Geranylgeranoic acid (GGA) originally was identified in some animals and has been developed as an agent for preventing second primary hepatoma. We previously have also identified GGA as an acyclic diterpenoid in some medicinal herbs. Recently, we reported that in human hepatoma-derived HuH-7 cells, GGA is metabolically labeled from ¹³C-mevalonate. Several cell-free experiments have demonstrated that GGA is synthesized through geranylgeranial by oxygen-dependent oxidation of geranylgeraniol (GGOH), but the exact biochemical events giving rise to GGA in hepatoma cells remain unclear. Monoamine oxidase B (MOAB) has been suggested to be involved in GGOH oxidation. Here, using two human hepatoma cell lines, we investigated whether MAOB contributes to GGA biosynthesis. Using either HuH-7 cell lysates or recombinant human MAOB, we found that: 1) the MAO inhibitor tranylcypromine dose-dependently downregulates endogenous GGA levels in HuH-7 cells; and 2) siRNA-mediated MAOB silencing reduces intracellular GGA levels in HuH-7 and Hep3B cells. Unexpectedly, however, CRISPR/Cas9-generated MAOB-KO human hepatoma Hep3B cells had GGA levels similar to those in MAOB-WT cells. A sensitivity of GGA levels to siRNA-mediated MAOB downregulation was recovered when the MAOB-KO cells were transfected with a MAOB-expression plasmid, suggesting that MAOB is the enzyme primarily responsible for GGOH oxidation and that some other latent metabolic pathways may maintain endogenous GGA levels in the MAOB-KO hepatoma cells. Along with the previous findings, these results provide critical insights into the biological roles of human MAOB and provide evidence that hepatic MAOB is involved in endogenous GGA biosynthesis via GGOH oxidation.

Myostatin (or growth/differentiation factor 8 (GDF8)) is a member of the transforming growth factor β superfamily of growth factors and negatively regulates skeletal muscle growth. Its dysregulation is implicated in muscle wasting diseases. SRK-015 is a clinical-stage mAb that prevents extracellular proteolytic activation of pro- and latent myostatin. Here we used integrated structural and biochemical approaches to elucidate the molecular mechanism of antibody-mediated neutralization of pro-myostatin activation. The crystal structure of pro-myostatin in complex with 29H4-16 Fab, a high-affinity variant of SRK-015, at 2.79 Å resolution revealed that the antibody binds to a conformational epitope in the arm region of the prodomain distant from the proteolytic cleavage sites. This epitope is highly sequence-divergent, having only limited similarity to other closely related members of the transforming growth factor β superfamily. Hydrogen/deuterium exchange MS experiments indicated that antibody binding induces conformational changes in pro- and latent myostatin that span the arm region, the loops contiguous to the protease cleavage sites, and the latency-associated structural elements. Moreover, negative-stain EM with full-length antibodies disclosed a stable, ring-like antigen–antibody structure in which the two Fab arms of a single antibody occupy the two arm regions of the prodomain in the pro- and latent myostatin homodimers, suggesting a 1:1 (antibody:myostatin homodimer) binding stoichiometry. These results suggest that SRK-015 binding stabilizes the latent conformation and limits the accessibility of protease cleavage sites within the prodomain. These findings shed light on approaches that specifically block the extracellular activation of growth factors by targeting their precursor forms.

Antibodies are widely used as cancer therapeutics, but their current use is limited by the low number of antigens restricted to cancer cells. A receptor tyrosine kinase, receptor tyrosine kinase-like orphan receptor 2 (ROR2), is normally expressed only during embryogenesis and is tightly down-regulated in postnatal healthy tissues. However, it is up-regulated in a diverse set of hematologic and solid malignancies, thus ROR2 represents a candidate antigen for antibody-based cancer therapy. Here we describe the affinity maturation and humanization of a rabbit mAb that binds human and mouse ROR2 but not human ROR1 or other human cell-surface antigens. Co-crystallization of the parental rabbit mAb in complex with the human ROR2 kringle domain (hROR2-Kr) guided affinity maturation by heavy-chain complementarity-determining region 3 (HCDR3)-focused mutagenesis and selection. The affinity-matured rabbit mAb was then humanized by complementarity-determining region (CDR) grafting and framework fine tuning and again co-crystallized with hROR2-Kr. We show that the affinity-matured and humanized mAb retains strong affinity and specificity to ROR2 and, following conversion to a T cell–engaging bispecific antibody, has potent cytotoxicity toward ROR2-expressing cells. We anticipate that this humanized affinity-matured mAb will find application for antibody-based cancer therapy of ROR2-expressing neoplasms.

