Generation of Eroded Nanoplastics from Domestic Wastes and Their Impact on Macrophage Cell Viability and Gene Expression.

This study reports an innovative approach for producing nanoplastics (NP) from various types of domestic waste plastics without the use of chemicals. The plastic materials used included water bottles, styrofoam plates, milk bottles, centrifuge tubes, to-go food boxes, and plastic bags, comprising polyethylene terephthalate (PET), polystyrene (PS), polypropylene (PP), high-density polyethylene (HDPE), and Poly (Ethylene-co-Methacrylic Acid) (PEMA). The chemical composition of these plastics was confirmed using Raman and FTIR spectroscopy, and they were found to have irregular shapes. The resulting NP particles ranged from 50 to 400 nm in size and demonstrated relative stability when suspended in water. To assess their impact, the study investigated the effects of these NP particulates on cell viability and the expression of genes involved in inflammation and oxidative stress using a macrophage cell line. The findings revealed that all types of NP reduced cell viability in a concentration-dependent manner. Notably, PS, HDPE, and PP induced significant reductions in cell viability at lower concentrations, compared to PEMA and PET. Moreover, exposure to NP led to differential alterations in the expression of inflammatory genes in the macrophage cell line. Overall, this study presents a viable method for producing NP from waste materials that closely resemble real-world NP. Furthermore, the toxicity studies demonstrated distinct cellular responses based on the composition of the NP, shedding light on the potential environmental and health impacts of these particles.

Efficacy of recombinant enolase as a candidate vaccine against Haemaphysalis longicornis tick infestation in mice.

Tick infestation causes a significant threat to human and animal health, requiring effective immunological control methods. This study aimed to investigate the potential of recombinant Haemaphysalis longicornis enolase protein for tick vaccine development. The exact mechanism of the recently identified enolase protein from the H. longicornis Jeju strain remains poorly understood. Enolase plays a crucial role in glycolysis, the metabolic process that converts glucose into energy, and is essential for the motility, adhesion, invasion, growth, and differentiation of ticks. In this study, mice were immunized with recombinant enolase, and polyclonal antibodies were generated. Western blot analysis confirmed the specific recognition of enolase by the antiserum. The effects of immunization on tick feeding and attachment were assessed. Adult ticks attached to the recombinant enolase-immunized mice demonstrated longer attachment time, increased blood-sucking abilities, and lower engorgement weight than the controls. The nymphs and larvae had a reduced attachment rate and low engorgement rate compared to the controls. Mice immunized with recombinant enolase expressed in Escherichia coli displayed 90% efficacy in preventing tick infestation. The glycolytic nature of enolase and its involvement in crucial physiological processes makes it an attractive target for disrupting tick survival and disease transmission. Polyclonal antibodies recognize enolase and significantly reduce attachment rates, tick feeding, and engorgement. Our findings indicate that recombinant enolase may be a valuable vaccine candidate for H. longicornis infection in experimental murine model.

Effects of histamine and antihistamine on the hard tick Haemaphysalis longicornis during blood sucking.

At the time of host attachment, ticks are very sensitive to histamine, but during rapid blood sucking they paradoxically require histamine. Using a rabbit model, we studied the effects of histamine and antihistamine during attachment and fast-feeding in different life stages of Haemaphysalis longicorns. We examined how they responded to histamine and antihistamine by analyzing the detachment rate, histology of feeding lesions, and post-feeding behavior. A significant difference (P<0.01) was found in the detachment rate between experimental and control treatments throughout the observation period. Ticks exhibited a higher detachment rate (30.1%) at 12 h after histamine application during attachment time and on antihistamine-treated skin (25.4%) at 96 h during fast-feeding. After feeding on histamine-treated rabbits, the fully engorged body weights of larvae and nymphs were 0.7±0.36 mg and 3.5±0.65 mg, respectively. An average increase in body weight of 0.6±0.05 mg and 3.2±0.30 mg was observed for larvae and nymphs compared to the respective control weights. Nymphs and adults engorged after antihistamine treatment had an average body weight of 1.3±0.54 mg and 54±0.81 mg, respectively. An average decrease in body weight was observed in antihistamine-treated H. longicornis compared with control nymphs (3.3±0.42 mg) and adults (174±1.78 mg). Skin biopsies were collected after treatment, and differential histopathological characteristics were found between the treatment and control groups. Tick-infested skin collected from rabbits in the antihistamine-treated group lacked erythrocytes in the feeding pool, indicating that antihistamine impaired tick fast-feeding stage.

