Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19.

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood. METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models. RESULTS: Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P < .001), and a steeper rate of decline through the first 5 days (P < .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale. CONCLUSIONS: Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed. CLINICAL TRIALS REGISTRATION: NCT04501978.

Effectiveness of ab initio molecular dynamics in simulating EXAFS spectra from layered systems.

The simulation of EXAFS spectra of thin films via ab initio methods is discussed. The procedure for producing the spectra is presented as well as an application to a two-dimensional material (WSe2) where the effectiveness of this method in reproducing the spectrum and the linear dichroic response is shown. A series of further examples in which the method has been employed for the structural determination of materials are given.

Temperature-dependent dielectric relaxations and transport properties of Sm3+ & La3+ doped Bi-oxide nanoparticles.

The suggested novel rare-earth doped bismuth calcium cobaltites Bi2Ca2-2xSmxLaxCoO6 (x = 0.000-0.075) were synthesized by a co-precipitation route. XRD was utilized for structural information. SEM and EDX were used for microstructural and elemental analysis. AC conductivities (σac) were measured at temperatures of 100-500 °C. The σac of all synthesized samples increased as the temperature increased, indicating that they are semi-conductive. The conduction process of all the synthesized samples was examined using Jonscher's power law. The spreading factor and relaxation time of all the synthesized samples were studied using nonlinear Debye fitting. At a high temperature of 500 °C, the dielectric curve showed anomalous behaviour that was related to the negative values of the dielectric constant at 500 kHz-3 MHz. The studied (Sm-La)-doped samples showed higher values of the dielectric constant (1.03 × 108). The Cole-Cole plot used in the impedance investigation reveals that as the temperature rises, the diameter of the arcs decreases, implying a drop in impedance and rises in conductivity. The growing trend of DC electrical conductivity with temperature depicts the semi-conductive nature of the synthesized materials.

Effect of copper doping on plasmonic nanofilms for high performance photovoltaic energy applications.

In the current era, alternative but environment-friendly sources of energy have gained attention to meet the growing energy demands. In particular, the focus of research has been solar energy and using it to fulfill energy demands. Solar energy is either directly converted into electrical energy or stored for later use. Solar cells are a practical way to turn solar energy into electrical energy. Various materials are being investigated to manufacture solar cell devices that can absorb a maximum number of photons present in sunlight. The present study reports thermally evaporated in situ Cu-doped SnS photon absorber thin films with tunable physical properties. This study mainly explored the effects of changing Cu concentrations on the physical features of light absorption of SnS thin films. The thin films were formed by simultaneous resistive heating of Cu and SnS powders on glass substrates at 150 °C. The X-ray diffraction patterns revealed pure SnS thin films having orthorhombic polycrystalline crystal structures oriented preferentially along the (111) plane. Raman spectroscopy confirmed this phase purity. Photoconductivity studies showed phase dependence on Cu content that improved with increasing concentrations of Cu. The optical bandgap energy was also found to be dependent on Cu content and was observed at 1.10-1.47 eV for SnS thin films with variation in the Cu content, i.e., 0-18%. According to the hot probe method, all films displayed p-type conductivity for the substitution of Cu metal atoms. These findings demonstrated that the prepared thin films are substantial candidates as low-cost, suitably efficient, thin-film solar cells featuring environmentally-friendly active layers that absorb sunlight.

The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19.

BACKGROUND: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19. OBJECTIVE: To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2. DESIGN: Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge. SETTING: 114 centers in 10 countries. PARTICIPANTS: Adults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms. MEASUREMENTS: Baseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma antigen levels were assessed using both unadjusted and multivariable modeling. Association between elevated baseline antigen level of 1000 ng/L or greater and outcomes, including worsening of ordinal pulmonary scale at day 5 and time to hospital discharge, were evaluated using logistic regression and Fine-Gray regression models, respectively. RESULTS: Plasma antigen was below the level of quantification in 5% of participants at enrollment, and 1000 ng/L or greater in 57%. Baseline pulmonary severity of illness was strongly associated with plasma antigen level, with mean plasma antigen level 3.10-fold higher among those requiring noninvasive ventilation or high-flow nasal cannula compared with room air (95% CI, 2.22 to 4.34). Plasma antigen level was higher in those who lacked antispike antibodies (6.42 fold; CI, 5.37 to 7.66) and in those with the Delta variant (1.73 fold; CI, 1.41 to 2.13). Additional factors associated with higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. In contrast, race, ethnicity, body mass index, and immunocompromising conditions were not associated with plasma antigen levels. Plasma antigen level of 1000 ng/L or greater was associated with a markedly higher odds of worsened pulmonary status at day 5 (odds ratio, 5.06 [CI, 3.41 to 7.50]) and longer time to hospital discharge (median, 7 vs. 4 days; subhazard ratio, 0.51 [CI, 0.45 to 0.57]), with subhazard ratios similar across all levels of baseline pulmonary severity. LIMITATIONS: Plasma samples were drawn at enrollment, not hospital presentation. No point-of-care test to measure plasma antigen is currently available. CONCLUSION: Elevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes. Multiple clinical and viral factors are associated with plasma antigen level at presentation. These data support a potential role of ongoing viral replication in the pathogenesis of SARS-CoV-2 in hospitalized patients. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