We reviewed ¹¹¹In-DOTA-anti-CD45 antibody (BC8) imaging and bone marrow biopsy measurements to ascertain biodistribution and biokinetics of the radiolabeled antibody and to investigate differences based on type of hematologic malignancy. Methods: Serial whole-body scintigraphic images (4 time-points) were obtained after infusion of the ¹¹¹In-DOTA-BC8 (176-406 MBq) in 52 adult patients with hematologic malignancies (lymphoma, multiple myeloma, acute myeloid leukemia and myelodysplastic syndrome). Counts were obtained for the regions of interest for spleen, liver, kidneys, testicles (in males), and two marrow sites (acetabulum and sacrum) and correction for attenuation and background was made. Bone marrow biopsies were obtained 14-24 hours post-infusion and percent of administered activity was determined. Radiation absorbed doses were calculated. Results: Initial uptake in liver averaged 32% ± 8.4% (S.D.) of administered activity (52 patients), which cleared monoexponentially with biological half-time of 293 ± 157 hours (33 patients) or did not clear (19 patients). Initial uptake in spleen averaged 22% ± 12% and cleared with a biological half-time 271 ± 185 hours (36 patients) or longer (6 patients). Initial uptake in kidney averaged 2.4% ± 2.0% and cleared with a biological half-time of 243 ± 144 hours (27 patients) or longer (9 patients). Initial uptake in red marrow averaged 23% ± 11% and cleared with half-times of 215 ± 107 hours (43 patients) or longer (5 patients). Whole-body retention half-times averaged 198 ± 75 hours. Splenic uptake was higher in the AML/MDS group when compared to the lymphoma group (p ≤ 0.05) and to the multiple myeloma group (p ≤ 0.10). Liver represented the dose-limiting organ. For liver uptake, no significant differences were observed between the three malignancy groups. Average calculated radiation absorbed doses per unit administered activity for a therapy infusions of ⁹⁰Y-DOTA-BC8 were for red marrow: 470 ± 260 cGy/MBq, liver 1100 ± 330 cGy/MBq, spleen 4120 ± 1950 cGy/MBq, total body 7520 ± 20 cGy/MBq, osteogenic cells 290 ± 200 cGy/MBq, and kidneys 240 ± 200 cGy/MBqR. Conclusion: ¹¹¹In-DOTA-BC8 had long retention time in liver, spleen, kidneys, and red marrow, and the highest absorbed doses were calculated for spleen and liver. Few differences were observed by malignancy type. The exception was greater splenic uptake among leukemia/MDS group when compared to lymphoma and multiple myeloma groups.

The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer (PCa). However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 biochemically recurrent PCa patients. Each subject served as his own control. [¹⁸F]DCFPyl PET/CT imaging sessions were performed 3 – 7 days apart, following oral administration of either 12.7 g of MSG or placebo. Data from the two sets of images were analyzed by placing regions of interest on lacrimal, parotid and submandibular glands, left ventricle, liver, spleen, kidneys, bowel, urinary bladder, gluteus muscle and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the ROI data. Results: A total of 142 pathological lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in maximal standardized uptake values corrected for lean body mass (SULmax) on images obtained following MSG administration in the parotids (24 ± 14%, P = 0.001), submandibular glands (35 ± 11%, P<0.001) and kidneys (23 ± 26%, P = 0.014). Significant decreases were also observed in lacrimal glands (49 ± 13%, P<0.001), liver (15 ± 6%, P<0.001), spleen (28 ± 13%, P = 0.001) and bowel (44 ± 13%, P<0.001). Mildly lower blood pool SULmean was observed after MSG administration (decrease of 11 ± 13%, P = 0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration compared to the placebo studies (SULmax median decrease 33%, range -1 to 75%, P<0.001). No significant adverse events occurred and vital signs were stable following placebo or MSG administration. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney and other normal organ PSMA radiotracer uptake in human subjects, using [¹⁸F]DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications.