Synthesis of Microwave Functionalized, Nanostructured Polylactic Co-Glycolic Acid (nfPLGA) for Incorporation into Hydrophobic Dexamethasone to Enhance Dissolution.

The low solubility and slow dissolution of hydrophobic drugs is a major challenge for the pharmaceutical industry. In this paper, we present the synthesis of surface-functionalized poly(lactic-co-glycolic acid) (PLGA) nanoparticles for incorporation into corticosteroid dexamethasone to improve its in vitro dissolution profile. The PLGA crystals were mixed with a strong acid mixture, and their microwave-assisted reaction led to a high degree of oxidation. The resulting nanostructured, functionalized PLGA (nfPLGA), was quite water-dispersible compared to the original PLGA, which was non-dispersible. SEM-EDS analysis showed 53% surface oxygen concentration in the nfPLGA compared to the original PLGA, which had only 25%. The nfPLGA was incorporated into dexamethasone (DXM) crystals via antisolvent precipitation. Based on SEM, RAMAN, XRD, TGA and DSC measurements, the nfPLGA-incorporated composites retained their original crystal structures and polymorphs. The solubility of DXM after nfPLGA incorporation (DXM-nfPLGA) increased from 6.21 mg/L to as high as 87.1 mg/L and formed a relatively stable suspension with a zeta potential of -44.3 mV. Octanol-water partitioning also showed a similar trend as the logP reduced from 1.96 for pure DXM to 0.24 for DXM-nfPLGA. In vitro dissolution testing showed 14.0 times higher aqueous dissolution of DXM-nfPLGA compared to pure DXM. The time for 50% (T50) and 80% (T80) of gastro medium dissolution decreased significantly for the nfPLGA composites; T50 reduced from 57.0 to 18.0 min and T80 reduced from unachievable to 35.0 min. Overall, the PLGA, which is an FDA-approved, bioabsorbable polymer, can be used to enhance the dissolution of hydrophobic pharmaceuticals and this can lead to higher efficacy and lower required dosage.

Microwave Synthesis of Nanostructured Functionalized Polylactic Acid (nfPLA) for Incorporation Into a Drug Crystals to Enhance Their Dissolution.

Active pharmaceutical ingredients that have low aqueous solubility pose a challenge in the field of drug delivery. In this paper we report for the first time the synthesis of nano-structured, hydrophilized polylactic acid (nfPLA) and its application in the delivery of low solubility drugs. Microwave induced acid oxidation was used to generate nfPLA where the oxygen concentration increased from 27.0 percent to 41.0 percent. Also, the original non dispersible PLA was converted to a relatively dispersible form with an average particle size of 131.4 nm and a zeta potential of -23.3 mV. Small quantities of the nfPLA were incorporated into the crystals (0.5 to 2.0 % by weight) of a highly hydrophobic, low solubility antifungal drug Griseofulvin (GF) to form a composite (GF-nfPLA). An antisolvent approach was used for the synthesis of the drug composite. SEM and Raman imaging showed non-uniform distribution of the nfPLA on the crystal surface. The solubility of GF increased from 8.89 µg/mL to as high as 49.67 µg/mL for the GF-nfPLA. At the same time zeta potential changed from -15.4 mV to -39.0 mV, therefore the latter was a relatively stable colloid. Octanol-water partitioning also showed a similar effect as logP reduced from 2.16 for pure GF to 0.55 for GF-nfPLA. In vitro dissolution testing showed six times higher aqueous solubility of GF-nfPLA compared to pure GF. The time for 50 (T50) and 80 % (T80) dissolution reduced significantly for the nfPLA composites; T50 reduced from 40.0 to 14.0 min and T80 reduced form unachievable to 47.0 min. Overall, the PLA which is an FDA approved, bioabsorbable polymer can be used to enhance the dissolution of hydrophobic pharmaceuticals and this can lead to higher efficacy and lower the required dosage for drugs.

