Hypoxia-mediated repression of pyruvate carboxylase drives immunosuppression.

BACKGROUND: Metabolic plasticity mediates breast cancer survival, growth, and immune evasion during metastasis. However, how tumor cell metabolism is influenced by and feeds back to regulate breast cancer progression are not fully understood. We identify hypoxia-mediated suppression of pyruvate carboxylase (PC), and subsequent induction of lactate production, as a metabolic regulator of immunosuppression. METHODS: We used qPCR, immunoblot, and reporter assays to characterize repression of PC in hypoxic primary tumors. Steady state metabolomics were used to identify changes in metabolite pools upon PC depletion. In vivo tumor growth and metastasis assays were used to evaluate the impact of PC manipulation and pharmacologic inhibition of lactate transporters. Immunohistochemistry, flow cytometry, and global gene expression analyzes of tumor tissue were employed to characterize the impact of PC depletion on tumor immunity. RESULTS: PC is essential for metastatic colonization of the lungs. In contrast, depletion of PC in tumor cells promotes primary tumor growth. This effect was only observed in immune competent animals, supporting the hypothesis that repression of PC can suppress anti-tumor immunity. Exploring key differences between the pulmonary and mammary environments, we demonstrate that hypoxia potently downregulated PC. In the absence of PC, tumor cells produce more lactate and undergo less oxidative phosphorylation. Inhibition of lactate metabolism was sufficient to restore T cell populations to PC-depleted mammary tumors. CONCLUSIONS: We present a dimorphic role for PC in primary mammary tumors vs. pulmonary metastases. These findings highlight a key contextual role for PC-directed lactate production as a metabolic nexus connecting hypoxia and antitumor immunity.

Remimazolam versus propofol for sedation in gastrointestinal endoscopy and colonoscopy within elderly patients: a meta-analysis of randomized controlled trials.

PURPOSE: Propofol has become the sedative of choice for endoscopy and colonoscopy. However, it has shown associations with various adverse effects, specifically in the geriatric population. In contrast, remimazolam is a novel benzodiazepine, demonstrating a superior clinical safety profile. Hence, this systematic review and meta-analysis aims to clarify the efficacy and safety of remimazolam versus propofol in elderly patients (≥ 60 years) undergoing gastrointestinal endoscopic and colonoscopy procedures. METHODS: Electronic databases including PubMed, Cochrane Library, ScienceDirect, and Google Scholar were explored from inception till January 7, 2024. The Cochrane Risk of Bias Tool for Randomized Controlled Trials (RoB-2) was utilized to evaluate the quality of each included study reported in this meta-analysis. RESULTS: Seven randomized control trials were included, resulting in the pooling of 1,466 patients (remimazolam: 731 patients; propofol: 735 patients). Propofol demonstrated a significantly lower time to loss of consciousness (P < 0.00001, 4 studies, 784 patients) and a greater sedation success after first dose (P = 0.05, 5 studies, 1,271 patients). Remimazolam reported a significantly lower risk of bradycardia (P = 0.02, 5 studies, 1,323 patients), hypoxemia (P < 0.00001, 6 studies, 1,389 patients), and pain on injection site (P < 0.00001, 5 studies, 1,184 patients). No statistically significant differences in sedation time, number of supplemental doses, procedural parameters, and other adverse outcomes were reported. CONCLUSION: As per the results of our analyses, propofol demonstrated comparatively superior efficacy, however, remimazolam demonstrated comparatively superior safety. The debatable evidence generated from this meta-analysis may not currently be powerful enough to advocate for the use of remimazolam in elderly patients undergoing gastrointestinal procedures; hence, further comprehensive studies are necessary in order to arrive at a robust conclusion.

Matching target color in polyolefins by estimating pigment concentrations using a four-flux model.

