Mapping the meltdown behavior of frozen dairy desserts.

The meltdown test is an efficient tool widely and commonly used to characterize structural changes in frozen desserts resulting from different ingredients and processing conditions. The meltdown is commonly determined by a gravimetric test, and it is used to obtain the onset (Mon), rate (Mrate), and maximum (MMax) meltdown. However, these parameters are calculated ambiguously due to inconsistencies in the methodology. This work aims to model the meltdown curves (weight vs. time) of different commercial frozen dessert samples (36 commercial samples). Samples of commercial frozen desserts (40-60 g) was placed on a 304 stainless wire cloth (1.50 mm opening size and 52% open area) suspended ∼15 cm above an analytical balance, and the dripped portion of the melted sample was continuously recorded throughout the duration of the test. The meltdown test was conducted at room temperature. Each meltdown test generated between 3,000 to 4,000 data points and was modeled using 4 equations: the logistic model, the Gompertz model, the Richard model, and the Hill model. All the meltdown curves were sigmoidal in shape, regardless of the type of frozen dessert. The experimental meltdown curves were adequately represented by the logistic model, judging by several criteria (R2 = 0.999, RAdj2 = 0.999, Akaike information criterion = 6,582, and F-value = 1.88 × 106). Thus, the logistic model was shown to be an effective tool for predicting the meltdown curves of frozen desserts, and it can be used to unambiguously define Mon, Mrate, and MMax. Moreover, a dimensionless response (meltdown behavior, MBe) that combines Mon, Mrate, and MMax was developed and used for mapping the meltdown of different commercial frozen desserts.

Response Surface Methodology (RSM) approach to formulate and optimize the bilayer combination tablet of Tamsulosin and Finasteride.

An orally administered bilayer tablet with Tamsulosin (TAM) as the sustained release (SR) and Finasteride (FIN) as immediate release (IR) was manufactured. A response surface methodology was employed to formulate bilayer tablets with individual release layers, i.e., sustained and immediate release (SR and IR). Independent variables selected in both cases comprise hydroxypropyl methylcellulose (HPMC) as SR polymer, and avicel PH102 in the inner layer while Triacetin and talc in the outer layer, respectively. Tablets were prepared by direct compression, a total of 11 formulations were prepared for inner layer TAM, and 9 formulations for outer layer FIN were designed; these formulations were evaluated for hardness, friability, thickness, %drug content, and %drug release. A central composite design was employed in response surface methodology to design and optimize the formulation. The percentage of drug released was evaluated by in-vitro USP dissolution method of optimized formulation for 0.5, 2, and 6 hrs, and results were 24.63, 52.96, and 97.68 %, respectively. Drug release data was plotted in various kinetic models using a D.D solver, where drug release was first order that is concentration dependent and was best explained by Korsmeyer-Peppa kinetics, as the highest linearity was observed (R2 = 0.9693). However, a very close relationship was also noted with Higuchi kinetics (R2 = 0.9358). The mechanism of drug release was determined through the Korsmeyer model, and exponent "n" was found to be 0.4, indicative of an anomalous diffusion mechanism or diffusion coupled with erosion.

An unprecedented route to achieve persistent 1H-azirine.

1H-azirine, a highly reactive, antiaromatic, and unstable tautomer of the aromatic, stable, and (sometimes) isolable 2H-azirine, is stabilized, both thermodynamically and kinetically, via an unprecedented route, where the latter serves as the precursor-exploiting electronic and steric elements. Our density functional theory results invite experimentalists to realize isolable 1H-azirine.

Solid lipid nanoparticles: a versatile approach for controlled release and targeted drug delivery.

Solid Lipid Nanoparticles (SLN), the first type of lipid-based solid carrier systems in the nanometer range, were introduced as a replacement for liposomes. SLN are aqueous colloidal dispersions with solid biodegradable lipids as their matrix. SLN is produced using processes like solvent diffusion method and high-pressure homogenization, among others. Major benefits include regulated release, increased bioavailability, preservation of peptides and chemically labile compounds like retinol against degradation, cost-effective excipients, better drug integration, and a broad range of applications. Solid lipid nanoparticles can be administered via different routes, such as oral, parenteral, pulmonary, etc. SLN can be prepared by using high shear mixing as well as low shear mixing. The next generation of solid lipids, nanostructured lipid carriers (NLC), can reduce some of the drawbacks of SLN, such as its restricted capacity for drug loading and drug expulsion during storage. NLC are controlled nanostructured lipid particles that enhance drug loading. This review covers a brief introduction of solid lipid nanoparticles, manufacturing techniques, benefits, limitations, and their characterization tests.