Seroprevalence of Anti-SARS-CoV-2 Antibodies in Chattogram Metropolitan Area, Bangladesh.

Seroprevalence studies of COVID-19 are used to assess the degree of undetected transmission in the community and different groups such as health care workers (HCWs) are deemed vulnerable due to their workplace hazards. The present study estimated the seroprevalence and quantified the titer of anti-SARS-CoV-2 antibody (IgG) and its association with different factors. This cross-sectional study observed HCWs, in indoor and outdoor patients (non-COVID-19) and garment workers in the Chattogram metropolitan area (CMA, N = 748) from six hospitals and two garment factories. Qualitative and quantitative ELISA were used to identify and quantify antibodies (IgG) in the serum samples. Descriptive, univariable, and multivariable statistical analysis were performed. Overall seroprevalence and among HCWs, in indoor and outdoor patients, and garment workers were 66.99% (95% CI: 63.40-70.40%), 68.99% (95% CI: 63.8-73.7%), 81.37% (95% CI: 74.7-86.7%), and 50.56% (95% CI: 43.5-57.5%), respectively. Seroprevalence and mean titer was 44.47% (95% CI: 38.6-50.4%) and 53.71 DU/mL in the non-vaccinated population, respectively, while it was higher in the population who received a first dose (61.66%, 95% CI: 54.8-68.0%, 159.08 DU/mL) and both doses (100%, 95% CI: 98.4-100%, 255.46 DU/mL). This study emphasizes the role of vaccine in antibody production; the second dose of vaccine significantly increased the seroprevalence and titer and both were low in natural infection.

Enhanced aqueous dissolution of hydrophobic apixaban via direct incorporation of hydrophilic nanographene oxide.

In this study, we have directly incorporated nanographene oxide (nGO) into a hydrophobic drug for enhanced dissolution performance through an antisolvent technique. Apixaban (APX) drug composites were synthesized with nGO incorporation ranging from 0.8% to 2.0% concentration. It was observed that the nGO was successfully embedded without any changes to the original drug crystal structure or physical properties. Dissolution of the drug composites was evaluated using US Pharmacopeia Paddle Method (USP 42). The time needed to reach a 50% release (T50) reduced from 106 min to 24 min with the integration of 1.96% nGO in APX and the T80 also dropped accordingly. Alternatively, dissolution rate showed promising performance with increase in nGO concentration. Initial dissolution rate increased dramatically from 74 µg/min to 540 µg/min. Further, work done in intestinal media revealed T50 went from not dissolving to 79.0 min. Decreased lipophilicity or logP value and increased aqueous solubility are both accredited to hydrophilic nGO water dispersion, producing a hydrophilic channel into the drug crystal surfaces through intermolecular interaction. Additionally, physical, and chemical characterizations confirm that hydrophobic apixaban was successfully transformed into a hydrophilic composite, showing potential for this technology to improve dissolution rate of a model hydrophobic compound.

Hydrophilic and Functionalized Nanographene Oxide Incorporated Faster Dissolving Megestrol Acetate.