In applications of computer color formulation where color stimuli are optically thick (e.g., textiles, coatings, etc.), a simple single-constant or two-constant theory (e.g., Kubelka-Munk model) would suffice. To accurately predict reflectance and transmittance of materials with optical thickness ranging from optically thin to optically thick (e.g., plastics), mathematically complex radiative transfer theories (e.g., many-flux models) have been recommended. A many-flux model can even predict color formulation involving special-effect pigments (e.g., metallic, pearlescent, etc.), but implementation of such models is manyfold complicated. In the current study, applicability of a relatively simple Maheu-Letoulouzan-Gouesbet (MLG) four-flux radiative transfer model to optically varying pigmented polyolefins is thoroughly investigated. First, the MLG model was implemented to determine absorption and scattering coefficients of over 120 pigments where a new mean relative absolute spectral error (MRASE) between measured and calculated spectral reflectance and transmittance of the calibration samples was minimized as an objective function. Second, currently determined absorption and scattering coefficients were further validated by color recipe prediction of 350 historical product colors. Measured and predicted reflectance curves were compared in units of MRASE, CIEDE2000 color difference, metamerism index, root mean square error, and goodness-of-fit coefficient. Moreover, transmission matching was evaluated in units of percent difference between the required and predicted average transmittance. Results showed that with the current implementation of the MLG four-flux model, color recipes of at least 95% of the target colors can be predicted within the acceptability thresholds in units of different error metrics used in the study.

Acoustic scattering in lined panel cavities with membrane interfaces.

Noise control strategies are extremely important in industry. Acoustic liners and elastic membranes, which absorb or attenuate sound waves, are key components in ducting systems for active and passive noise reduction. In this article, we design and examine a reactive liner panel cavity with flexible interfaces. The lined panel cavity system is comprised of elastic membranes at the interfaces. The aim is to couple the incoming duct modes with the flexible components and then with the localized modes in the lined region. The governing equations for the lined panel cavity system are solved using a mode-matching technique that assures continuity of the normal velocities at the interfaces and can handle a range of strong coupling and higher-order edge conditions in contrast to the coupled mode theory. The aim is to investigate the effects of reactive liners and elastic membrane interfaces on wave scattering through the proposed acoustic enclosure design. The scattering performance of the proposed lined panel cavity is evaluated in terms of the reflected and transmitted energy flux as well as transmission loss. Analysis shows that the resonances at the membrane interfaces coupled to the linear cavities have a direct impact on power variations and the maximum transmission loss.

Fabrication of Ternary MoS2/CdS/Bi2S3-Based Nano Composites for Photocatalytic Dye Degradation.

The synthesis and design of low-cost visible-light-active catalysts for the photodegradation of organic dyes have been regarded as an efficient way to use solar energy in addressing environmental issues. We report the fabrication of MoS2/CdS nanoparticles functionalized with Bi2S3 nanoflakes. The ternary composites of "MoS2/CdS/Bi2S3" were synthesized in situ by a hydrothermal method at different temperatures. The changes in structural, optical, and morphological properties of the synthesized CdS/MoS2/Bi2S3 were explored. The effects of Bi2S3 on CdS/MoS2 were thoroughly studied by performing an X-ray diffractometer (XRD), a scanning electron microscope (SEM), an ultra-violet-visible spectrometer (Uv-vis), and Fourier transform infrared spectroscopic (FT-IR) studies of the nanoparticles. XRD confirms the cubical crystal structure of the nanoparticles. SEM studies possess the modulation in the surface morphology with the tenability in volume ratios of "MoS2/CdS/Bi2S3" composites. It was observed that the bandgaps calculated using absorption measurements could be manipulated from 2.40 eV to 0.97 eV with varying Bi2S3 in the MoS2/CdS nanostructures. FT-IR confirmed the synthesis of "MoS2/CdS/Bi2S3" nanoparticles. On allowing the visible light to fall for 120 min, it was observed that "MoS2/CdS/Bi2S3" degrades the methylene blue up to 90%. The calculated results of "MoS2/CdS/Bi2S3" suggest that the synthesized material could be a strong candidate for photodegradation applications. This research work explains the synthesis of MoS2/CdS/Bi2S3-based nanocomposites for the degradation of dye using a photocatalytic process. The final results show that this catalyst effectively degrades the dye.

Bombax ceiba flower extract mediated synthesis of Se nanoparticles for antibacterial activity and urea detection.

