Total soluble HLA class I and soluble HLA-G in multiple myeloma and monoclonal gammopathy of undetermined significance.

Serum beta2-microglobulin, the light chain of the HLA class I molecular complex, remains one of the best survival prognostic factors in multiple myeloma, but other HLA class I molecules might be of interest in monoclonal gammopathies. In this study, we evaluate total soluble HLA class I (HLA-Is) and soluble HLA-G (HLA-Gs) in 103 patients with newly diagnosed multiple myeloma, 30 patients with monoclonal gammopathy of undetermined significance (MGUS), and 30 healthy subjects, studying their prognostic value in multiple myeloma. In multiple myeloma patients, HLA-Is and HLA-Gs median values were 0.8 microg/mL and 28 ng/mL, respectively. Median HLA-Is concentration was higher in stage II and III multiple myeloma patients than in stage I multiple myeloma, MGUS, and control patients. Median HLA-Gs was significantly lower in healthy controls than in MGUS and multiple myeloma patients. A high level of HLA-Is (> or =2.1 microg/mL) was predictive of short survival (P = 0.017). For each given level of beta2-microglobulin, the relative risk of death was higher for patients with HLA-Is > or = 2.1 microg/mL than in patients with a lower level (P = 0.047). HLA-Gs, a marker of monoclonal gammopathy, was of no prognostic value, but the addition of HLA-Is to beta2-microglobulin produced an efficient prognostic score (P < 0.0001). HLA-Is is a new marker of multiple myeloma tumor load and provides additional survival prognostic information to beta2-microglobulin.     

Are Essential Medicines in Malaysia Accessible, Affordable and Available?

Objective: To assess the pharmaceutical sector to know whether people have access to essential medicines. Setting: The study was conducted in 20 public health clinics, five public district drug stores and 20 private retail pharmacies selected randomly in five different areas randomly selected (four states and a federal territory). Method: The methodology used was adopted from the World Health Organization study protocol. The degree of attainment of the strategic pharmaceutical objectives of improved access is measured by a list of tested indicators. Access is measured in terms of the availability and affordability of essential medicines, especially to the poor and in the public sector. The first survey in the public health clinics and public district drug stores gathered information about current availability of essential medicines, prevalence of stock-outs and affordability of treatment (except drug stores). The second survey assessed affordability of treatment in public health clinics and private retail pharmacies. Main Outcome Measure Availability, stock-out duration, percent of medicines dispensed, accessibility and affordability of key medicines. Results The average availability of key medicines in the public health clinics for the country was 95.4%. The average stock-out duration of key medicines was 6.5 days. However, average availability of key medicines in the public district drug stores was 89.2%; with an average stock-out duration of 32.4 days. Medicines prescribed were 100% dispensed to the patients. Average affordability for public health clinics was 1.5 weeks salary and for the private pharmacies, 3.7 weeks salary. Conclusions: The present pharmaceutical situation in the context of essential medicines list implementation reflected that the majority of the population in Malaysia had access to affordable essential medicines. If medicines need to be obtained from the private sector, they are hardly affordable. Although the average availability of essential medicines in Malaysia was high being more than 95.0%, in certain areas in Sabah availability was less than 80.0% and still a problem.     

Label-free metabolic imaging of non-alcoholic-fatty-liver-disease (NAFLD) liver by volumetric dynamic optical coherence tomography

Label-free metabolic imaging of non-alcoholic fatty liver disease (NAFLD) mouse liver is demonstrated ex vivo by dynamic optical coherence tomography (OCT). The NAFLD mouse is a methionine choline-deficient (MCD)-diet model, and two mice fed the MCD diet for 1 and 2 weeks are involved in addition to a normal-diet mouse. The dynamic OCT is based on repeating raster scan and logarithmic intensity variance (LIV) analysis that enables volumetric metabolic imaging with a standard-speed (50,000 A-lines/s) OCT system. Metabolic domains associated with lipid droplet accumulation and inflammation are clearly visualized three-dimensionally. Particularly, the normal-diet liver exhibits highly metabolic vessel-like structures of peri-vascular hepatic zones. The 1-week MCD-diet liver shows ring-shaped highly metabolic structures formed with lipid droplets. The 2-week MCD-diet liver exhibits fragmented vessel-like structures associated with inflammation. These results imply that volumetric LIV imaging is useful for visualizing and assessing NAFLD abnormalities.     

Long-Term Effect of Gluten-Free Diets on Nutritional Status,Body Composition,and Associated Factors in Adult Saudi Females with Celiac Disease

This cross-sectional study examines the influence of long-term gluten-free diet (GFD) consumption on nutritional status, body composition, and associated factors in adult Saudi females with celiac diseases (CD). Fifty-one patients who have been diagnosed with CD and have been on GFD for more than 1 year were included in this study where data regarding their dietary pattern, as well as a complete analysis of their anthropometric parameters, vitamins B12 and D levels, and complete blood count (CBC), were collected. Data have shown that all included patients showed a reduced intake in all micro and macro-nutrients, as well as vitamin D, folate, calcium, and iron. However, the vast majority of all measured hematological parameters and blood indices were within the expected reference range. In addition, 51%, 43.1%, and 60.8% of the patients showed low waist/hip ratio (WHR), decreased level of total body fat (BF), and decreased level of visceral fat (VF), respectively, whereas 33.3% were slim. The poor educational level and some psychosocial factors were associated with the poor nutritional status of the patients. In conclusion, the GFD-dependent intake by female patients with CD adversely affects their nutritional intake and anthropometric indices and leads to a deficiency in major nutrients, vitamins, and ions.     

DMAIC methodology for achieving public satisfaction with health departments in various districts of Punjab and optimizing CT scan patient load in urban city hospitals

The health care delivery system in Pakistan is in a process of rapid growth, and it consists of public and private sectors. The provincial government is preliminarily responsible for providing health care facilities within its province except in federally administered areas. In Pakistan, there are three tiers of governmental healthcare delivery systems, which comprise government, semi-government, and parastatal organizations. The purpose of this study is to understand the rapid increase in influx of patients in major city hospitals of the Punjab province. The reasons for patient flow towards the major city areas can vary, but our point of focus is mainly on those patients who are prescribed to get a computed tomography (CT) scan done for better diagnosis and early treatment, including but not limited to roadside accident cases. The study targets the define, measure, analyze, improve and control (DMAIC) problem solving approach to assess the potential cause of CT patient flow and the challenges that the health department is facing to cater to such a patient niche and process while minimizing the congestion in city government hospitals. The approach in this study summarizes with numerous quality tools like Voice of Customer (VOC) which is customer feedback, Customer Output Process Input and Supplier (COPIS) processes use for high-level process map to know what your customer value, Approver Resource Member Interested (ARMI) chart which is use to analyze the stakeholders on management of the project, evaluation with the help of fishbone diagram and house of quality, and for process improvement methodology we use the team brainstorming technique and the kaizen 5-why technique. The technique came up with an idea of a public-private partnership (PPP) project—partnership between public agency and private firm, as the health care industry in Punjab province is going through budgetary issues. In a PPP project, the Government will allocate the space to a private firm to build the facility on their own and provide quality service for CT scan diagnosis to the public of Punjab. The study identified the top 10 critical factors that the patients have expected from the government to be provided on priority. The Kaizen process improvement methodology has been adopted to provide the possible solution of government budgetary issues. The set of tools in this study can be adopted by other PPP projects to enhance the project performance.     

Superior quality chemically reduced graphene oxide for high performance EMI shielding materials

The chemical reduction process of graphene oxide combined with a mild and controllable thermal treatment under vacuum at 200 °C for 4 hours provided a cost-effective, scalable, and high-yield route for Reduced Graphene Oxide (RGO) industrial production and became a potential candidate for producing electromagnetic interference (EMI) shielding. We investigated graphite, and RGO using l-ascorbic acid and Sodium borohydride before and after thermal treatment by carefully evaluating the chemical and morphological structures. The thermally treated l-ascorbic Acid reduction route (TCRGOL) conductivity was 2.14 × 10³ S m⁻¹ and total shielding efficiency (SET) based on mass loadings per area of shielding was 94 dB with about one-tenth less graphite weight and surpassing other graphene reduction mechanisms in the frequency range of 8.2–12.4 GHz, i.e., X-band, at room temperature while being tested using the waveguide line technique. The developed treatment represents valuable progress in the path to chemical reduction using a safe reducing agent and offering superior quality RGO rarely achieved with the top-down technique, providing a high EMI shielding performance.

The developed two-step protocol offers a superior reduced graphene oxide TCRGOL quality (7 layers), and its SET was 94 dB over the X-band.     

Magnetic Metal Oxide-Based Photocatalysts with Integrated Silver for Water Treatment

In this review, the most recent advances in the field of magnetic composite photocatalysts with integrated plasmonic silver (Ag) is presented, with an overview of their synthesis techniques, properties and photocatalytic pollutant removal applications. Magnetic attributes combined with plasmonic properties in these composites result in enhancements for light absorption, charge-pair generation-separation-transfer and photocatalytic efficiency with the additional advantage of their facile magnetic separation from water solutions after treatment, neutralizing the issue of silver’s inherent toxicity. A detailed overview of the currently utilized synthesis methods and techniques for the preparation of magnetic silver-integrated composites is presented. Furthermore, an extended critical review of the most recent pollutant removal applications of these composites via green photocatalysis technology is presented. From this survey, the potential of magnetic composites integrated with plasmonic metals is highlighted for light-induced water treatment and purification. Highlights: (1) Perspective of magnetic properties combined with plasmon metal attributes; (2) Overview of recent methods for magnetic silver-integrated composite synthesis; (3) Critical view of recent applications for photocatalytic pollutant removal.     

Targeted Mutations in the Fusion Peptide Region of La Crosse Virus Attenuate Neuroinvasion and Confer Protection against Encephalitis

La Crosse virus (LACV) is a major cause of pediatric encephalitis and aseptic meningitis in the Midwestern, Mid-Atlantic, and Southern United States, where it is an emerging pathogen. The LACV Gc glycoprotein plays a critical role in the neuropathogenesis of LACV encephalitis as the putative virus attachment protein. Previously, we identified and experimentally confirmed the location of the LACV fusion peptide within Gc and generated a panel of recombinant LACVs (rLACVs) containing mutations in the fusion peptide as well as the wild-type sequence. These rLACVs retained their ability to cause neuronal death in a primary embryonic rat neuronal culture system, despite decreased replication and fusion phenotypes. To test the role of the fusion peptide in vivo, we tested rLACVs in an age-dependent murine model of LACV encephalitis. When inoculated directly into the CNS of young adult mice (P28), the rLACV fusion peptide mutants were as neurovirulent as the rLACV engineered with a wild-type sequence, confirming the results obtained in tissue culture. In contrast, the fusion peptide mutant rLACVs were less neuroinvasive when suckling (P3) or weanling (P21) mice were inoculated peripherally, demonstrating that the LACV fusion peptide is a determinant of neuroinvasion, but not of neurovirulence. In a challenge experiment, we found that peripheral challenge of weanling (P21) mice with fusion peptide mutant rLACVs protected from a subsequent WT-LACV challenge, suggesting that mutations in the fusion peptide are an attractive target for generating live-attenuated virus vaccines. Importantly, the high degree of conservation of the fusion peptide amongst the Bunyavirales and, structurally, other arboviruses suggests that these findings are broadly applicable to viruses that use a class II fusion mechanism and cause neurologic disease.     

Weekly Nowcasting of New COVID-19 Cases Using Past Viral Load Measurements

The rapid spread of the coronavirus disease COVID-19 has imposed clinical and financial burdens on hospitals and governments attempting to provide patients with medical care and implement disease-controlling policies. The transmissibility of the disease was shown to be correlated with the patient’s viral load, which can be measured during testing using the cycle threshold (Ct). Previous models have utilized Ct to forecast the trajectory of the spread, which can provide valuable information to better allocate resources and change policies. However, these models combined other variables specific to medical institutions or came in the form of compartmental models that rely on epidemiological assumptions, all of which could impose prediction uncertainties. In this study, we overcome these limitations using data-driven modeling that utilizes Ct and previous number of cases, two institution-independent variables. We collected three groups of patients (n = 6296, n = 3228, and n = 12,096) from different time periods to train, validate, and independently validate the models. We used three machine learning algorithms and three deep learning algorithms that can model the temporal dynamic behavior of the number of cases. The endpoint was 7-week forward number of cases, and the prediction was evaluated using mean square error (MSE). The sequence-to-sequence model showed the best prediction during validation (MSE = 0.025), while polynomial regression (OLS) and support vector machine regression (SVR) had better performance during independent validation (MSE = 0.1596, and MSE = 0.16754, respectively), which exhibited better generalizability of the latter. The OLS and SVR models were used on a dataset from an external institution and showed promise in predicting COVID-19 incidences across institutions. These models may support clinical and logistic decision-making after prospective validation.