The aim of this work is to present an approach to enhance the dissolution of progestin medication, megestrol acetate (also known as MEGACE), for improving the dissolution rate and kinetic solubility by incorporating nano graphene oxide (nGO). An antisolvent precipitation process was investigated for nGO-drug composite preparation, where prepared composites showed crystalline properties that were similar to the pure drug but enhanced aqueous dispersibility and colloidal stability. To validate the efficient release profile of composite, in vitro dissolution testing was carried out using United States Pharmacopeia, USP-42 paddle method, with gastric pH (1.4) and intestinal pH (6.5) solutions to mimic in vivo conditions. Pure MA is practically insoluble (2 µg/mL at 37 °C). With the incorporation of nGO, it was possible to dissolve nearly 100% in the assay. With the incorporation of 1.0% of nGO, the time required to dissolve 50% and 80% of drug, namely T50 and T80, decreased from 138.0 min to 27.0 min, and the drug did not dissolve for 97.0 min in gastric media, respectively. Additionally, studies done in intestinal media have revealed T50 did not dissolve for 92.0 min. This work shows promise in incorporating functionalized nanoparticles into the crystal lattice of poorly soluble drugs to improve dissolution rate.

Antibiotic practices among household members and their domestic animals within rural communities in Cumilla district, Bangladesh: a cross-sectional survey.

BACKGROUND: Antibiotic resistance is a global threat to human health, and inappropriate use of antibiotics in humans and animals is widely considered to be a key driver of antibiotic resistant infections. Antibiotic use in humans and animals is growing rapidly in low- and, particularly, middle-income countries. However, there is little detailed understanding about practices related to the use of antibiotics in humans and animals within community settings in such countries. Here we aimed to understand the antibiotic practices of rural households across Cumilla district, Bangladesh, in relation to household members and their domestic animals. METHODS: In 2018 we conducted a cross-sectional survey using representative cluster sampling methods. We collected self-reported information from 682 female and 620 male household heads, with women also asked about their children's antibiotic practices. RESULTS: Only 48% (95% CI: 40, 56%) of women and men had heard of antibiotics, and among those women and men who were aware of antibiotics and the children of those women 70% (95% CI: 64, 76%) reported having previously taken antibiotics, while among these individuals who reported previously taking antibiotics 21% (95% CI: 18, 25%) said they had done so most recently within the last month. Risky/inappropriate antibiotic practices in humans and animals were often reported. For example, among women and men who were aware of antibiotics and the children of those women 52% (95% CI: 40, 63%) reported previously taking antibiotics for a "cough/cold", despite antibiotics being typically inappropriate for use against viral upper respiratory tract infections. Among poultry-owning respondents who were aware of antibiotics 11% (95% CI: 8, 15%) reported previously giving healthy poultry antibiotics, mainly for growth/prophylaxis, while among cattle-owning respondents who were aware of antibiotics and reported previously giving their cattle feed 20% (95% CI: 9, 37%) said the feed had contained antibiotics at least sometimes. CONCLUSIONS: Our results highlight the need for context-adapted interventions at both the community level and the health systems level to reduce inappropriate antibiotic use among humans and domestic animals in rural Bangladesh. Successfully reducing inappropriate use of antibiotics among humans and animals is a required and critical step in tackling antimicrobial resistance.

Immunohistochemical localization of VEGFR-2 in mouse mammary gland during reproductive cycle.

OBJECTIVE: The objective of this study was to obtain an insight into the role of the vascular endothelial growth factor (VEGF) in pregnancy-associated mammary epithelial development and angiogenesis. However, we examined the primary VEGF receptor (VEGFR-2) in the mouse mammary cycle. MATERIALS AND METHODS: The virgin (10-12 weeks), days 10 and 18 of pregnancy (P-10 and P-18), days 0, 5, 10, and 20 of lactation (L-0, L-5, L-10, and L-20), and days 5 and 10 of post-weaning (W-5 and W-10) stage were all used in this study. Immunohistochemistry and Western blotting were carried out on mammary tissues taken from three mice at each stage. RESULTS: VEGFR-2 was detected immunohistochemically in the cytoplasm of mammary epithelial and endothelial cells. Immunostaining for VEGFR-2 was consistently positive in mammary endothelial cells across all stages, whereas staining intensity in epithelial cells varied across the mammary cycle. Additionally, immunoblot analysis indicated a 220 kDa unique band of VEGFR-2 protein at all stages of the mammary cycle, with the maximum expression reported toward the end of pregnancy and gradually decreasing toward the end of lactation. CONCLUSION: In conclusion, the presence of VEGFR-2 in the mammary epithelium in addition to the endothelium suggests that VEGF plays an autocrine and paracrine role in the development, proliferation, and differentiation of the mammary epithelium during pregnancy.

