The sarcoid-like reaction is a rare autoinflammatory disease that can affect lymph nodes or organs but does not meet the diagnostic criteria for systemic sarcoidosis. Several drug classes have been associated with the development of a systemic sarcoid-like reaction, which defines drug-induced sarcoidosis-like reactions and can affect a single organ. Anti-CD20 antibodies (rituximab) have rarely been reported as responsible for this reaction and this adverse effect has mainly been described during the treatment of Hodgkin’s lymphoma. We report a unique case of a sarcoid-like reaction complicating rituximab following the treatment of a mantle cell lymphoma and interesting only the kidney. The 60-year-old patient presented with severe acute renal failure six months after the end of his r-CHOP protocol and the urgent renal biopsy revealed acute interstitial nephritis rich in granulomas without caseous necrosis. After ruling out other causes of granulomatous nephritis, a sarcoid-like reaction was retained since infiltration was limited to the kidney. The temporal relationship between rituximab administration and the sarcoid-like reaction onset in our patient supported the diagnosis of a rituximab-induced sarcoidosis-like reaction. Oral corticosteroid treatment led to rapid and lasting improvement in renal function. Clinicians should be warned of this adverse effect and regular and prolonged monitoring of renal function should be recommended during the follow-up of patients after the end of treatment with rituximab.

Aims: The serratus anterior plane block (SAPB) has commonly been utilized as a regional anesthesia technique for pain management in various upper chest surgical procedures. The purpose of this study was to investigate the analgesic effect and pharmacokinetics of ropivacaine in continuous SAPB undergoing VATS. Methods: This prospective randomized study included patients scheduled for elective VATS. Patients first received a bolus of 20 ml of 0.2% (Group L) or 0.375% (Group H) ropivacaine that was administered beneath the serratus anterior muscle. The pump was connected to the catheter for continuous administration within 48 hours postoperatively, in which a background infusion at a rate of 7 ml·h−1 of low-dose at 0.2% (Group L) or high-dose at 0.375% (Group H) of ropivacaine was administered. The main results were to compare the analgesic effects and analyze the pharmacokinetics of different concentrations of ropivacaine. Results: Eighty-eight patients agreed to participate in the trial and were recruited. The VAS scores in Group H at 12, 24, and 48 hours postoperatively at rest and on coughing were significantly lower than those in Group L. The peak values of total ropivacaine plasma concentrations were observed at 48 hours (2.01 μg·mL−1 for Group L and 2.93 μg·mL−1 for Group H), which were far below the theoretical toxicity threshold. Postoperative rescue analgesia, complications, and other outcomes did not differ significantly. Conclusions: In VATS patients, the analgesic effect of 0.2% ropivacaine for continuous SAPB was not inferior to that of 0.375% ropivacaine, and the blood concentration of 0.2% ropivacaine was

AbstractFabrication of structures in unstructured environments is a promising field to expand the application spaces of additive manufacturing (AM). One potential application is to add new components directly onto existing structures. In this paper, we developed a versatile, reconfigurable direct ink write (DIW) manufacturing method in tandem with a two-stage hybrid ink designed to fabricate high-strength, self-supporting parts in unconventional printing spaces, such as underneath a build surface or horizontally. Our two-stage hybrid DIW ink combines a photopolymer and a tough epoxy resin. The photopolymer can be cured rapidly to enable layer-by-layer printing complex structures. It also possesses adequate adhesion to allow the fabrication of large volume structures on a diversity of substrates including acrylic, wood, glass, aluminum, and concrete. The epoxy component can be cured after 72 hours in ambient conditions with further increased adhesion strengths. We demonstrated the capabilities of the reconfigurable DIW extrusion nozzle method to print complex structures in inverted and horizontal environments. Finally, via the addition of DIW-deposited conductive paths, we created a functional 3D printed structure capable of in-situ deformation monitoring. This work has the potential to be used for applications such as appending new parts to existing structures for increasing functionality, repair, and structure health monitoring.Corresponding author: H. Jerry Qi, qih@me.gatech.edu