Qatar genome: Insights on genomics from the Middle East.

Despite recent biomedical breakthroughs and large genomic studies growing momentum, the Middle Eastern population, home to over 400 million people, is underrepresented in the human genome variation databases. Here we describe insights from Phase 1 of the Qatar Genome Program with whole genome sequenced 6047 individuals from Qatar. We identified more than 88 million variants of which 24 million are novel and 23 million are singletons. Consistent with the high consanguinity and founder effects in the region, we found that several rare deleterious variants were more common in the Qatari population while others seem to provide protection against diseases and have shaped the genetic architecture of adaptive phenotypes. These results highlight the value of our data as a resource to advance genetic studies in the Arab and neighboring Middle Eastern populations and will significantly boost the current efforts to improve our understanding of global patterns of human variations, human history, and genetic contributions to health and diseases in diverse populations.

Synthesis and characterization of self-assembling chitosan-based nanoparticles.

Chitosan (CHT) based biodegradable nanovectors were synthesized and modified with poly ethylene glycol 4000 (PEG-4000). CHT having medium molecular weight with 75% to 85% deacetylation was phthaloylated with phthalic anhydride, followed by PEGylation using PEG-4000. After confirmation of successful PEGylation by fourier transforminfra red spectroscopy (FTIR), the modified polymer was further processed to develop the nanocarrier using ionic gelation method by the addition of sodium tripolyphosphate (NaTPP). The prepared nanocarriers were subjected to physicochemical evaluation. The surface morphology of the particles was observed under scanning electron microscope (SEM), and particle size by dynamic light scattering (DLS) method, which was about 159-170nm in diameter. The zeta potential of the prepared nanovectors was +0.907mV which was due to cationic nature of nanovectors. The cell viability studies were also conducted to find the suitability of the carrier for in-vivo application, using liver cancerous cells (Hep G2). The findings have disclosed the concentration dependent activities of the particles, as viability of the cell was shown to be decreased with the increase in the concentration of the particles. Conclusively, the study was successful in determining the toxicity profile of these nanovectors as these were proved non-toxic at specific concentration.

Acute cerebellitis following SARS-CoV-2 infection: A case report and review of the literature.

Novel coronavirus disease (COVID-19) first described in Wuhan, China in December 2019, has rapidly spread across the world and become a global public health emergency. Literature on the neurological manifestations of COVID-19 is limited. We report a 24-year-old male, who presented with vertigo, dysarthria, and bradyphrenia 3 weeks after being diagnosed with COVID-19 on nasopharyngeal reverse transcription polymerase chain reaction. The patient was diagnosed with acute cerebellitis based on magnetic resonance imaging features and showed improvement posttreatment with intravenous methylprednisone for 5 days. The scope of this article is to highlight the importance of early identification of neurological symptoms and timely management as the outcomes may be catastrophic.

Systematic Design of a Frustrated Lewis Pair Containing Methyleneborane and Carbene for Dinitrogen Activation.

Activation of atmospherically abundant dinitrogen (N2) by metal-free species under mild reaction conditions has been one of the most challenging areas in chemistry for decades. Very recent but limited progress in N2 activation by boron species, including two-coordinated borylene and methyleneborane and three-coordinated borole and borane, has been made toward metal-free N2 activation. Here, we systematically probe an experimentally viable frustrated Lewis pair (FLP) containing two moieties (methyleneborane and carbene) for N2 activation via density functional theory (DFT) calculations, which has proven to be an efficient approach for N2 activation in a thermodynamically and kinetically favorable manner. Aromaticity is found to play a crucial role in stabilization of the product. This study could be a valuable alternative for the development of metal-free N2 activation chemistry, highlighting great potential of FLP for N2 activation and functionalization.