Carbofuran accelerates the cellular senescence and declines the life span of spns1 mutant zebrafish.

Carbofuran is a carbamate pesticide, widely used in agricultural practices to increase crop productivity. In mammals, carbofuran is known to cause several untoward effects, such as apoptosis in the hippocampal neuron, oxidative stress, loss of memory and chromosomal anomalies. Most of these effects are implicated with cellular senescence. Therefore, the present study aimed to determine the effect of carbofuran on cellular senescence and biological ageing. Spinster homolog 1 (Spns1) is a transmembrane transporter, regulates autolysosomal biogenesis and plays a role in cellular senescence and survival. Using senescence-associated ß-galactosidase staining, we found that carbofuran accelerates the cellular senescence in spns1 mutant zebrafish. The yolk opaqueness, a premature ageing phenotype in zebrafish embryos, was accelerated by carbofuran treatment. In the survival study, carbofuran shortened the life span of spns1 mutant zebrafish. Autophagy is the cellular lysosomal degradation, usually up-regulated in the senescent cells. To know the impact of carbofuran exposure on autophagy progress, we established a double-transgenic zebrafish line, harbouring EGFP-tagged LC3-II and mCherry-tagged Lamp1 on spns1 mutant background, whereas we found, carbofuran exposure synergistically accelerates autolysosome formation with insufficient lysosome-mediated degradation. Our data collectively suggest that carbofuran exposure synergistically accelerates the cellular senescence and affects biological ageing in spns1 defective animals.

Reductive Degradation of CCl4 by Sulfidized Fe and Pd-Fe Nanoparticles: Kinetics, Longevity, and Morphology Aspects.

In this study a systematic comparison in morphology, long-term degradation, regeneration and reuse were conducted between palladized and sulfidized nanoscale zero-valent iron (Pd-Fe and S-Fe). Pd-Fe and S-Fe were prepared, after the synthesis of precursor Fe0 nanoparticles (spherical, ~35 nm radius) for carbon tetrachloride (CTC) treatment. With HAADF-TEM-EDS characterization, dispersive Pd islets were found on the Fe core of Pd-Fe. However, the Fe core was covered by the FeSx shell of S-Fe (FeS/FeS2 = 0.47). With an excessive Pd dose (10 mol%), the Pd-Fe were dramatically deformed to dendritic structures which significantly decreased reactivity. For CTC degradation, Pd-Fe (0.3 atomic% Pd) increased the degradation rate by 20-fold (ksa= 0.580 Lm-2min-1) while S-Fe presented a greater life time. The major intermediate chloroform (CF) was further degraded and less than 5% CF was observed after 24 h using Pd-Fe or S-Fe while above 50% CF remained using Fe. During aging, the Fe core was converted to FeOOH and Fe3O4/γ-Fe2O3. The restoration of Fe0 was achieved using NaBH4, which regenerated Fe and Pd-Fe. However, the formed FeSx shell on S-Fe was disappeared. The results suggest that S-Fe extends longevity of Fe, but the loss of FeSx after aging makes S-Fe eventually perform like Fe in terms of CTC degradation.

Mercury Removal from Wastewater Using Cysteamine Functionalized Membranes.