Introduction: Rituximab, which is widely used in the treatment of B-cell lymphoma, is a chimeric monoclonal antibody directed against the CD20 antigen. Rituximab has many side effects, mainly allergic and neurological. Rituximab may cause thrombocytopenia in the long term after administration. Rare cases with rituximab-induced acute thrombocytopenia have been reported in the literature. Case Report: A 51-year-old female patient who newly diagnosed splenic marginal zone lymphoma recieved rituximab as first line therapy. Petechiae occurred in the lower extremities on the day following rituximab administration. The blood test showed a severe drop in the platelet count from 112,000/μL to 5,000/μL. Blood peripheral smear evaluation confirmed severe thrombocytopenia. Management and outcome: There was no change in hemoglobin or white blood cell levels. After the diagnosis of rituximab-induced acute thrombocytopenia, thrombocyte suspension was administered due to the risk of bleeding. Close clinical and laboratory observations were made. The platelet count began to rise gradually in the following period. Before the second week of rituximab administration, the platelet count was 122,000/μL. No complications developed after premedication and slow rituximab administration, and subsequent treatments were continued in the same way. Discussion: Rituximab has a widespread use, especially in malignancies and autoimmune diseases. Like many monoclonal antibodies, rituximab has several side effects. Thrombocytopenia is a long-term side effect associated with rituximab, and rituximab-induced severe acute thrombocytopenia has been rarely reported. Therefore, it should be kept in mind that severe acute thrombocytopenia may develop after rituximab administration.

Background: Diabetes prior to conception may cause pregnancy complications through disruptions of placental function. Objectives/Key Questions: 1) To describe placental changes in women with pre-existing diabetes. 2) To determine if elastography can detect in-vivo placental changes? Search Strategy: PubMed, Embase, Medline, Cochrane database searches of English language reports published until July 2020. Selection Criteria: Question 1: Any study describing placental histopathology in women with known diabetes. Question 2: Any study using elastography to report in-vivo placental stiffness values. Data Collection and Analysis: For Key Question 1: we grouped placental pathologies using Amsterdam International Consensus Group definitions. For Key Question 2: we conducted a meta-analysis of placental stiffness scores reported in metres per second (m/s) or kilopascals (kPa). Main Results: Cumulative data from 14 studies showed no placental histopathology features pathognomonic for diabetes. Pooled analysis of 14 studies included 478 “high risk pregnancies” and 828 control/healthy pregnancies. Only one study reported stiffness scores for placentas of women with pre-existing diabetes (N < 10 women). Maternal-derived pathologies resulted in higher placental stiffness with mean difference 4.5kPa (95% CI 3.16, 5.87) compared to control / healthy pregnancies. Fetal-derived pathologies resulted in higher placental stiffness with mean difference of 6.5kPa (95% CI 1.08, 11.86) compared to control / healthy pregnancies. Conclusions: Shear Wave Elastography may provide in-vivo approximation of placental histopathology. Further studies in women with pre-existing diabetes may confirm this. Funding: primary author (AG) receives Western Sydney University Postgraduate Research Scholarship (Ainsworth Trust) and Australian Federal Government Research Training Program (RTP) Fees Offset.

Background and Purpose: Although the prevalence of nonalcoholic steatohepatitis (NASH) is rapidly increasing, effective therapy is lacking. Tenofovir alafenamide (TAF) is a widely used antiviral drug for hepatitis B. In this study, we investigated the potential pharmacological effects of TAF on NASH. Experimental Approach: Two different NASH mouse models were established: 1) by subcutaneous injection of streptozotocin (0.2 mg) and feeding the mice a high-fat, high-cholesterol (HFHC) diet, and 2) feeding the mice a choline-deficient, L-amino acid-defined, high-fat (CDAHF) diet. Key Results: Serum alanine aminotransferase and triglyceride levels in TAF-treated NASH mice were significantly lower than those in the mock-treated ones. The livers from the TAF-treated NASH mice showed attenuated mononuclear phagocyte (MP) infiltration compared to those from the mock-treated ones. TAF-treated NASH mice exhibited decreased liver infiltration of activated MPs (IAIE+/PD-L1+/MerTK+). In ex vivo experiments using sorted human CD14+ monocytes treated with lipopolysaccharide (LPS) and/or TAF, we confirmed the decreased level of phosphorylated AKT in TAF-treated LPS-stimulated monocytes compared to that in the mock-treated ones. Mouse liver immunoblotting showed that phosphorylation levels of AKT were significantly lower in the TAF-treated NASH group than in the mock-treated group. Conclusion and Implications: TAF exerts anti-inflammatory effects in NASH livers by attenuating AKT phosphorylation in intrahepatic activated MPs. Therefore, TAF may serve as a new therapeutic option for NASH.

Sistemas de correntes e rodas dentadas são um dos principais tipos de elementos de transmissão de potência mecânica flexível. Apesar de ser um sistema clássico, na atualidade graças a sua padronização, desenvolvimento de matérias e precisão de transmissão, esse tipo de elementos mecânicos vem sendo alavancados para aplicações da denominada Agricultura 4.0. No presente trabalho, com o objetivo de apresentar as principais normas, conceitos e recomendações de projeto, que regem nesses sistemas mecânicos, será desenvolvido um estudo de caso, possibilitando ao leitor se familiarizar e aprender a realizar uma escolha correta para um futuro projeto mecânico e/ou uma otimização de manutenção em um equipamento existente, selecionando elementos mecânicos: roda dentara e corrente.