Adapting Clinical Practice of Thrombolysis for Acute Ischemic Stroke Beyond 4.5 Hours: A Review of the Literature.

Several clinical trials have demonstrated that advanced neuroimaging can select patients for recanalization therapy in an extended time window. The favorable functional outcomes and safety profile of these studies have led to the incorporation of neuroimaging in endovascular treatment guidelines, and most recently, also extended to decision making on thrombolysis. Two randomized clinical trials have demonstrated that patients who are not amenable to endovascular thrombectomy within 4.5 hours from symptoms discovery or beyond 4.5 hours from the last-known-well time may also be safely treated with intravenous thrombolysis and have a clinical benefit above the risk of safety concerns. With the growing aging population, increased stroke incidence in the young, and the impact of evolving medical practice, healthcare and stroke systems of care need to adapt continuously to provide evidence-based care efficiently. Therefore, understanding and incorporating appropriate screening strategies is critical for the prompt recognition of potentially eligible patients for extended-window intravenous thrombolysis. Here we review the clinical trial evidence for thrombolysis for acute ischemic stroke in the extended time window and provide a review of new enrolling clinical trials that include thrombolysis intervention beyond the 4.5 hour window.

Very early onset inflammatory bowel disease: Spectrum of clinical presentation, diagnostic tools and outcome in children.

OBJECTIVE: To explore the spectrum of presentation, underlying monogenetic defects and outcome in very early onset inflammatory bowel disease (VEO-IBD). METHOD: The prospective, observational study was conducted at the Children's Hospital, Lahore, Pakistan, from January 2017 to December 2018, and comprised children developing features of inflammatory bowel disease aged <6 years. Data included demography, clinical presentation, diagnostic tools and outcome. Data was analysed using SPSS 21. RESULTS: Of the 60 children with relevant symptoms, 26(43.3%) were diagnosed as having very early onset inflammatory bowel disease. Of them, 13(50%) had underlying monogenic defect, and 16(61.5%) had ulcerative colitis. There were 22(84.6%) males with median age of 1.5(11) months in monogenic inflammatory bowel disease versus 24(43) months for non-monogenic inflammatory bowel disease (p<0.05). In the monogenic group, isolated rectal bleeding was the major presentation 13(100%) versus non-monogenic who presented mainly with failure to thrive 13(100%). Upper and lower endoscopies with histopathology had good diagnostic yield and inflammatory infiltrates on the biopsied tissues were the major findings. Mutations detected among the subjects were XIAP, PRKDC, PIK3CD, RAG-1, LRBA, DOCK8, TTC7, MEFV and EPCAM. Mortality was significantly higher in the monogenic group 7(54%) than in the non-monogenic group 2(15%) (p<0.05). CONCLUSIONS: Very early onset inflammatory bowel disease should be suspected when conventional management fails to rectify common disease mimickers. Testing for underlying immunological defect and genetic mutation would be helpful for managing these rare disorders.

Comparison of mean operative time in patients undergoing Ho: YAG laser lithotripsy and pneumatic lithotripsy in ureterorenoscopy for ureteric calculus.

OBJECTIVE: To compare the mean operative time (MOT) in patients undergoing Ho: YAG laser lithotripsy (LL) and pneumatic lithotripsy (PL) for ureteric stones. METHODS: This randomized study was conducted at Armed Forces Institute of Urology (AFIU) Rawalpindi, Pakistan from July 2016 to November 2018. Non probability consecutive sampling technique utilized to enroll 60 patients of both gender aged 18-60 years, having ureteric calculus ≤1.5cm. Randomization was done into group I (LL) and II (PL) via computer generated number tables. Six Consultant Urologists performed surgeries under spinal anesthesia utilizing Swiss Lithoclast® Master (EMS+ S.A. Switzerland) in group II and holmium laser fiber (365µm, 8-10Hz, 9.6-16W, 2100nm wavelength) in group I respectively. MOT was noted from insertion of cystoscope till removal out of meatus. Data obtained was analyzed through IBM SPSS 24.0. RESULTS: Analysis involved 60 patients (30 each group) having similar baseline characteristics (age, gender, laterality, location). There was statistically significant different MOT between LL & PL (25.48±6.99 vs 34.83± 7.47 minutes, p < 0.001). Data stratification with respect to age, gender, laterality and stone location revealed similar trend. Lithotripsy technique significantly affected MOT (p < 0.001) on Multiple Linear Regression Analysis. CONCLUSIONS: Ho: YAG LL is an efficient technique when compared with PL in terms of MOT for ureteric stones.

Formulation and evaluation of sustained release ocular inserts of betaxolol hydrochloride using arabinoxylan from Plantago ovata.

The purpose of the current studies was to develop ocular insert of betaxolol hydrochloride (BXH), using arabinoxylan (AX) as a film former. The inserts were prepared by sandwiching I mg of BXH between two films of AX. Six different formulations of ocular inserts were prepared in such a way that first three formulations contained varying concentrations of AX along with glycerol as plasticizer, whereas, rest of the formulations were added with 0.5mg of sodium alginate, sandwiched between two films of AX along with 1mg of BXH. Chemical compatibilities of the ingredients were assessed by using FTIR. Prepared ocular inserts were subjected to various physicochemical characterizations. The dissolution studies showed that ocular inserts containing sodium alginate with the AX showed sustained release effect better than the formulations with AX alone. Addition of sodium alginate resulted in inhibition of sudden release in initial phase and further sustained the release of drug from ocular inserts. Ocular inserts were pH compatible to the eyes as well as there was no interaction among the drug and excipients, suggesting that the selected excipients were suitable for the development of sustained release ocular inserts of BXH.

Screening Borane Species for Dinitrogen Activation.

Activation of the strongest triplet bond in molecular nitrogen (N2) under mild conditions is particularly challenging. Recently, its fixation and reduction were achieved by highly reactive dicoordinated borylene species at ambient conditions, ripping the limits of harsh reaction conditions by metallic species. Less reactive species with a facile preparation could be desirable for next-generation N2 activation. Now density functional theory calculations reveal that tricoordinated boranes could be a potential candidate of N2 activation/functionalization. As composites of an intramolecular frustrated Lewis pair (FLP), optimal and realistic boranes are screened out to activate N2 in a significantly favorable manner (both thermodynamically and kinetically). The significant thermodynamic stabilities of the FLP-N2 adducts as well as the low activation barriers could be particularly interesting for the development of borane-based FLP chemistry applied in N2 activation.

Theoretical study on the stability and aromaticity in silapentafulvenes towards triplet ground state species.

Pentafulvenes are dipolar hydrocarbons since they shift their π-electrons to achieve Hückel aromaticity and thus the electron donating groups at the exocyclic position can enhance their aromaticity. Silapentafulvenes are analogues of pentafulvene formed by the replacement of the carbon atoms at the exocyclic C[double bond, length as m-dash]C double bond with a silicon atom in pentafulvene. It remains unclear how the aromaticity of 5-silapentafulvenes and 6-silapentafulvenes can be changed due to the polarization of the C[double bond, length as m-dash]Si double bond. Here we perform density functional theory calculations and reveal the increased aromatic character in 6-silapentafulvenes and the reduced aromaticity of 5-silapentafulvenes in the ground state. In addition, the origin of the relative thermodynamic stability of the silapentafulvene isomers can be attributed to the bond dissociation energy (BDE) of the exocyclic bond. More interestingly, some triplet ground state 5-silapentafulvene species are predicted by introducing amino groups on the ring, which is supported by the coupled cluster calculations. Our findings could be useful for experimentalists to realize silaaromatics.

Expanding Acute Stroke Care in Rural America: A Model for Statewide Success.