FcRIIIa (CD16a) and FcRIIa (CD32a) on monocytes are essential for proper effector functions including antibody dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). Indeed, therapeutic monoclonal antibodies (mAbs) that bind FcRs with greater affinity exhibit greater efficacy. Furthermore, post-translational modification impacts antibody binding affinity, most notably the composition of the asparagine(N)-linked glycan at N162 of CD16a. CD16a is widely recognized as the key receptor for the monocyte response, however the post-translational modifications of CD16a from endogenous monocytes are not described. Here we isolated monocytes from individual donors and characterized the composition of CD16a and CD32a N-glycans from all modified sites. The composition of CD16a N-glycans varied by glycosylation site and donor. CD16a displayed primarily complex-type biantennary N-glycans at N162, however some individuals expressed CD16a V158 with ~20% hybrid and oligomannose types which increased affinity for IgG1 Fc according to surface plasmon resonance binding analyses. The CD16a N45-glycans contain markedly less processing than other sites with >75% hybrid and oligomannose forms. N38 and N74 of CD16a both contain highly processed complex-type N-glycans with N-acetyllactosamine repeats and complex-type biantennary N-glycans dominate at N169. The composition of CD16a N-glycans isolated from monocytes included a higher proportion of oligomannose-type N-glycans at N45 and less sialylation plus greater branch fucosylation than we observed in a recent analysis of NK cell CD16a. The additional analysis of CD32a from monocytes revealed different features than observed for CD16a including the presence of a predominantly biantennary complex-type N-glycans with two sialic acids at both sites (N64 and N145).

Gernot F. Grabner
Apr 29, 2020; 0:jlr.RA119000516v1-jlr.RA119000516
Research Articles

Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid (LBPA), is a phospholipid that promotes lipid sorting in late endosomes/lysosomes by activating lipid hydrolases and lipid transfer proteins. Changes in the cellular BMP content therefore reflect an altered metabolic activity of the endo-lysosomal system. Surprisingly, little is known about the physiological regulation of BMP. In this study, we investigated the effects of nutritional and metabolic factors on BMP profiles of whole tissues and  parenchymal and non-parenchymal cells. Tissue samples were obtained from fed, fasted, two-hours refed, and insulin-treated mice, as well as from mice housed at  5°C, 22°C, or 30°C. These tissues exhibited distinct BMP profiles, which were regulated by the nutritional state in a tissue-specific manner. Insulin treatment was not sufficient to mimic refeeding-induced changes in tissue BMP levels indicating that BMP metabolism is regulated by other hormonal or nutritional factors. Tissue fractionation experiments revealed that fasting drastically elevates BMP levels in hepatocytes and pancreatic cells. Furthermore, we observed that the BMP content in brown adipose tissue strongly depends on housing temperatures. In conclusion, our observations suggest that BMP concentrations adapt to the metabolic state in a tissue-and cell type-specific manner in mice. Drastic changes observed in hepatocytes, pancreatic cells, and brown adipocytes suggest that BMP possesses a role in the functional adaption to nutrient starvation and ambient temperature.