Plant mediated synthesis of metallic nanomaterials has emerged as a non-toxic and economical approach to their applications in diverse fields especially in biomedical sciences. Herein, this study first time reporting the use of Bombax ceiba flower extract for synthesis of selenium nanoparticles (SeNPs). Initially, SeNPs were confirmed by turning the color of reaction mixtures from light yellow to brick-red. Scanning electron microscope (SEM) and Transmission electron microscopy (TEM) images showed spherical shaped nanoparticles with smooth surface, size ranges between 30 and 150 nm. Dynamic light scattering (DLS) showed 100-150 nm for the distribution of particle size. X-ray diffraction (XRD) analysis revealed SeNPs crystallinity and confirmed by matching with selenium JCPD card No. 06-362. Energy-dispersive X-ray (EDX) spectra showed presence of pure Se peaks that corroborate the conversion of selenium ions into its elemental form by bio-reduction. Fourier-transform infrared spectroscopy (FTIR) spectra demonstrated that involvement of -OH, C-H, C=C, and C=O functional groups for SeNPs formation. Raman Spectra peaks at 250 cm-1 represent asymmetric trigonal selenium (t-Se). Ultraviolet-visible spectrophotometer (UV-Vis) peaks at 296 and 306 nm which is an indication of surface plasmon resonance (SPR). Moreover, maximum antibacterial activity of SeNPs were observed against Staphylococcus aureus- a gram positive bacteria that possess zone of inhibition (ZOI) 20 mm and Klebsiella pneumonia and Pseudomonas aeruginosa-gram negative bacteria with ZOI 28 mm, respectively, at concentration 100 µg/ml. In addition, the surface functionalities induced through extract components adhere over Se binds with urea and give its detection up to 1mM in milk sample. Conclusively, synthesized SeNPs may function as a potential antibacterial pharmaceutical candidate.

The Role of Religion and Spirituality to Cope with COVID-19 Infections Among People of Lower Socioeconomic Status in Pakistan: An Exploratory Qualitative Study.

Religion and spirituality have been key coping mechanisms of Pakistani Muslims amidst natural calamities such as the COVID-19 pandemic. This study aimed to identify and explore the role of religion and spirituality in the recovery of COVID-19 patients in lower socioeconomics. The data for this qualitative research study were collected from 13 people in Pakistan who survived COVID-19 infection during the wave of the Omicron variant. The participants of this study referenced four key themes about their story of getting infected by COVID-19 and recovering from it and referenced religion and spirituality as an overarching aspect of that story. The patients who recovered believed that COVID-19 was a punishment from God for sinful humanity, which was unavoidable. Amidst such a belief, the studied patients tried to avoid hospitalization but prayed to God for mercy, forgiveness, and help in their recovery. A few who took medical treatment also established and/or strengthened their spiritual connections seeking quick recovery from the infection. The participants of this study believed that their religion or spirituality played a medicinal role in their recovery from COVID-19 infection.

Between Life and Death: How do Muslim Terminal Patients in Pakistan cope with Hepatitis C utilizing their Beliefs and Social Support?

Life-threatening events including terminal illness intensify the search for meaning and incite individuals to get closer to religion. Terminal patients can often find religious practices as helpful as medical therapy for bettering both physical and mental health. The present research aims to explain the interaction between religion, spirituality, and social support in coping with terminal illness among Muslim hepatitis C patients in Pakistan. A semi-structured open-ended interview guide was utilized to collect the data. Participants expressed that the deployment of religious and spiritual beliefs along with socio-emotional support during illness fostered medical therapy. Participants also revealed that belief in God provided them the strength to be steadfast during the terminal stage of the disease. Religious beliefs enabled terminal participants to accept death as an eventual reality and a normal part of their lives. Furthermore, participants put forward their longing for those kinds of religious practices that terminal diseases usually restrained them from receiving. The emotional support stemming from social relationships also improved resilience to cope with the terminal stage of illness. The study concludes that the interplay of religion, spirituality, and social support normalizes the fear of death, lessens pain, and improves resilience among Muslim hepatitis C patients in Pakistan.

Progress Toward Poliomyelitis Eradication - Pakistan, January 2021-July 2022.