Objective: The study aims to equip the Obstetrician and Gynaecologist with the knowledge of clinical conditions that will benefit from interventional radiology, the equipment and materials that are commonly used the benefits and the complications and side effects of these techniques. Design :A single centre, retrospective cohort study Population. All obstetric and gynecological cases in which interventional radiology techniques were used Methods: Review article with examples from hospital practice from 2015 to 2021 acquired through computerized database Statistical Analysis: No statistical analysis of data was required as it was a single Centre retrospective analysis of cases. Outcome: We had a total of 35 cases, including but not limited to placenta accreta spectrum disorders ,fibroid,pelvic congestion syndrome and arteriovenous malformation ,who underwent various interventional radiological procedures ranging from embolization of uterine artery, peripheral angiography and embolization ,internal iliac artery balloon placement to ovarian vein embolization and coil insertion . Conclusion: Increased collaborative efforts between interventional radiology and gynaecology would allow for patients to be fully informed on the complete spectrum of surgical and nonsurgical treatment options available to them. Tweetable abstract: Evolving role of interventional radiology in obstetrics and gynaecology

Objective The present study aimed to explore if bovine parvovirus (BPV) impacts beta interferon (IFN-β) production and to reveal further molecular mechanism of BPV immune escape. Method The pCMV-Myc-BPV-VP1 recombinant plasmid was verified with both double enzyme digestion and sequence. HEK 293T cells were transfected with this recombinant protein, then infected with the vesicular stomatitis virus (VSV). Expression levels of IFN-β mRNA were detected using qPCR. Results Expression level of BPV VP1 mRNA in pCMV-Myc-BPV-VP1 group was significantly higher than those of the untreated group (UT) and pCMV-Myc vector group. BPV virus copies in bovine turbinate (BT) cells of BPV-VP1 group were raised (P<0.05) with an increment of 5.8×104. Expression levels of IFN-β mRNA of BPV VP1 group in HEK 293T cells were decreased (P<0.01). Following treatment of TBK1 and IRF3(5D), IFN-β expression levels in HEK 293T cells were depressed. Expression levels of TBK1, IRF3(5D), MDA5 and MAVS were lower than those of their self treatment. Conclusion pCMV-Myc-BPV-VP1 could heighten transcription levels of VP1 protein in BT cells, promote BPV proliferation and ascend the production of IFN-β. Overexpression of pCMV-Myc-BPV-VP decreased IFN-β mRNA expression in HEK 293T cells and inhibited IFN-β production induced by TBK1 and IRF3(5D). Furthermore, BPV VP1 obviously declined expression levels of TBK1, IRF3(5D), MDA5 and MAVS in RLR pathway. Our findings revealed a new mechanism evolved by BPV VP1 to inhibit type I IFN production and provided a solid basis into the immunosuppression of BPV, which is beneficial for developing novel strategy oftherapy of BPV disease.

We report the case of a massive Nortriptyline and Livergol overdose, presenting with the typical Nortriptyline intoxication features, including QT prolongation and rapid response to the treatment, which provides a rationale for the safety profile of Silymarin medications with minimal risks of drug-drug interactions.

The elliptic obstacle problems with variable exponents and multivalued reaction terms, depending on the gradient, are considered in this paper. Under general assumptions on the convection term, we prove two existence theorems of a (weak) nontrivial solution by using the surjective theorem and the Leray-Schauder fixed point theorem for multivalued mappings, respectively. Our assumptions are suitable and different from those required in the previous literature.

We report a case of TEN probably related to Pristinamycin

Guidelines for the approval or licensing of biosimilars have evolved over the past 18 years since the first introduction of biosimilars. Amendments to these guidelines are constrained in the US by legislation and in the EU and WHO due to collaborative consent requirements. The MHRA has recently joined ICH and brought its guideline that is most rational and scientific; it removes animal and clinical efficacy testing, as evidenced by hundreds of studies, billions of doses administered, and a better understanding of recombinant therapeutic proteins. However, there remains a need to bring a neutral jurisdiction guideline that all countries can adopt; while the EU, FDA, Japan, and now the UK are the deciding countries, they all realize the shortcomings and will be willing to support an ICH guideline, as proposed here. Compliance with a unified ICH guideline will promote the entry of safer biosimilars and cross-country registrations. This review is based on identifying the shortcomings of the current regulatory guidelines and scientific data to support the amendments proposed. These recommendations have been submitted to the ICH and are under consideration in the pre-Stage 1 consensus-building evaluation that will require comments of scientists and regulatory authorities. A new ICH guideline for the approval of biosimilars will bring global harmony and enhanced accessibility of safer biosimilars.