This study demonstrates a three-step process consisting of primary pre-filtration followed by ultrafiltration (UF) and adsorption with thiol-functionalized microfiltration membranes (thiol membranes) to effectively remove mercury sulfide nanoparticles (HgS NPs) and dissolved mercury (Hg2+) from wastewater. Thiol membranes were synthesized by incorporating either cysteine (Cys) or cysteamine (CysM) precursors onto polyacrylic acid (PAA)-functionalized polyvinylidene fluoride membranes. Carbodiimide chemistry was used to cross-link thiol (-SH) groups on membranes for metal adsorption. The thiol membranes and intermediates of the synthesis were tested for permeability and long-term mercury removal using synthetic waters and industrial wastewater spiked with HgS NPs and a Hg2+ salt. Results show that treatment of the spiked wastewater with a UF membrane removed HgS NPs to below the method detection level (<2 ppb) for up to 12.5 h of operation. Flux reductions that occurred during the experiment were reversible by washing with water, suggesting negligible permanent fouling. Dissolved Hg2+ species were removed to non-detection levels by passing the UF-treated wastewater through a CysM thiol membrane. The adsorption efficiency in this long-term study (>20 h) was approximately 97%. Addition of Ca2+ cations reduced the adsorption efficiencies to 82% for the CysM membrane and to 40% for the Cys membrane. The inferior performance of Cys membranes may be explained by the presence of a carboxyl (-COOH) functional group in Cys, which may interfere in the adsorption process in the presence of multiple cations because of multication absorption. CysM membranes may therefore be more effective for treatment of wastewater than Cys membranes. Focused ion beam characterization of a CysM membrane cross section demonstrates that the adsorption of heavy metals is not limited to the membrane surface but takes place across the entire pore length. Experimental results for adsorptions of selected heavy metals on thiol membranes over a wide range of operating conditions could be predicted with modeling. These results show promising potential industrial applications of thiol-functionalized membranes.

Antisolvent precipitative immobilization of micro and nanostructured griseofulvin on laboratory cultured diatom frustules for enhanced aqueous dissolution.

We report for the first time an antisolvent synthesis of nanostructured hydrophobic drug formulation onto a natural diatom. The jewel of the sea, a marine diatom, which is enriched in silicon, was cultured and grown in the laboratory. Its frustules were isolated and purified. The polar functional group on its surface provided unique physical and chemical properties. Griseofulvin (GF), an antifungal drug was used as a model compound was precipitated onto and adsorbed onto hydrophilic diatom surface, while stabilizer hydroxypropyl methyl cellulose (HPMC) was used for restricting particle growth during the composite synthesis. This work demonstrates that the fine drug crystals incorporated onto the diatom silica surface. The structural and morphological properties of the drug was characterized by various techniques. The drug loading of the formulation was estimated to be 41 % by weight. The incorporation of micro/nano crystals on the diatom surface dramatically enhanced the dissolution rate, and lowered the time required for 50 % dissolution for pure drug from 240-58 min for the drug composite, and the time required for 80 % dissolution or T80 was found to be 180 min for the composite while the pure drug reached a maximum of 65 % in 300 min.

Perceptions and experiences with district health information system software to collect and utilize health data in Bangladesh: a qualitative exploratory study.

BACKGROUND: Accurate and high-quality data are important for improving program effectiveness and informing policy. In 2009 Bangladesh's health management information system (HMIS) adopted the District Health Information Software, Version 2 (DHIS2) to capture real-time health service utilization data. However, routinely collected data are being underused because of poor data quality and reporting. We aimed to understand the facilitators and barriers to implementing DHIS2 as a way to retrieve meaningful and accurate data for reproductive, maternal, newborn, child, and adolescent health (RMNCAH) services. METHODS: This qualitative study was conducted in two districts of Bangladesh from September 2017 to 2018. Data collection included key informant interviews (n = 11), in-depth interviews (n = 23), and focus group discussions (n = 2). The study participants were involved with DHIS2 implementation from the community level to the national level. The data were analyzed thematically. RESULTS: DHIS2 could improve the timeliness and completeness of data reporting over time. The reported facilitating factors were strong government commitment, extensive donor support, and positive attitudes toward technology among staff. Quality checks and feedback loops at multiple levels of data gathering points are helpful for minimizing data errors. Introducing a dashboard makes DHIS2 compatible to use as a monitoring tool. Barriers to effective DHIS2 implementation were lack of human resources, slow Internet connectivity, frequent changes to DHIS2 versions, and maintaining both manual and electronic system side-by-side. The data in DHIS2 remains incomplete because it does not capture data from private health facilities. Having two parallel HMIS reporting the same RMNCAH indicators threatens data quality and increases the reporting workload. CONCLUSION: The overall insights from this study are expected to contribute to the development of effective strategies for successful DHIS2 implementation and building a responsive HMIS. Focused strategic direction is needed to sustain the achievements of digital data culture. Periodic refresher trainings, incentives for increased performance, and an automated single reporting system for multiple stakeholders could make the system more user-friendly. A national electronic health strategy and implementation framework can facilitate creating a culture of DHIS2 use for planning, setting priorities, and decision making among stakeholder groups.

Direct incorporation of nano graphene oxide (nGO) into hydrophobic drug crystals for enhanced aqueous dissolution.

This paper reports the development of a successful anti-solvent method that incorporates colloidal nano scale graphene oxide (nGO) directly into hydrophobic drug crystals. The nGO dispersed in solution acted as nucleating sites for crystallization and were embedded into the drug crystals without altering its structure or physical properties such as melting point. Several composites of drugs Sulfamethoxazole and Griseofulvin were synthesized with nGO concentration ranging between 0.2 and 1.0 %. The presence of nGO dramatically enhanced the dissolution rate. The time needed to reach a 50 % release (T50) reduced from 42-14 min with the integration of 0.8 % nGO in SMZ, while in GF the reduction was from 44-27 min with 0.5 % nGO. Increased release rates are attributed to the presence of the hydrophilic nGO which hydrogen bond more so with the aqueous mediums. Therefore, the incorporation of nGO into poorly soluble drugs is an effective approach towards drug delivery and bioavailability improvement and opens a new approach to high performance drug delivery.

Secure and Provenance Enhanced Internet of Health Things Framework: A Blockchain Managed Federated Learning Approach.

Recent advancements in the Internet of Health Things (IoHT) have ushered in the wide adoption of IoT devices in our daily health management. For IoHT data to be acceptable by stakeholders, applications that incorporate the IoHT must have a provision for data provenance, in addition to the accuracy, security, integrity, and quality of data. To protect the privacy and security of IoHT data, federated learning (FL) and differential privacy (DP) have been proposed, where private IoHT data can be trained at the owner's premises. Recent advancements in hardware GPUs even allow the FL process within smartphone or edge devices having the IoHT attached to their edge nodes. Although some of the privacy concerns of IoHT data are addressed by FL, fully decentralized FL is still a challenge due to the lack of training capability at all federated nodes, the scarcity of high-quality training datasets, the provenance of training data, and the authentication required for each FL node. In this paper, we present a lightweight hybrid FL framework in which blockchain smart contracts manage the edge training plan, trust management, and authentication of participating federated nodes, the distribution of global or locally trained models, the reputation of edge nodes and their uploaded datasets or models. The framework also supports the full encryption of a dataset, the model training, and the inferencing process. Each federated edge node performs additive encryption, while the blockchain uses multiplicative encryption to aggregate the updated model parameters. To support the full privacy and anonymization of the IoHT data, the framework supports lightweight DP. This framework was tested with several deep learning applications designed for clinical trials with COVID-19 patients. We present here the detailed design, implementation, and test results, which demonstrate strong potential for wider adoption of IoHT-based health management in a secure way.

Functional analysis of monocarboxylate transporter 8 mutations in Japanese Allan-Herndon-Dudley syndrome patients.