Geranylgeranoic acid (GGA) originally was identified in some animals and has been developed as an agent for preventing second primary hepatoma. We previously have also identified GGA as an acyclic diterpenoid in some medicinal herbs. Recently, we reported that in human hepatoma-derived HuH-7 cells, GGA is metabolically labeled from ¹³C-mevalonate. Several cell-free experiments have demonstrated that GGA is synthesized through geranylgeranial by oxygen-dependent oxidation of geranylgeraniol (GGOH), but the exact biochemical events giving rise to GGA in hepatoma cells remain unclear. Monoamine oxidase B (MOAB) has been suggested to be involved in GGOH oxidation. Here, using two human hepatoma cell lines, we investigated whether MAOB contributes to GGA biosynthesis. Using either HuH-7 cell lysates or recombinant human MAOB, we found that: 1) the MAO inhibitor tranylcypromine dose-dependently downregulates endogenous GGA levels in HuH-7 cells; and 2) siRNA-mediated MAOB silencing reduces intracellular GGA levels in HuH-7 and Hep3B cells. Unexpectedly, however, CRISPR/Cas9-generated MAOB-KO human hepatoma Hep3B cells had GGA levels similar to those in MAOB-WT cells. A sensitivity of GGA levels to siRNA-mediated MAOB downregulation was recovered when the MAOB-KO cells were transfected with a MAOB-expression plasmid, suggesting that MAOB is the enzyme primarily responsible for GGOH oxidation and that some other latent metabolic pathways may maintain endogenous GGA levels in the MAOB-KO hepatoma cells. Along with the previous findings, these results provide critical insights into the biological roles of human MAOB and provide evidence that hepatic MAOB is involved in endogenous GGA biosynthesis via GGOH oxidation.

Myostatin (or growth/differentiation factor 8 (GDF8)) is a member of the transforming growth factor β superfamily of growth factors and negatively regulates skeletal muscle growth. Its dysregulation is implicated in muscle wasting diseases. SRK-015 is a clinical-stage mAb that prevents extracellular proteolytic activation of pro- and latent myostatin. Here we used integrated structural and biochemical approaches to elucidate the molecular mechanism of antibody-mediated neutralization of pro-myostatin activation. The crystal structure of pro-myostatin in complex with 29H4-16 Fab, a high-affinity variant of SRK-015, at 2.79 Å resolution revealed that the antibody binds to a conformational epitope in the arm region of the prodomain distant from the proteolytic cleavage sites. This epitope is highly sequence-divergent, having only limited similarity to other closely related members of the transforming growth factor β superfamily. Hydrogen/deuterium exchange MS experiments indicated that antibody binding induces conformational changes in pro- and latent myostatin that span the arm region, the loops contiguous to the protease cleavage sites, and the latency-associated structural elements. Moreover, negative-stain EM with full-length antibodies disclosed a stable, ring-like antigen–antibody structure in which the two Fab arms of a single antibody occupy the two arm regions of the prodomain in the pro- and latent myostatin homodimers, suggesting a 1:1 (antibody:myostatin homodimer) binding stoichiometry. These results suggest that SRK-015 binding stabilizes the latent conformation and limits the accessibility of protease cleavage sites within the prodomain. These findings shed light on approaches that specifically block the extracellular activation of growth factors by targeting their precursor forms.

Antibodies are widely used as cancer therapeutics, but their current use is limited by the low number of antigens restricted to cancer cells. A receptor tyrosine kinase, receptor tyrosine kinase-like orphan receptor 2 (ROR2), is normally expressed only during embryogenesis and is tightly down-regulated in postnatal healthy tissues. However, it is up-regulated in a diverse set of hematologic and solid malignancies, thus ROR2 represents a candidate antigen for antibody-based cancer therapy. Here we describe the affinity maturation and humanization of a rabbit mAb that binds human and mouse ROR2 but not human ROR1 or other human cell-surface antigens. Co-crystallization of the parental rabbit mAb in complex with the human ROR2 kringle domain (hROR2-Kr) guided affinity maturation by heavy-chain complementarity-determining region 3 (HCDR3)-focused mutagenesis and selection. The affinity-matured rabbit mAb was then humanized by complementarity-determining region (CDR) grafting and framework fine tuning and again co-crystallized with hROR2-Kr. We show that the affinity-matured and humanized mAb retains strong affinity and specificity to ROR2 and, following conversion to a T cell–engaging bispecific antibody, has potent cytotoxicity toward ROR2-expressing cells. We anticipate that this humanized affinity-matured mAb will find application for antibody-based cancer therapy of ROR2-expressing neoplasms.

Tina Vilsbøll
Jun 1, 2007; 30:1608-1610
BR Emerging Treatments and Technologies

Vanita R. Aroda
Sep 1, 2019; 42:1724-1732
Emerging Therapies: Drugs and Regimens

I was recently invited to write a book chapter on nonmonogamy in LGBTQ+ relationships, and one of the things I wanted to do in it was compare the prevalence of both consensual nonmonogamy (polyamory, open relationships, swinging) and nonconsensual nonmonogamy (cheating/infidelity). Further, I wanted to look at whether rates of these practices were similar or different for LGBTQ+ persons compared to heterosexual persons. However, I found it surprisingly difficult to locate reliable data points. The problem I kept running into is that study after study conflated consensual nonmonogamy with nonconsensual nonmonogamy. In other words, researchers were putting all of these folks into the same category without attempting to distinguish whether they were permitted under the rules of the relationship or not.

Erlangen : F. Enke, 1850.

Leipzig : Duncker & Humblot, 1868.

Berlin : A. Hirschwald, 1864.

Berlin : A. Hirschwald, 1877.

Basel : Schwabe, 1886.

Berlin : Hirschwald, 1887.

Leipzig : W. Engelmann, 1862.

Berlin : A. Hirschwald, 1895.

Berlin : Hirschwald, 1876.

Leipzig : F. Deuticke, 1895.

Stuttgart : F. Enke, 1879.

Leipzig : T.O. Weigel, 1859.

Alexandre Mösching, Lutz Dümbgen.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 24--49.

Abstract:
We consider bivariate observations $(X_{1},Y_{1}),ldots,(X_{n},Y_{n})$ such that, conditional on the $X_{i}$, the $Y_{i}$ are independent random variables. Precisely, the conditional distribution function of $Y_{i}$ equals $F_{X_{i}}$, where $(F_{x})_{x}$ is an unknown family of distribution functions. Under the sole assumption that $xmapsto F_{x}$ is isotonic with respect to stochastic order, one can estimate $(F_{x})_{x}$ in two ways: (i) For any fixed $y$ one estimates the antitonic function $xmapsto F_{x}(y)$ via nonparametric monotone least squares, replacing the responses $Y_{i}$ with the indicators $1_{[Y_{i}le y]}$. (ii) For any fixed $eta in (0,1)$ one estimates the isotonic quantile function $xmapsto F_{x}^{-1}(eta)$ via a nonparametric version of regression quantiles. We show that these two approaches are closely related, with (i) being more flexible than (ii). Then, under mild regularity conditions, we establish rates of convergence for the resulting estimators $hat{F}_{x}(y)$ and $hat{F}_{x}^{-1}(eta)$, uniformly over $(x,y)$ and $(x,eta)$ in certain rectangles as well as uniformly in $y$ or $eta$ for a fixed $x$.

Kentaro Minami.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 1508--1576.

Abstract:
We study the problem of estimating piecewise monotone vectors. This problem can be seen as a generalization of the isotonic regression that allows a small number of order-violating changepoints. We focus mainly on the performance of the nearly-isotonic regression proposed by Tibshirani et al. (2011). We derive risk bounds for the nearly-isotonic regression estimators that are adaptive to piecewise monotone signals. The estimator achieves a near minimax convergence rate over certain classes of piecewise monotone signals under a weak assumption. Furthermore, we present an algorithm that can be applied to the nearly-isotonic type estimators on general weighted graphs. The simulation results suggest that the nearly-isotonic regression performs as well as the ideal estimator that knows the true positions of changepoints.

Natalia Shenkman.

Source: Brazilian Journal of Probability and Statistics, Volume 34, Number 1, 127--135.

Abstract:
While derivations of the characterization of the $d$-variate exchangeable Marshall–Olkin copula via $d$-monotone sequences relying on basic knowledge in probability theory exist in the literature, they contain a myriad of unnecessary relatively complicated computations. We revisit this issue and provide proofs where all undesired artefacts are removed, thereby exposing the simplicity of the characterization. In particular, we give an insightful analytical derivation of the monotonicity conditions based on the monotonicity properties of the survival probabilities.

Achillefs Tzioufas.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 3, 674--684.

Abstract:
The epidemic process on a graph is considered for which infectious contacts occur at rate which depends on whether a susceptible is infected for the first time or not. We show that the Vasershtein coupling extends if and only if secondary infections occur at rate which is greater than that of initial ones. Nonetheless we show that, with respect to the probability of occurrence of an infinite epidemic, the said proviso may be dropped regarding the totally asymmetric process in one dimension, thus settling in the affirmative this special case of the conjecture for arbitrary graphs due to [ Ann. Appl. Probab. 13 (2003) 669–690].

Davide Gabrielli, Ida Germana Minelli.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 3, 558--585.

Abstract:
Stochastic monotonicity is a well-known partial order relation between probability measures defined on the same partially ordered set. Strassen theorem establishes equivalence between stochastic monotonicity and the existence of a coupling compatible with respect to the partial order. We consider the case of a countable set and introduce the class of finitely decomposable flows on a directed acyclic graph associated to the partial order. We show that a probability measure stochastically dominates another probability measure if and only if there exists a finitely decomposable flow having divergence given by the difference of the two measures. We illustrate the result with some examples.

Solveig Engebretsen, Ingrid K. Glad.

Source: Statistics Surveys, Volume 13, 1--51.

Abstract:
In numerous problems where the aim is to estimate the effect of a predictor variable on a response, one can assume a monotone relationship. For example, dose-effect models in medicine are of this type. In a multiple regression setting, additive monotone regression models assume that each predictor has a monotone effect on the response. In this paper, we present an overview and comparison of very recent frequentist methods for fitting additive monotone regression models. Three of the methods we present can be used both in the high dimensional setting, where the number of parameters $p$ exceeds the number of observations $n$, and in the classical multiple setting where $1<pleq n$. However, many of the most recent methods only apply to the classical setting. The methods are compared through simulation experiments in terms of efficiency, prediction error and variable selection properties in both settings, and they are applied to the Boston housing data. We conclude with some recommendations on when the various methods perform best.

Dopaminergic neurons innervate extensive areas of the brain and release dopamine (DA) onto a wide range of target neurons. However, DA release is also precisely regulated. In Drosophila melanogaster brain explant preparations, DA is released specifically onto α3/α'3 compartments of mushroom body (MB) neurons that have been coincidentally activated by cholinergic and glutamatergic inputs. The mechanism for this precise release has been unclear. Here we found that coincidentally activated MB neurons generate carbon monoxide (CO), which functions as a retrograde signal evoking local DA release from presynaptic terminals. CO production depends on activity of heme oxygenase in postsynaptic MB neurons, and CO-evoked DA release requires Ca²⁺ efflux through ryanodine receptors in DA terminals. CO is only produced in MB areas receiving coincident activation, and removal of CO using scavengers blocks DA release. We propose that DA neurons use two distinct modes of transmission to produce global and local DA signaling.

SIGNIFICANCE STATEMENT Dopamine (DA) is needed for various higher brain functions, including memory formation. However, DA neurons form extensive synaptic connections, while memory formation requires highly specific and localized DA release. Here we identify a mechanism through which DA release from presynaptic terminals is controlled by postsynaptic activity. Postsynaptic neurons activated by cholinergic and glutamatergic inputs generate carbon monoxide, which acts as a retrograde messenger inducing presynaptic DA release. Released DA is required for memory-associated plasticity. Our work identifies a novel mechanism that restricts DA release to the specific postsynaptic sites that require DA during memory formation.

1. Bharat Biotech to lead human monoclonal antibodies project  The Hindu
2. Bharat Biotech leads CSIR project to develop antibodies against Covid-19  Times of India
3. Bharat Biotech To Lead CSIR’s Project To Develop Human Monoclonal Antibodies For Covid-19 Therapy  Swarajya
4. Bharat Biotech to develop human antibodies for COVID-19 therapy  Telangana Today
5. Bharat Biotech vows human monoclonal antibodies to neutralise COVID-19 in 6 months  Mumbai Mirror
6. View Full coverage on Google News

Nearly one-third of all US children are overweight or obese, with even higher prevalence among Mexican American children. Overweight and obesity increase systemic inflammation, contributing to increased risk for chronic diseases, such as type 2 diabetes mellitus and cardiovascular disease.

Obese Mexican American children had concurrent alterations in both inflammatory markers and traditional disease risk markers, relative to healthy weight children. Our results provide evidence partially explaining the health disparity for disease in Mexican American children who are overweight/obese. (Read the full article)

Children with Lyme and septic arthritis of the knee may present similarly, although septic arthritis requires prompt treatment initiation to avoid joint destruction. Clinicians must make initial management decisions without Lyme serology and bacterial culture results.

Our clinical prediction rule accurately identified patients at low risk for septic arthritis in a Lyme disease–endemic area. In the appropriate clinical context, low-risk patients may be spared invasive testing such as diagnostic arthrocentesis. (Read the full article)

Antibiotics-induced rash in Epstein-Barr virus acute infectious mononucleosis, especially the aminopenicillins-induced type, was first described during the 1960s, with a reported incidence of 80% to 100%. This phenomenon was not further investigated but is well-established in pediatric textbooks.

The main observation of this study is that rash induced by amoxicillin in confirmed Epstein-Barr virus acute infectious mononucleosis was found at a rate of ~30%, which is much lower than previously reported. (Read the full article)

Monovalent rotavirus vaccine was introduced for infants in the United States in 2008. Previous US evaluations have not specifically assessed the performance of this vaccine under routine use.

Using the same methodology and covering the same time period, high effectiveness (~90%) was demonstrated for the monovalent and the pentavalent rotavirus vaccine series against rotavirus disease resulting in emergency department/inpatient care, in children up to 2 years of age. (Read the full article)

Three years after the launch of the M10, Leica is bringing a black-and-white Monochrom version to market, with an all-new 40MP imager and the classic M rangefinder design.

The IMpact-RSV Study Group
Sep 1, 1998; 102:531-537
ARTICLES

Penn State Beaver students will give a special performance of Eve Ensler’s "The Vagina Monologues" at 5 p.m. Feb. 13 in the Penn State Beaver auditorium. The event is open to the public.

'With no incentive to innovate or invest, these conglomerates charge sky-high internet prices to reap profits from consumers,' the Democratic Presidential candidate said in unveiling his 'high-speed internet access for all plan' on Friday.

Source: www.youtube.com - Wednesday, May 06, 2020

"What mothers really want for mother's day but can't tell their kids," wrote Twinkle

This project brings together National Centre for Cell Science (NCCS), Pune; Indian Institute of Technology, Indore, and Gurgaon-based PredOmix Technologies in a collaborative mode for a public health emergency.

1. Bharat Biotech to lead human monoclonal antibodies venture  Microbioz India
2. Bharat Biotech to lead monoclonal antibodies project for Covid-19 therapy  The Financial Express
3. Bharat Biotech leads CSIR project to develop antibodies against Covid-19  Times of India
4. CSIR approves project to develop human monoclonal antibodies that can neutralize COVID-19 in patients  Times Now
5. Bharat Biotech to lead project on monoclonal antibodies therapy for COVID-19  The New Indian Express
6. View Full coverage on Google News

New York State is pushing its utility industry to shift away from a century-old business model into a system that can accommodate more power from solar and wind.