Phytochemical profiling, in vitro and in vivo anti-inflammatory, analgesic and antipyretic potential of Sesuvium sesuvioides (Fenzl) Verdc. (Aizoaceae).

Sesuvium sesuvioides (Fenzl) Verdc is traditionally used in the treatment of inflammatory diseases such as arthritis and gout The aim of present study was to assess the possible anti-inflammatory, analgesic and antipyretic potential of the methanol extract of Sesuvium sesuvioides (SsCr) to prove scientifically its folklore use in the inflammatory diseases and to screen its total antioxidant capacity by multiple methods and phytocompounds by GC-MS. The preliminary phytochemical studies showed the presence of phenols, flavonoids, glycosides, coumarin, terpenoids, saponins, fats and carbohydrates in crude extract. The total phenolic contents (27.31 ± 0.28 mg GAE/g) and total flavonoids (3.58 ± 0.12 mgRE/g) values were observed. The antioxidant capacity of SsCr showed significant DPPH, ABTS, CUPRAC, FRAP, PBD and metal chelating results. GC-MS analysis displayed the phytoconstituents with anti-inflammatory potentials such as 2-methoxy-4-vinylphenol, vanillin, umbelliferone, methyl ferulate, palmitoleic acid, methyl palmitate and phytol. SsCr presented noteworthy HRBC membrane stability with maximum inhibition of cell hemolysis (47.79%). In carrageenan-induced hind paw edema assay result showed dose-dependent anti-inflammatory action. SsCr presented significant (p < 0.05) analgesic activity in hot-plate and tail flicking tests similarly it also showed the noteworthy inhibition in pain latency against formalin induced analgesia at 1st and 2nd phases. SsCr reduced the acetic acid-induced writhes at different doses (250, 500 and 750 mg). Results of antipyretic activity of SsCr extract were significant at 500 and 750 mg. The results of in vitro and in vivo experimental studies verified the anti-inflammatory, analgesic and antipyretic potential of Sesuvium sesuvioides and supported the folklore uses of this plant.

Pharmacognostic screening, physico-chemical and cytotoxic potential of Sesuvium sesuvioides (Fenzyl) Verdc.

Sesuvium sesuvioides(Fenzl) Verdc. (Aizoaceae) is commonly known as BarriUlwaiti and used in folklore remedies; i.e. arthritis, gout, epistaxis, hemorrhage, smallpox, chickenpox, cold and flu by the local practitioners in the Cholistan desert. In the current study, fresh and dried plant material was examined macroscopically and microscopically. Transverse sections of plant parts such as leaf, stem, root and flower were also examined. Physico-chemical and fluorescence analysis according to WHO recommendations for standardization of plant material were performed. Phytochemical screening maybe helpful in determining the secondary metabolites responsible for their biological activities. Mineral analysis (Na+, K+, Li+, Ca2+, Mg2+, Cl-, Zn2+, Cu2+ and Fe2+), total fat and crude proteins were estimated to evaluate the nutritional value of the plant. In in-vitro cytotoxic activity, n-hexane fraction (50µg) showed significant results against Human T-lymphoblastic Leukemia CCRF-CEM cell lines followed by methanol and chloroform fractions. This study will be worthwhile for the correct identification and for observing any type of adulteration. This observation will be helpful for differentiating this species from closely related species of the same genus or family.

Structural, dielectric and electrical properties of Gd-substituted lithium nano-ferrites prepared by the WOWS sol-gel method.

To synthesize lithium ferrite with various Gd concentrations (Li0.5Fe2.5-xGdxO4), x = 0.00, 0.025, 0.05, 0.075, 0.1, solutes were dissolved in glycol, i.e. by using the without water and surfactant (WOWS) sol-gel method. X-ray diffraction (XRD) analysis confirmed that the material possessed an inverse spinel cubic structure and is single phase. Pellets of all samples were sintered at 700 °C and XRD confirmed that samples were crystalline, phase pure and had an inverse spinel cubic lattice. Scanning electron microscopy indicated that the grains were agglomerated and had a predominantly spherical shape. It is concluded that Gd acts as a grain refiner in lithium ferrite up to a Gd concentration of 0.05. AC conductivity and dielectric constant increased by increasing Gd concentration. The Maxwell-Wagner model and Johnsher's power law were used to explain the dielectric properties. DC conductivity was measured from 100 to 600 °C. DC conductivity was explained by the hopping mechanism. It is concluded that DC resistivity and dielectric constant values are related reciprocally in the prepared sample. AC electrical properties were also measured at a constant frequency of 1 MHz in the temperature range from 400 to 600 °C. Gd-substituted lithium ferrite showed high AC conductivity, high DC resistivity and constant dielectric values, but low dielectric loss values as compared to pure lithium ferrite.

Peripheral neuropathy in Parkinson's disease.

Peripheral neuropathy (PN) is a common neurological problem defined as a dysfunction of sensory, motor, and autonomic nerves. The presence of peripheral neuropathy has recently been noticed in Parkinson's disease (PD) This comorbidity is concerning as it increases the burden on patients whose motor functions are previously compromised. A comprehensive computer-based literature review utilizing multiple peer-reviewed databases (e.g., Embase, PsycINFO, CINAHL, etc.) was conducted. There is evidence for the utility of robust diagnostic criteria to distinguish between large fiber neuropathy (LFN) and small fiber neuropathy (SFN). Some studies have established links between prolonged L-DOPA exposure and prevalence with increased levels of homocysteine (HCY) and methylmalonic acid (MMA) as pathological underlying mechanisms. PN in PD patients with relatively truncated exposure to L-DOPA therapy may have underlying mutations in the Parkin and MHTFR gene or separate mitochondrial disorders. Vitamin B12 and cobalamin deficiencies have also been implicated as drivers of PN. Accumulation of phosphorylated α-synuclein is another central feature in PN and deems urgent exploration via large cohort studies. Importantly, these underlying mechanisms have been linked to peripheral denervation. This review delves into the potential treatments for PN targeting B12 deficiencies and the use of COMT inhibitors along with other novel approaches. Avenues of research with powerful randomized controlled and long-term cohort studies exploring genetic mechanisms and novel treatment pathways is urgently required to alleviate the burden of disease exerted by PN on PD.

The Future of Neurocritical Care Research: Proceedings and Recommendations from the Fifth Neurocritical Care Research Network Conference.

The Fifth Neurocritical Care Research Network (NCRN) Conference held in Boca Raton, Florida, in September of 2018 was devoted to challenging the current status quo and examining the role of the Neurocritical Care Society (NCS) in driving the science and research of neurocritical care. The aim of this in-person meeting was to set the agenda for the NCS's Neurocritical Care Research Central, which is the overall research arm of the society. Prior to the meeting, all 103 participants received educational content (book and seminar) on the 'Blue Ocean Strategy®,' a concept from the business world which aims to identify undiscovered and uncontested market space, and to brainstorm innovative ideas and methods with which to address current challenges in neurocritical care research. Three five-member working groups met at least four times by teleconference prior to the in-person meeting to prepare answers to a set of questions using the Blue Ocean Strategy concept as a platform. At the Fifth NCRN Conference, these groups presented to a five-member jury and all attendees for open discussion. The jury then developed a set of recommendations for NCS to consider in order to move neurocritical care research forward. We have summarized the topics discussed at the conference and put forward recommendations for the future direction of the NCRN and neurocritical care research in general.

Cell proliferation activity delineated by molecular docking of four new compounds isolated from the aerial parts of Suaeda monoica Forssk. ex. J.F. Gmel.

Using different chromatographic methods, four new compounds were isolated from the aerial parts of Suaeda monoica (Chenopodiaceae) along with 2-hydroxy-1-naphthoic acid (SCM-3). The structures of the new compounds were established as 6'-hydroxy-10'-geranilanyl naphtha-1-oate (SMC-1), 4,4,8ß,10ß-Tetramethyl-9ß-isobutanyl decalin-13-ol-13-O-ß-D-xylopyranoside (SCM-2), 6'-(2-hydroxynaphthalen-3-yl) hexanoic acid (SCM-4) and 1'-(2-Methoxy-3-naphthyl)-4'-(2''-methylbenzoyl)-n-butane (SMC-5) by IR, EIMS and NMR (1 & 2D) analyses. All compounds (50 µg/mL) were tested for cell proliferative potential on cultured human liver cell HepG2 cells by MTT assay. The results revealed a marked cell proliferative potential of all compounds (1.42-1.48 fold) as compared to untreated control. The results of molecular docking and binding with specific proteins such as PTEN (Phosphatase and Tensin homolog) and p53 also justify the cell proliferative potential of the isolated compounds. Glide program with Schrodinger suit 2018 was used to evaluate the binding between SMC compounds and proteins (PTEN and p53). The binding affinity of all compounds was in order of 104-105 M-1 towards both PTEN and p53. All the SMC compounds have been found to bind at the active site of PTEN, thereby may prevent the binding of phosphatidylinositiol 3,4,5-triphosphate (PI3P). In the locked position, PTEN would not be able to hydrolyze PI3P and hence the PI3P regulated signaling pathway remains active. Similarly, SMC molecules were found to interact with the amino acid residues (Ser99, Thr170, Gly199, and Asp224) which are critically involved in the formation of tetrameric p53. The blockage of p53 to attain its active conformation thus may prevent the recruitment of p53 on DNA and hence may promote cell proliferation.

Quantitative analysis of Fuller's earth using laser-induced breakdown spectroscopy and inductively coupled plasma/optical emission spectroscopy.

Fuller's earth, most commonly known as Multani Matti (clay) in Urdu, among its various utilizations is traditionally used in skin care cosmetics, particularly for removing blackheads and to treat oily skin. It is also used for improving skin complexion. In this paper, laser-induced breakdown spectroscopy (LIBS) was effectively employed for the quantitative investigation of various clay samples for their special uses. To get the LIBS spectra with an optimal signal-to-noise as well as for a more robust and accurate analytical investigation, different experimental parameters (laser energy, gate delay time, and the distance between target and focusing lens) were optimized before the experiments on actual samples. The analysis of emission spectra revealed the presence of many different elements, including Al, Ca, Fe, Mg, Mn, Na, K, Li, S, Si, and Zn. The electron number density and plasma temperatures were determined using the Stark broadened line profile and Boltzmann plot method, respectively. To determine the relative concentration of observed elements, we used an integrated intensity ratio method, integrated intensity of every line from all elements, and calibration free (CF)-LIBS. The prevailing condition of local thermodynamic equilibrium during the experimental executions was verified with multiple criteria. The spectral lines used in CF-LIBS were characterized for the influence from the self-absorption phenomenon, but the same was found insignificant. The findings of our LIBS system were found to agree excellently with the outcomes of the inductively coupled plasma/optical emission spectroscopy, thereby yielding a high statistical correlation factor and hence enlighten the significance of LIBS as a safe and reliable tool for elemental analysis of clay samples.

Spatio-temporal numerical modeling of reaction-diffusion measles epidemic system.

In this work, we investigate the numerical solution of the susceptible exposed infected and recovered measles epidemic model. We also evaluate the numerical stability and the bifurcation value of the transmission parameter from susceptibility to a disease of the proposed epidemic model. The proposed method is a chaos free finite difference scheme, which also preserves the positivity of the solution of the given epidemic model.

Parkinson's pain is more aching and interfering with social life in Caucasians compared to Indians.

Objectives: Although there have been numerous studies conducted to better understand Parkinson's disease (PD), the epidemiology of its debilitating non-motor symptoms across different ethnicities remains understudied. Herein we explore the relationship between depression, anxiety and pain in PD patients of Caucasian or Indian ethnicity (PD Caucasians and PD Indians). Patients and Methods: All patients and healthy age and gender matched controls were assessed via semi-structured interviews for anxiety, pain and depression using structured questionnaires. Results: PD Indians did not differ from PD Caucasians on anxiety or depression. However, PD Caucasians were more likely to report aching pain by 80 times and dull pain by 108 times compared to PD Indians. PD Indians were 82% less likely to have pain interfering with social activities, and 90% less likely to have pain interfering with relations with others compared to PD Caucasians. Conclusion: Although an Indo-Caucasian difference may not be detected from mood dysfunction, important differences may exist from the influence of pain interfering with several dimensions of life.

A new indanedione derivative alleviates symptoms of diabetes by modulating RAGE-NF-kappaB pathway in db/db mice.

Accumulating evidence indicates that a number of tissues are damaged due to build-up of abnormal amount of Advanced Glycation End products (AGEs) in several diseases including diabetes. Currently AGE inhibitors are scarce in clinical use indicating a need for development of new anti-AGE agents. The aim of the current study is to identify the new AGE inhibitors and to decipher their mechanism of action for alleviating symptoms of diabetes in mice. Among several derivatives, one of the derivatives of indanedione, IDD-24 demonstrated highest inhibition of AGE formation and AGE mediated reactive oxygen species production in HepG-2 and mature 3T3-L1 adipocytes. In mice treated with IDD-24, reduction in serum AGE formation and expression of Receptor for AGEs (RAGE) was seen in IDD-24 treated db/db mice. In vivo, glycogen synthesis was also increased in muscle tissue. In adipocytes, anti-AGE agent restored AGEs' induced diminished glucose uptake in fat cells. Mice treated with IDD-24 exhibited increased glucose tolerance, increaed serum adiponectin levels and decreased insulin resistance. Deciphering mechanism of IDD-24 in diabetic mice, it was observed that nuclear factor-κB (NF-κB) and serine phosphorylation of Insulin receptor substrate-1 (IRS-1) declined, while diminished activation of c-Jun NH2-terminal kinase (JNK) appears to be partly responsible for restoration of insulin signaling. We conclude that IDD-24 can be a possible treatment target to address symptoms of diabetes.

Protective effects of Nano-elemental selenium against chromium-vi-induced oxidative stress in broiler liver.

The valuable role of selenium in mitigation of oxidative stress and heavy metal toxicity is well-known. Thus, the aim of the current study on broiler chickens was to examine whether nano elemental selenium (Nano-Se) supplementation can reduce the effects of chromium VI (K2Cr2O7) toxicity. For this purpose, a total of 150, one-day-old broiler chickens were allotted to five groups with three replicates: control group (standard diet), poisoned group (K2Cr2O7 via drinking water), protection group (K2Cr2O7 + Nano- Se), cure group (K2Cr2O7 for initial 2 weeks and then Nano-Se), and prevention group (opposite to the cure group). The broilers were detected by the activities of marker enzymes and oxidative stress markers including, aspartate aminotransferase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT) and superoxide dismutase (SOD), glutathione peroxidase (GSH-px), malondialdehyde (MDA), respectively. The (K2Cr2O7 administration caused histopathological damage in the liver of the chickens. Moreover, changes in serum biochemical indicators and oxidative stress parameters were also observed. Nano-Se supplementation increased the levels of GSH-px but reduced the activities of SOD, MDA, GGT, ALT and AST in the experimental groups (P less than 0.05). Our results showed that Nano-Se plays a protective role by preventing the oxidative stress induced by the chromium VI in broiler chickens.

FK228 recovers thiram-induced tibial dyschondroplasia in chicken via hypoxia inducible factor-1α.

Tibial dyschondroplasia (TD) is a disease of many avian species characterized by an enlarged and avascular lesion in the proximal tibiotarsal bone. The aim of present study was to evaluate the effects of hypoxia-inducible factor-1α(HIF-1α) inhibition on thiram- induced TD using synthetic medicine FK228 and the association between HIF-1α and heat-shock protein 90 (Hsp90). One hundred and fifty broiler chicks were equally divided into 3 groups: control; thiram fed; and FK228 treatment. Expressions of HIF-1α and Hsp90 genes were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR) on day 10 and 14 post-hatch. Western blot analysis of HIF-1α and Hsp90 gene was performed to measure the protein levels at the end of the experiment. Results showed that HIF-1α and Hsp90 levels were significantly (P less than 0.05) up-regulated in the thiram group as compared to the control group. Meanwhile, FK228 (HIF-1α inhibitor) significantly (P less than 0.05) down- regulated the mRNA and protein levels of HIF-1α and Hsp90, restored the size of growth plate and diminished lameness. In conclusion, HIF-1α and Hsp90 play an important role in the formation of avascular growth plate and there is a direct relationship between HIF-1α and Hsp90 for the progression of TD pathogenesis. Therefore, HIF- 1α may prevent and control TD in broiler chickens.

Role of Non-Active-Site Residue Trp-93 in the Function and Stability of New Delhi Metallo-ß-Lactamase 1.

New Delhi metallo-ß-lactamase-1 (NDM-1) is expressed by various members of Enterobacteriaceae as a defense mechanism to hydrolyze ß-lactam antibiotics. Despite various studies showing the significance of active-site residues in the catalytic mechanism, there is a paucity of reports addressing the role of non-active-site residues in the structure and function of NDM-1. In this study, we investigated the significance of non-active-site residue Trp-93 in the structure and function of NDM-1. We cloned blaNDM-1 from an Enterobacter cloacae clinical strain (EC-15) and introduced the mutation of Trp-93 to Ala (yielding the Trp93Ala mutant) by PCR-based site-directed mutagenesis. Proteins were expressed and purified to homogeneity by affinity chromatography. The MICs of the Trp93Ala mutant were reduced 4- to 8-fold for ampicillin, cefotaxime, ceftazidime, cefoxitin, imipenem, and meropenem. The poor hydrolytic activity of the Trp93Ala mutant was also reflected by its reduced catalytic efficiency. The overall catalytic efficiency of the Trp93Ala mutant was reduced by 40 to 55% (the Km was reduced, while the kcat was similar to that of wild-type NDM-1 [wtNDM-1]). Heat-induced denaturation showed that the ΔGD (o) and Tm of Trp93Ala mutant were reduced by 1.8 kcal/mol and 4.8°C, respectively. Far-UV circular dichroism (CD) analysis showed that the α-helical content of the Trp93Ala mutant was reduced by 2.9%. The decrease in stability and catalytic efficiency of the Trp93Ala mutant was due to the loss of two hydrogen bonds with Ser-63 and Val-73 and hydrophobic interactions with Leu-65, Val-73, Gln-123, and Asp-124. The study provided insight into the role of non-active-site amino acid residues in the hydrolytic mechanism of NDM-1.

Impact of ethnicity on mood disorders in Parkinson's disease.

Anxiety and depression are common in Parkinson's disease (PD) patients, yet their prevalence and severity compared to individuals without PD requires more research. Moreover, it has never been compared across different ethnic groups. The objective of this study was to close that gap in the literature by exploring the caseness and severity of anxiety and depression in PD patients of different ethnicities compared to controls without PD. It was found that caseness and severity of anxiety and depression are higher in individuals with PD compared to controls. Furthermore, the caseness and severity of anxiety and depression do not vary significantly among ethnic groups. Finally, depression caseness was not predicted by age, gender, disease duration, restless legs syndrome prevalence, Hoehn and Yahr (H&Y) score nor Unified Parkinson's disease rating scale part III (UPDRS-III) score. Anxiety caseness was predicted by gender, with females 2.7 times more likely to have anxiety caseness than males. Overall, our study suggests that treatment plans should be individualized based on prevalence and severity of the two conditions in individuals with PD rather than generalize treatment for specific ethnic groups.

Association of restless legs syndrome, pain, and mood disorders in Parkinson's disease.

PURPOSE/AIMS: The objectives of the study were to analyze the association between Parkinson's disease and restless legs syndrome, and to explore the relationship between mood disorder comorbidity (anxiety and depression), pain, and restless legs syndrome. METHODS: This study included 123 Parkinson's disease patients and 123 non-Parkinson's disease patients matched for age and gender, and evaluated for anxiety severity, depression severity, pain severity, pain interference, pain disability, and restless legs syndrome prevalence. This was performed using semi-structured interviews and a neurological examination through the restless legs syndrome diagnostic criteria and the following inventories; Hospital Anxiety and Depression Scale, Brief Pain Inventory, and Pain Disability Index. RESULTS: Parkinson's disease patients had significantly greater anxiety severity, depression severity, pain severity, pain interference, pain disability, and restless legs syndrome prevalence in comparison to controls. In addition, Parkinson's disease patients' comorbid for anxiety and depression had significantly greater pain severity, pain interference, and pain disability, but not RLS prevalence, in comparison to Parkinson's disease only, Parkinson's disease anxiety, and Parkinson's disease depression patients. CONCLUSIONS: Pain interference, pain severity, and pain disability is greater among Parkinson's disease patients with anxiety and depression, in comparison to Parkinson's disease patients without anxiety and depression. On the contrary, the prevalence of restless legs syndrome was not found to be relevant.