After reporting a single wild poliovirus (WPV) type 1 (WPV1) case in 2021, Pakistan reported 14 cases during April 1-July 31, 2022. Pakistan and Afghanistan are the only countries where endemic WPV transmission has never been interrupted (1). In its current 5-year strategic plan, the Global Polio Eradication Initiative (GPEI) has set a goal of interrupting all WPV1 transmission by the end of 2023 (1-3). The reemergence of WPV cases in Pakistan after 14 months with no case detection has uncovered transmission in southern Khyber Pakhtunkhwa province, the most historically challenging area. This report describes Pakistan's progress toward polio eradication during January 2021-July 2022 and updates previous reports (4,5). As of August 20, 2022, all but one of the 14 WPV1 cases in Pakistan during 2022 have been reported from North Waziristan district in Khyber Pakhtunkhwa. In underimmunized populations, excretion of vaccine virus can, during a period of 12-18 months, lead to reversion to neurovirulence, resulting in circulating vaccine-derived polioviruses (cVDPVs), which can cause paralysis and outbreaks. An outbreak of cVDPV type 2 (cVDPV2), which began in Pakistan in 2019, has been successfully contained; the last case occurred in April 2021 (1,6). Despite program improvements, 400,000-500,000 children continue to be missed during nationwide polio supplementary immunization activities (SIAs),* and recent isolation of poliovirus from sewage samples collected in other provinces suggests wider WPV1 circulation during the ongoing high transmission season. Although vaccination efforts have been recently complicated by months of flooding during the summer of 2022, to successfully interrupt WPV1 transmission in the core reservoirs in southern Khyber Pakhtunkhwa and reach the GPEI goal, emphasis should be placed on further improving microplanning and supervision of SIAs and on systematic tracking and vaccination of persistently missed children in these reservoir areas of Pakistan.

Toward non-metameric reflectance recovery by emulating the spectral neighborhood using corresponding color information.

In learning-based reflectance reconstruction methods, usually localized training samples are used to reconstruct spectral curves. The state-of-the-art methods localize the training samples based on their colorimetric color differences with the test sample. This approach is dependent on the working color space, color difference equation, and/or illuminant used, and it may result in a metameric match. This issue can be resolved by localizing the training samples based on their spectral difference with the test sample; however, this would require an already unknown spectral curve of the test sample. In this paper, use of corresponding color information to emulate the spectral neighborhood of the test color for non-metameric reflectance recovery is proposed. The Wiener estimation method was extended by (1) using two thresholds, (i) on the color difference between the test sample and the training samples under the reference illuminant and (ii) on the color difference between the corresponding color of the test sample and the training samples under another illuminant, to mimic the spectral neighborhood of the test sample within the gamut of the training data, and (2) also using the tristimulus values of the corresponding color in the regression. Results showed that the proposed extension of the Wiener estimation method improved the reflectance recovery and hence reduced the metamerism.

A Denoising and Fourier Transformation-Based Spectrograms in ECG Classification Using Convolutional Neural Network.

The non-invasive electrocardiogram (ECG) signals are useful in heart condition assessment and are found helpful in diagnosing cardiac diseases. However, traditional ways, i.e., a medical consultation required effort, knowledge, and time to interpret the ECG signals due to the large amount of data and complexity. Neural networks have been shown to be efficient recently in interpreting the biomedical signals including ECG and EEG. The novelty of the proposed work is using spectrograms instead of raw signals. Spectrograms could be easily reduced by eliminating frequencies with no ECG information. Moreover, spectrogram calculation is time-efficient through short-time Fourier transformation (STFT) which allowed to present reduced data with well-distinguishable form to convolutional neural network (CNN). The data reduction was performed through frequency filtration by taking a specific cutoff value. These steps makes architecture of the CNN model simple which showed high accuracy. The proposed approach reduced memory usage and computational power through not using complex CNN models. A large publicly available PTB-XL dataset was utilized, and two datasets were prepared, i.e., spectrograms and raw signals for binary classification. The highest accuracy of 99.06% was achieved by the proposed approach, which reflects spectrograms are better than the raw signals for ECG classification. Further, up- and down-sampling of the signals were also performed at various sampling rates and accuracies were attained.

Religious construction and interpretation of pain: Lived experiences of terminally ill hepatitis C Muslim patients.

Pain is a complex, multidimensional phenomenon and integral component of illness but little is known about its religious construction and interpretation. This article discusses an important yet neglected component of terminal illness which is the religious construction of pain. Eleven hepatitis C Muslim patients admitted to the liver center were recruited for this study. In-depth interviews helped the identification of dominant themes. The study found that terminal patients construct pain in a religious context and interpret it into religious realms. For them, pain helps to realize their debility and helplessness. They think pain has a transformatory potential and can help them turn to be very strong and brave. The participants also reported having a belief that pain in this world could be compensated in the life hereafter and they will be rewarded with good deeds and bestowed with the Jannah (paradise). The terminal patients strongly influenced by religion and spirituality believed to be experiencing pain as a punishment of their misdeeds. Thus, pain was helping them to normalize their end-of-life experiences and ease the terminal stage of their illness.

Physical activity in Pakistani perspective: issues, implications, and recommendations.

It has been established that the benefits of physical activity on physical, psychological and social aspects of humans are substantially correlated with cardiovascular disorders, obesity, cancer, social anxieties and depressions, and enhanced socio-economic profile. In children and adolescents, physical activity has been correlated with academic achievements, social harmony and mental health. Similarly, in adults/old people, physical activity has been of variable benefits, bringing the chances of prolonged healthier lives. Though substantial work has been reported globally, there still is a paucity of literature in Pakistan regarding various aspects of physical activity. The current narrative review was planned to summarise the research work conducted in, or has emanated from, Pakistan in teens/college/school and university students, and adults from Pakistan on associated aspects of physical activity, its present scenario, pitfalls, future horizons, and to ultimately deduce gaps in research areas which can be taken up for the directional approach to enhance physical activity within the Pakistani community.

SNPs at 3'UTR of APOL1 and miR-6741-3p target sites associated with kidney diseases more susceptible to SARS-COV-2 infection: in silco and in vitro studies.

Acute Kidney Injury (AKI) is a common manifestation of COVID-19 and several cases have been reported in the setting of the high-risk APOL1 genotype (common genetic variants). This increases the likelihood that African American people with the high-risk genotype APOL1 are at increased risk for kidney disease in the COVID-19 environment. Single-nucleotide polymorphisms (SNPs) are found in various microRNAs (miRNAs) and target genes change the miRNA activity that leads to different diseases. Evidence has shown that SNPs increase/decrease the effectiveness of the interaction between miRNAs and disease-related target genes. The aim of this study is not only to identify miRSNPs on the APOL1 gene and SNPs in miRNA genes targeting 3'UTR but also to evaluate the effect of these gene variations in kidney patients and their association with SARS-COV-2 infection. In 3'UTR of the APOL1 gene, we detected 96 miRNA binding sites and 35 different SNPs with 10 different online software in the binding sites of the miRNA (in silico). Also we studied gene expression of patients and control samples by using qRT-PCR (in vitro). In silico study, the binding site of miR-6741-3p on APOL1 has two SNPs (rs1288875001, G > C; rs1452517383, A > C) on APOL1 3'UTR, and its genomic sequence is the same nucleotide as rs1288875001. Similarly, two other SNPs (rs1142591, T > A; rs376326225, G > A) were identified in the binding sites of miR-6741-3p at the first position. Here, the miRSNP (rs1288875001) in APOL1 3'UTR and SNP (rs376326225) in the miR-6741-3p genomic sequence are cross-matched in the same binding region. In vitro study, the relative expression levels were calculated by the 2-ΔΔCt method & Mann-Whitney U test. The expression of APOL1 gene was different in chronic kidney patients along with COVID-19. By these results, APOL1 expression was found lower in patients than healthy (p < 0.05) in kidney patients along with COVID-19. In addition, miR-6741-3p targets many APOL1-related genes (TLR7, SLC6A19, IL-6,10,18, chemokine (C-C motif) ligand 5, SWT1, NFYB, BRF1, HES2, NFYB, MED12L, MAFG, GTF2H5, TRAF3, angiotensin II receptor-associated protein, PRSS23) by evaluating online software in the binding sites of the miR-6741-3p. miR-6741-3p has not previously shown any association with kidney diseases and SARS-COV-2 infection. It assures that APOL1 can have a significant consequence in kidney-associated diseases by different pathways. Henceforth, this study represents and demonstrates an effective association between miR-6741-3p and kidney diseases, i.e., collapsing glomerulopathy, chronic kidney disease (CKD), acute kidney injury (AKI), and tubulointerstitial lesions susceptibility to SARS-COV-2 infection via in silico and in vitro exploration and recommended to have better insight.

