jassid population among these factor is significant except temperature. The results indicate that's the correlation of temperature, humidity, rainfall and weather condition, it is clear that there is positive correlation of thrips population. While among the relation of thrips with different factor there is very weak relation of thrips population with temperature (.103), the relation of humidity, rainfall and sky condition with thrips population is positive and moderate (.515.751& .577 respectively), while the relation thrips population among these factor is significant except temperature. The results indicate that's correlation of temperature, humidity, rainfall and weather condition, it is clear that there is positive correlation of Whitefly population. While among the relation of Whitefly with different factors there is very moderate relation of Whitefly population with temperature (.076), the relation of humidity, rainfall and sky condition with Whitefly population is negative and moderate (-.051.-.368 & -.559 respectively), while the relation Whitefly population among these factor is significant except temperature.

Hydrophilic CO-Releasing Material of PEGlyated Ruthenium Carbonyl Complex.

The poor water-solubility and instability of Ru(II) carbonyl complex hamper the therapeutic application as CO releasing materials (CO-RMs). To enhance the hydrophilicity and bio-utility of CO, a robust Ru(I) carbonyl sawhorse skeleton was grafted with water-soluble PEGylated sidearm. In this case, 12 PEGylated sawhorse Ru2(CO)4 complexes were prepared with satisfactory yields and characterized by IR and 1H- and 13C- NMR. X-ray diffraction analysis of CO-RM 8, 13 and 14 revealed the featured diruthenium sawhorse skeleton and PEGylated axial ligands. The flask-shaking method measures the water-solubility of CO-RMs, indicating that both bridging carboxylate ligands and PEGlyated axial ligands regulate the hydrophilicity of these CO-RMs. Under photolysis conditions, CO-RM 4-13 sustainable released therapeutic amounts of CO in the myoglobin assay. The correlation of the CO release kinetics and hydrophilicity of CO-RMs demonstrated that the more hydrophilic CO-RM released CO faster. The biological test found that the low cytotoxic CO-RM 4 showed a specific anticancer activity toward HT-29 tumour cells.