Background: The state of West Virginia (WV) is often seen as a health care desert with a scarcity of hospitals and resources. The prevalence of cerebrovascular disease and associated comorbidities are also some of the highest in the nation. Introduction: Ischemic stroke is a time-sensitive diagnosis. Prompt treatment in WV is difficult due to limited and isolated stroke-ready hospitals. Adoption of telestroke has helped to bypass these obstacles and improve access to care. Materials and Methods: Retrospective analyses; using data from the American Heart Association's Get With The Guidelines Stroke Data Registry, and other statewide agencies, we looked for trends in the volume of patients treated with intravenous-tissue plasminogen activator (tPA) in WV. We also reviewed data from West Virginia University's (WVU) telestroke database to assess trends in consult volumes and quality metrics. Results: Since the establishment of WVU telestroke, the total number of stroke patients receiving tPA across the state increased by 173% from 2015 (259 patients) to 2018 (448 patients) (p < 0.0001). Telestroke consults made up 24% (107/448) of total statewide tPA administrations for 2018. Between 2016 and 2018, the total symptomatic hemorrhage rate for tPA treated patients through telestroke was 1% (3/292). Telestroke also facilitated local care by avoiding patient transfer on average 65% of the time.Conclusion: Not only has telestroke increased the quantity of treated acute ischemic strokes, but it has also done so safely and effectively even in resource-poor areas. These findings demonstrate that telestroke is a useful tool for treating strokes, particularly those that happen far from stroke centers.

Hematopoietic effects of Azadirachta indica methanolic extract in cyclophosphamide mediated myelosuppressed albino rat.

Myelosuppression or bone marrow suppression is one of the most common side effects caused by anti-cancer drugs. Certain nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics and viruses like B19 virus can also cause bone marrow suppression resulting in serious consequences like leukopenia, anemia and thrombocytopenia. Currently, it is mainly treated by Filgrastim, use of which is not without side effects. Certain natural drugs can be a safer alternative to treat myelosuppression. Azadirachta indica, commonly known as Neem, is an important medicinal plant of subcontinent. Keeping in view the traditional uses of Neem, present study aims to investigate its potential role in reversing myelosuppression. Albino rats were used to determine hematopoietic activity of Neem leaves after inducing myelosuppression by cyclophosphamide given subcutaneously. Filgrastim was used as reference standard to compare the antimyelosuppressant activity of the drug. The drug was evaluated in three doses i.e. 50mg/kg, 100mg/kg and 200mg/kg body weight, while blood samples were drawn on 0, 1st, 7th, 14th and 21st day. The drug was found to be effective in reversing bone marrow suppression in all three doses based on the hematological parameters (mean WBC, RBC, platelets, Hb, Hct etc.) which improved significantly. The results suggest that the drug can be used as antimyelosuppressant after establishing its safety and identifying its active constituents with their mechanism of action.

Insight on the fractionations and structural characterizations of innovative antidiarrheal compounds screened from leaves of Psidium guajava of local origin in Pakistan.

Numerous ailments have been effectively treated with natural plants for long time all over the world. Plants provided a back bone for the exploration of novel medicinal compounds. Therefore, chief focus of our study was to isolate the biologically active compounds from the plant source and evaluate their antidiarrheal potentials, as diarrhea is still the most dominant disease in developing countries. The isolation and structure elucidation of two new compounds were identified from methanolic and chloroform extracts of Psidium guajava (guava) leaves. Extracts of plants were acquired by successive maceration from dried powder. Castor oil induced diarrheal-model was used to evaluate the antidiarrheal activity and therapeutic response was endorsed to the suppression of normal and wet stools in Spraug Dawley rats. Through the series of fractionations, compound-A was obtained from methanolic extract and named 3-(4-amino 1,3,8-tri-OH 5,6-di-CH3 7-propyl 1,2,3,4,4a,5,8,8a-octahydronaphthalen 2-yl) propanoic3-(4-NH3 7-butyl 1,3,8-tri-OH 5,6-di-CH3 1,2,3,4,4a,5,8,8a-octahydronaphthalen 2-yl)propanoic anhydride. Compound-B was entitled 5-(3-hydroxy-1,4-di-CH3-1,2,3,4,4a,5,8,8a-octahydronaphthalen-2-yl)pent-3-enoic acid was acquired from the chloroform extract. The structure elucidations of both compounds were interpreted through spectroscopic data, including EI-MS, FTIR, 1HNMR and 13C-NMR. The significant antidiarrheal activities were determined with crude extracts and isolated compounds. In inference, present study revealed that substantial antidiarrheal feature of guava is confined to the identified compounds.

Appraisal of organic extracts and isolated compounds of Azadirachta indica for in-vitro antioxidant, acetylcholinesterase and butyrylcholinesterase inhibitory activity.