The interest in soft pneumatic actuators has been growing rapidly in robotics, owing to the contact adaptability with the material softness. However, these actuators are mostly controlled by rigid electronic pneumatic valves, which can hardly be integrated into the robot itself, limiting its mobility and adaptability. Recent advances in soft or electronics-free valve designs provide the potential to achieve an integrated soft robotic system with reduced weight and rigidity. Nevertheless, the challenge in valve response remains open. To enable dynamic control of a soft pneumatic actuator, a fast-response proportional valve is needed. In this paper, we explored the potential of Ecoflex-based magnetorheological elastomer (MRE) membrane to create a proportional valve that can be used in the control of a soft robot made from the same silicone material. Experimental characterization shows that the proposed MRE valve (30 mm \(\times\) 30 mm \(\times\) 15 mm, 30 grams) can hold pressure up to 41.3 kPa and regulate the airflow in an analog manner. The valve is used to perform closed-loop Proportional-Integral-Differential (PID) control with 50 Hz on a soft pneumatic actuator and is able to control the pressure within the actuator chamber with a root-mean-square error of 0.05 kPa.   Corresponding author(s) Email:   sihan.wang@eng.ox.ac.uk  

The Covid-19 lockdown reduced drastically human presence outdoors, providing an uncontrolled experiment for disentangling direct and indirect effects of human presence on animal fearfulness. We measured 18,494 flight initiation distances (FIDs, the distance at which individual animals fly away when approached by a human) from 1,333 populations of 202 bird species taken in four European cities both before, during and after the lockdown. Differential responses to lockdown among urban and rural habitats and between signing and non-singing birds showed that lockdown relaxed direct disturbance effects on birds in rural habitats, but increased indirect fear effects mediated by predator release (mainly feral cats) in cities.

An adult male Kemp’s ridley was found dead on the coast of Kenedy County, Texas in August 2019 with bilateral severe, diffuse granulomatous nephritis. Pan-bacterial 16S rRNA gene PCR and amplicon sequencing of affected tissue indicated the presence of a Neorickettsia. Neorickettsia is a genus of obligate intracellular Alphaproteobacteria that are transmitted by digenean trematodes. For further characterization, primers were designed to amplify and sequence the groEL gene. Phylogenetic analysis found that the organism was distinct from other known species to a degree consistent with a novel species. Immunohistochemistry using an antibody directed against a Neorickettsia surface protein showed bacterial clusters within the renal granulomas. A species-specific quantitative PCR was designed, and detected the organism within the liver and colon of the index case. A qPCR survey of grossly normal kidneys opportunistically collected from additional stranded sea turtle kidneys detected this organism in five of 15 Kemp’s ridley turtles, two of nine green turtles, and neither of two loggerhead turtles. Recognition of this novel organism in an endangered species is concerning; additional work is underway to further characterize the potential of this organism as a pathogen of sea turtles.

Human impacts such as habitat loss, climate change and biological invasions are radically altering biodiversity, with even greater effects projected into the future. Evidence suggests human impacts may differ substantially between terrestrial and freshwater ecosystems, but the reasons for these differences are poorly understood. We propose an integrative approach to explain these differences by linking impacts to the fundamental processes that structure communities: dispersal, speciation, ecological selection and ecological drift. Our goal is to provide process-based insights into why human impacts, and the responses to these impacts, may differ across ecosystem types within a mechanistic, eco-evolutionary comparative framework. To enable these insights, we review and synthesize i) how the four processes can influence diversity and dynamics in terrestrial and freshwater communities, focusing on whether their relative importance may or may not differ among ecosystems, and ii) how human impacts can alter terrestrial and freshwater biodiversity in different ways due to differences in process strength among ecosystems. Finally, we highlight research gaps and next steps, and discuss how this approach can provide new insights for conservation. By focusing on the processes that shape diversity in communities, we aim to mechanistically link human impacts to ongoing and future changes in ecosystems.

Newcastle disease virus (NDV) has severely affected the poultry industry in recent years. One of the best ways to protect yourself from this virus and lower your chance of a pandemic is by vaccination. The commercial vaccine does not adequately respond to pandemic strains. This study examines the potential function of formulated Haemagglutinin neuraminidase (HN) with Freund’s adjuvant against Newcastle disease virus. To this end, a recombinant Haemagglutinin neuraminidase (rHN) gene of the Newcastle disease virus was designed and expressed used by B.subtiles expression system. