Topical Formulation For Stimulating Sweat Secretion as an Alternative to Iontophoresis

Sweat test or pilocarpine iontophoresis test is the existing method for diagnosis of cystic fibrosis that is recommended to perform at 48 hours after birth. However, the current method is painful, with several side effects such as full thickness skin burn, skin rash, erythema etc. Therefore, the purpose of this study is to develop a pilocarpine topical formulation which can stimulate sweat secretion when applied on skin without iontophoresis. Several formulations with Transcutol®, polyethylene glycol 400 (PEG 400), Polyethylene glycol 200 (PEG 200), menthol and salicylic acid (SA) each at varying concentrations were screened as penetration enhancers. In vitro penetration test (IVPT) was performed on these formulations to compare the influence of these ingredients on the penetration of pilocarpine. The results from the preliminary studies indicate that the formulation with SA shobetter penetration into porcine skin after both 10 minutes (120.29 ± 27.54 µg/cm2) and 40 minutes (158.97 ± 20.15 µg/cm2) compared to others. Based on the preliminary studies, the lead formulation was decided to have pilocarpine nitrate, ethanol and water as solvents, salicylic acid as penetration enhancer, PEG 200 as a hydrating agent to minimize any dehydration due to ethanol, menthol as a cooling agent and sodium hydroxide as a pH modifier. The penetration of pilocarpine nitrate on application of lead formulation into the porcine skin was compared to that of iontophoresis technique by both IVPT as well as tape stripping techniques. The IVPT results indicate that total amount of pilocarpine nitrate recovered from skin with passive formulation (152.04 ± 52.23 µg/cm2 after 10 min, 210.27 ± 53.72 µg/cm2 after 40 min) is higher than that of iontophoresis with pilocarpine solution (97.05 ± 27.93 µg/cm2 after 10 min, 140.56 ± 88.66 µg/cm2 after 40 min) at both 10 and 40 minutes. The tape stripping data shoa correlation with the IVPT results. The amount of pilocarpine recovered from the tape strips used in the lead formulation (78.46 µg/mg at 10 min and 53.32 µg/mg at 40 min) was significantly higher than the pilocarpine recovered from tape strips used for iontophoresis (13.32 µg/mg at 10 minute and 7.38 µg/mg at 40 minutes). The lead formulation was also investigated for its effectiveness by a clinical study on 20 human volunteers to determine if the developed formulation was efficient enough to stimulate the sweat production. The average amount of the sweat secreted due to passive formulation was found to be 77.28 ± 18.97 mg when applied on an area of 38.46 cm2. Based on these results, it can be concluded that the passive formulation was successful in delivering pilocarpine and to stimulate sweat secretion which can be a compliant alternative technique to iontophoresis

Distributed space scales in a semilinear reaction-diffusion system including a parabolic variational inequality: A well-posedness study

This paper treats the solvability of a semilinear reaction-diffusion system, which incorporates transport (diffusion) and reaction effects emerging from two separated spatial scales: $x$ - macro and $y$ - micro. The system's origin connects to the modeling of concrete corrosion in sewer concrete pipes. It consists of three partial differential equations which are mass-balances of concentrations, as well as, one ordinary differential equation tracking the damage-by-corrosion. The system is semilinear, partially dissipative, and coupled via the solid-water interface at the microstructure (pore) level. The structure of the model equations is obtained in \cite{tasnim1} by upscaling of the physical and chemical processes taking place within the microstructure of the concrete. Herein we ensure the positivity and $L^\infty-$bounds on concentrations, and then prove the global-in-time existence and uniqueness of a suitable class of positive and bounded solutions that are stable with respect to the two-scale data and model parameters. The main ingredient to prove existence include fixed-point arguments and convergent two-scale Galerkin approximations.Comment: 24 pages, 1 figur

Is adding charcoal to soil a good method for CO2 sequestration? - Modeling a spatially homogeneous soil

Carbon sequestration is the process of capture and long-term storage of atmospheric carbon dioxide (CO2) with the aim to avoid dangerous climate change. In this paper, we propose a simple mathematical model (a coupled system of nonlinear ODEs) to capture some of the dynamical effects produced by adding charcoal to fertile soils. The main goal is to understand to which extent charcoal is able to lock up carbon in soils. Our results are preliminary in the sense that we do not solve the CO2 sequestration problem. Instead, we do set up a flexible modeling framework in which the interaction between charcoal and soil can be tackled by means of mathematical tools. We show that our model is well-posed and has interesting large-time behaviour. Depending on the reference parameter range (e.g. type of soil) and chosen time scale, numerical simulations suggest that adding charcoal typically postpones the release of CO2

Association study of the angiotensin-converting enzyme (ACE) gene G2350A dimorphism with myocardial infarction

The angiotensin converting enzyme (ACE) is a strong candidate gene for myocardial infarction (MI). Insertion-deletion dimorphism in intron 16 of this gene has been inconclusively found to be associated with it. Several new polymorphisms in the ACE gene have been identified and among these, a dimorphism in exon 17, ACE G2350A, has a significant effect on plasma ACE concentrations. To assess the value of genotyping the ACE G2350A dimorphism in a genetically homogeneous population, we carried out a case-control study of dimorphism G2350A for a putative association with MI among Pakistani nationals. We investigated a sample population of 370 Pakistanis, comprising 163 controls, and 207 patients with clinical diagnosis of acute MI (AMI). ACE G2350A alleles were visualized by assays based on polymerase chain reaction and restriction endonuclease analysis. Frequencies of G alleles were 0.68 among controls and 0.72 among AMI patients. The ACE G2350A dimorphism showed no significant association with MI (chi2 = 0.90, 2 df, P = 0.64), plasma levels of homocysteine (P = 0.52) or with serum levels of folate (P = 0.299). The results indicate that ACE G2350A polymorphism is not associated with risk of myocardial infarction in the Pakistani population investigated here

Energy-Momentum Distribution: A Crucial Problem in General Relativity

This paper is aimed to elaborate the problem of energy-momentum in General Relativity. In this connection, we use the prescriptions of Einstein, Landau-Lifshitz, Papapetrou and M\"{o}ller to compute the energy-momentum densities for two exact solutions of Einstein field equations. The spacetimes under consideration are the non-null Einstein-Maxwell solutions and the singularity-free cosmological model. The electromagnetic generalization of the G\"{o}del solution and the G\"{o}del metric become special cases of the non-null Einstein-Maxwell solutions. It turns out that these prescriptions do not provide consistent results for any of these spacetimes. These inconsistence results verify the well-known proposal that the idea of localization does not follow the lines of pseudo-tensorial construction but instead follows from the energy-momentum tensor itself. These differences can also be understood with the help of the Hamiltonian approach.Comment: 28 pages, accepted for publication in Int. J. Mod. Phys.

Energy Distribution associated with Static Axisymmetric Solutions

This paper has been addressed to a very old but burning problem of energy in General Relativity. We evaluate energy and momentum densities for the static and axisymmetric solutions. This specializes to two metrics, i.e., Erez-Rosen and the gamma metrics, belonging to the Weyl class. We apply four well-known prescriptions of Einstein, Landau-Lifshitz, Papaterou and M$\ddot{o}$ller to compute energy-momentum density components. We obtain that these prescriptions do not provide similar energy density, however momentum becomes constant in each case. The results can be matched under particular boundary conditions.Comment: 18 pages, accepted for publication in Astrophysics and SpaceScienc

A persistent neutrophil-associated immune signature characterizes post-COVID-19 pulmonary sequelae

Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a concomitant increase in antiviral type I interferon signaling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Evaluation of these individuals at 12 months after recovery indicated that a subset of the individuals had not yet achieved full normalization of radiological and functional changes. These data provide insight into mechanisms driving development of pulmonary sequelae during and after COVID-19 and provide a rational basis for development of targeted approaches to prevent long-term complications

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.The Qatar Genome Program (QGP) and Qatar Biobank (QBB) are both Research and Development entities within Qatar Foundation for Education, Science and Community Development. The authors are thankful for everyone who contributed to this endeavor including the QGP and QBB team members, in addition to our partners at Hamad Medical Corporation (HMC), Sidra Medicine and other national stakeholders. The authors would like to especially thank all participants in this study for their continuous support