Monocarboxylate transporter 8 (MCT8) facilitates T3 uptake into cells. Mutations in MCT8 lead to Allan-Herndon-Dudley syndrome (AHDS), which is characterized by severe psychomotor retardation and abnormal thyroid hormone profile. Nine uncharacterized MCT8 mutations in Japanese patients with severe neurocognitive impairment and elevated serum T3 levels were studied regarding the transport of T3. Human MCT8 (hMCT8) function was studied in wild-type (WT) or mutant hMCT8-transfected human placental choriocarcinoma cells (JEG3) by visualizing the locations of the proteins in the cells, detecting specific proteins, and measuring T3 uptake. We identified 6 missense (p.Arg445Ser, p.Asp498Asn, p.Gly276Arg, p.Gly196Glu, p.Gly401Arg, and p.Gly312Arg), 2 frameshift (p.Arg355Profs*64 and p.Tyr550Serfs*17), and 1 deletion (p.Pro561del) mutation(s) in the hMCT8 gene. All patients exhibited clinical characteristics of AHDS with high free T3, low-normal free T4, and normal-elevated TSH levels. All tested mutants were expressed at the protein level, except p.Arg355Profs*64 and p.Tyr550Serfs*17, which were truncated, and were inactive in T3 uptake, excluding p.Arg445Ser and p.Pro561del mutants, compared with WT-hMCT8. Immunocytochemistry revealed plasma membrane localization of p.Arg445Ser and p.Pro561del mutants similar with WT-hMCT8. The other mutants failed to localize in significant amount(s) in the plasma membrane and instead localized in the cytoplasm. These data indicate that p.Arg445Ser and p.Pro561del mutants preserve residual function, whereas p.Asp498Asn, p.Gly276Arg, p.Gly196Glu, p.Gly401Arg, p.Gly312Arg, p.Arg355Profs*64, and p.Tyr550Serfs*17 mutants lack function. These findings suggest that the mutations in MCT8 cause loss of function by reducing protein expression, impairing trafficking of protein to plasma membrane, and disrupting substrate channel.

Expression Patterns of Host Inflammatory Cytokine Genes during Infestation with Haemaphysalis longicornis, a Zoonotic Vector, in Blood Sucking Periods.

Tick saliva is critically important for continuous attachment to the host, blood feeding for days, and transmission of tick-borne pathogens. To characterize the patterns of inflammatory cytokine gene expression during its attachment and blood sucking time, peripheral blood samples of rabbits infested with Haemaphysalis longicornis ticks were collected at different intervals. Blood histamine concentration was evaluated as well as gene encoding IFN-γ, TNF-α, IL-2, IL-6, IL-4, and IL-10 were compared with non-infested rabbits. Blood histamine concentration of tick-infested rabbits during fast feeding time was significantly higher than that of non-infested rabbits. In both nymph and adult tick infested rabbits, expression of TNF-α and IFN-γ genes were decreased significantly (P<0.05), while expression of IL-4, IL-6, and IL-10 were increased 1.3 to 7 folds in adult infested rabbits with the exception of IL-6 that was significantly (P<0.05) decreased in nymph infested rabbits. IL-2 was not expressed in either nymph or adult infestation. H. longicornis saliva is capable of modulate host responses through a complex correlation with histamine and Th1, Th2 mediated cytokines that suppress the inflammatory responses directed toward inflammatory mediators introduced into the host during tick feeding.

Screening for obstructive sleep apnoea using the STOPBANG questionnaire and the Epworth sleepiness score in patients admitted on the unselected acute medical take in a UK hospital.

Obstructive sleep apnoea (OSA), which is often overlooked in patients presenting to primary and secondary care, is an increasingly common comorbidity. The prevalence of OSA has not been studied in the unselected acute medical take. The aim of this study was to screen for the prevalence of undiagnosed OSA using the STOPBANG Questionnaire and the Epworth sleepiness scale (ESS) score in an unselected acute medical take. This was a cross-sectional study in a busy UK general hospital. Patient demographics, comorbidities, ESS and STOPBANG scores on unselected acute medical takes were reviewed and analysed to assess the prevalence of OSA. Of 93 patients screened, more than 50% were obese. The STOPBANG score was ≥3 in 73%. The ESS was significantly increased (≥11) in 20%. On multivariate analysis, ESS continued to remain independently associated with the STOPBANG score with a p-value of 0.04. The routine use of the STOPBANG questionnaire followed by an ESS score in those with a score of ≥3 may focus evaluation for undetected OSA in the acute medical care setting.