Photosynthesis research under climate change.

Increasing global population and climate change uncertainties have compelled increased photosynthetic efficiency and yields to ensure food security over the coming decades. Potentially, genetic manipulation and minimization of carbon or energy losses can be ideal to boost photosynthetic efficiency or crop productivity. Despite significant efforts, limited success has been achieved. There is a need for thorough improvement in key photosynthetic limiting factors, such as stomatal conductance, mesophyll conductance, biochemical capacity combined with Rubisco, the Calvin-Benson cycle, thylakoid membrane electron transport, nonphotochemical quenching, and carbon metabolism or fixation pathways. In addition, the mechanistic basis for the enhancement in photosynthetic adaptation to environmental variables such as light intensity, temperature and elevated CO2 requires further investigation. This review sheds light on strategies to improve plant photosynthesis by targeting these intrinsic photosynthetic limitations and external environmental factors.

ZCAM, a colour appearance model based on a high dynamic range uniform colour space.

A colour appearance model based on a uniform colour space is proposed. The proposed colour appearance model, ZCAM, comprises of comparatively simple mathematical equations, and plausibly agrees with the psychophysical phenomenon of colour appearance perception. ZCAM consists of ten colour appearance attributes including brightness, lightness, colourfulness, chroma, hue angle, hue composition, saturation, vividness, blackness, and whiteness. Despite its relatively simpler mathematical structure, ZCAM performed at least similar to the CIE standard colour appearance model CIECAM02 and its revision, CAM16, in predicting a range of reliable experimental data.

HantavirusesDB: Vaccinomics and RNA-based therapeutics database for the potentially emerging human respiratory pandemic agents.

Hantaviruses are etiological agents of several severe respiratory illnesses in humans and their human-to-human transmission has been reported. To cope with any potential pandemic, this group of viruses needs further research and a data platform. Therefore, herein we developed a database "HantavirusesDB (HVdb)", where genomics, proteomics, immune resource, RNAi based therapeutics and information on the 3D structures of druggable targets of the Orthohantaviruses are provided on a single platform. The database allows the researchers to effectively map the therapeutic strategies by designing multi-epitopes subunit vaccine and RNA based therapeutics. Moreover, the ease of the web interface allow the users to retrieve specific information from the database. Because of the high quality and excellent functionality of the HVdb, therapeutic research of Hantaviruses can be accelerated, and data analysis might be a foundation to design better treatment strategies targeting the hantaviruses. The database is accessible at http://hvdb.dqweilab-sjtu.com/index.php.

Rational Development of Guanidinate and Amidinate Based Cerium and Ytterbium Complexes as Atomic Layer Deposition Precursors: Synthesis, Modeling, and Application.

Owing to the limited availability of suitable precursors for vapor phase deposition of rare-earth containing thin-film materials, new or improved precursors are sought after. In this study, we explored new precursors for atomic layer deposition (ALD) of cerium (Ce) and ytterbium (Yb) containing thin films. A series of homoleptic tris-guanidinate and tris-amidinate complexes of cerium (Ce) and ytterbium (Yb) were synthesized and thoroughly characterized. The C-substituents on the N-C-N backbone (Me, NMe2 , NEt2 , where Me=methyl, Et=ethyl) and the N-substituents from symmetrical iso-propyl (iPr) to asymmetrical tertiary-butyl (tBu) and Et were systematically varied to study the influence of the substituents on the physicochemical properties of the resulting compounds. Single crystal structures of [Ce(dpdmg)3 ] 1 and [Yb(dpdmg)3 ] 6 (dpdmg=N,N'-diisopropyl-2-dimethylamido-guanidinate) highlight a monomeric nature in the solid-state with a distorted trigonal prismatic geometry. The thermogravimetric analysis shows that the complexes are volatile and emphasize that increasing asymmetry in the complexes lowers their melting points while reducing their thermal stability. Density functional theory (DFT) was used to study the reactivity of amidinates and guanidinates of Ce and Yb complexes towards oxygen (O2 ) and water (H2 O). Signified by the DFT calculations, the guanidinates show an increased reactivity toward water compared to the amidinate complexes. Furthermore, the Ce complexes are more reactive compared to the Yb complexes, indicating even a reactivity towards oxygen potentially exploitable for ALD purposes. As a representative precursor, the highly reactive [Ce(dpdmg)3 ] 1 was used for proof-of-principle ALD depositions of CeO2 thin films using water as co-reactant. The self-limited ALD growth process could be confirmed at 160 °C with polycrystalline cubic CeO2 films formed on Si(100) substrates. This study confirms that moving towards nitrogen-coordinated rare-earth complexes bearing the guanidinate and amidinate ligands can indeed be very appealing in terms of new precursors for ALD of rare earth based materials.

Microemulsified Gel Formulations for Topical Delivery of Clotrimazole: Structural and In Vitro Evaluation.

Microemulsified gels (µEGs) with fascinating functions have become indispensable as topical drug delivery systems due to their structural flexibility, high stability, and facile manufacturing process. Topical administration is an attractive alternative to traditional methods because of advantages such as noninvasive administration, bypassing first-pass metabolism, and improving patient compliance. In this article, we report on the new formulations of microemulsion-based gels suitable for topical pharmaceutical applications using biocompatible and ecological ingredients. For this, two biocompatible µE formulations comprising clove oil/Brij-35/water/ethanol (formulation A) and clove oil/Brij-35/water/1-propanol (formulation B) were developed to encapsulate and improve the load of an antimycotic drug, Clotrimazole (CTZ), and further gelatinized to control the release of CTZ through skin barriers. By delimiting the pseudo-ternary phase diagram, optimum µE formulations with clove oil (∼15%) and Brij-35 (∼30%) were developed, keeping constant surfactant/co-surfactant ratio (1:1), to upheld 2.0 wt % CTZ. The as-developed formulations were further converted into smart gels by adding 2.0 wt % carboxymethyl cellulose (CMC) as a cross-linker to adhere to the controlled release of CTZ through complex skin barriers. Electron micrographs show a fine, monodispersed collection of CTZ-µE nanodroplets (∼60 nm), which did not coalesce even after gelation, forming spherical CTZ-µEG (∼90 nm). However, the maturity of CTZ nanodroplets observed by dynamic light scattering suggests the affinity of CTZ for the nonpolar microenvironment, which was further supported by the peak-to-peak correlation of Fourier transform infrared (FTIR) analysis and fluorescence measurement. In addition, HPLC analysis showed that the in vitro permeation release of CTZ-µEG from rabbit skin in the ethanolic phosphate buffer (pH = 7.4) was significantly increased by >98% within 6.0 h. This indicates the sustained release of CTZ in µEBG and the improvement in transdermal therapeutic efficacy of CTZ over its traditional topical formulations.

Progress Toward Poliomyelitis Eradication - Pakistan, January 2020-July 2021.

When the Global Polio Eradication Initiative began in 1988, wild poliovirus (WPV) transmission was occurring in 125 countries; currently, only WPV type 1 (WPV1) transmission continues, and as of August 2021, WPV1 transmission persists in only two countries (1,2). This report describes Pakistan's progress toward polio eradication during January 2020-July 2021 and updates previous reports (3,4). In 2020, Pakistan reported 84 WPV1 cases, a 43% reduction from 2019; as of August 25, 2021, Pakistan has reported one WPV1 case in 2021. Circulating vaccine-derived poliovirus (cVDPV) emerges as a result of attenuated oral poliovirus vaccine (OPV) virus regaining neurovirulence after prolonged circulation in underimmunized populations and can lead to paralysis. In 2019, 22 cases of cVDPV type 2 (cVDPV2) were reported in Pakistan, 135 cases were reported in 2020, and eight cases have been reported as of August 25, 2021. Because of the COVID-19 pandemic, planned supplementary immunization activities (SIAs)* were suspended during mid-March-June 2020 (3,5). Seven SIAs were implemented during July 2020-July 2021 without substantial decreases in SIA quality. Improving the quality of polio SIAs, vaccinating immigrants from Afghanistan, and implementing changes to enhance program accountability and performance would help the Pakistan polio program achieve its goal of interrupting WPV1 transmission by the end of 2022.