The current study emphasized on assessment of Antioxidant, Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) inhibitory activity of the crude methanolic and chloroform leaves extracts along with their isolated compounds derived from Azadirachta indica. Phytochemical analysis revealed the manifestation of ancillary metabolites like alkaloid, anthraqinones, catechins, flavonoids, phenolic compounds, saponins, tannins and steroids. Methanolic crude extract of Azadirachta indica leaves revealed comparable antioxidant activity as that of quercetin and propyl gallate. As far as enzyme inhibitory activity was concerned, a significant AChE enzymes inhibition was observed. These findings confirm the traditional use of Azadirachticha indica as medicinal plant in the treatment of mental ailments and anti-inflammatory illnesses. Chloroform crude extract and isolated compounds showed weak antioxidant and enzyme inhibitory activities.

Anti myelosuppressant and hematopoietic activities of ethanolic fraction obtained from seeds of Carica papaya L.

Bone marrow suppression is one of the serious consequences of treatment with cytotoxic chemotherapeutic agents such as doxorubicin (DOX). It is very difficult to treat bone marrow suppression caused by anti-cancer drugs. This study was aimed to evaluate hematological effects particularly the antimyelosuppressant effects of ethanolic extract of papaya seeds at 200, 400 and 600 mg/kg daily dose for three weeks in doxorubicin induced hematopoietic suppression in rat model. Hematological parameters were assessed on weekly basis on days 0, 1, 7, 14 and 21. The alcoholic extract was found to cause remission of induced myelosuppression as indicated by a dose dependent increase in WBCs, neutrophils, lymphocytes, platelets, RBCs, Hb, hematocrit & mean corpuscular volume. However, the maximum dose (600mg/kg) of the extract showed maximum activity (p<0.05) in normalizing hematological parameters when compared with group B (induced group) and group A (controlled animals). These effects were compareable with those produced by Filgrastim 5µgm/kg used as standard or reference drug during these experiments. It is concluded from the results that papaya seeds possess myelostimulant activity and can be used to treat myelosuppression caused by chemotherapy. The drug can also be used for curing anemia, thrombocytopenia and immunological disorders characterized by myelosuppression.

Influence of levodropropizine and hydroxypropyl-ß-cyclodextrin association on the physicochemical characteristics of levodropropizine loaded in hydroxypropyl-ß-cyclodextrin microcontainers: Formulation and in vitro characterization.

BACKGROUND: Poorly water-soluble drugs do not dissolve well in aqueous-based gastrointestinal fluid; therefore, they are not well absorbed. Thus, employing a suitable solubility enhancing technique is necessary for such a drug. Drug/HP­ß­CD complexation is a promising way to improve solubility and dissolution of a poorly water-soluble drug. Levodropropizine was used as a model drug in this study. OBJECTIVES: The purpose of this research was to enhance the aqueous solubility and dissolution rate of levodropropizine by employing the inclusion complexation technique. MATERIAL AND METHODS: A microparticle formulation was prepared from levodropropizine and hydroxypropyl-ß-cyclodextrin (HP­ß­CD) in a 1:1 molar ratio through the spray-drying technique. The host-guest relationship between levodropropizine and HP­ß­CD was also investigated using the molecular docking computational methodology. The aqueous solubility and dissolution rate of levodropropizine in formulations were assessed and compared with those of the drug alone. X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR) were applied for the solid-state characterization of the prepared samples. RESULTS: According to the research outcomes, the levodropropizine/HP­ß­CD formulation had enhanced the aqueous solubility (351.12 ±13.26 vs 92.76 ±5.00 mg/mL) and dissolution rate (97.83 ±3.36 vs 3.12 ±1.76% in 10 min) of levodropropizine, compared to the plain drug powder. The levodropropizine/ HP­ß­CD formulation had converted the crystalline drug into its amorphous counterpart. Furthermore, no covalent interaction was found to exist between levodropropizine and HP­ß­CD. The spray-dried particles were discrete. Each particle had a shriveled appearance. CONCLUSIONS: The levodropropizine/HP­ß­CD formulation is, therefore, recommended for the more effective administration of levodropropizine through the oral route.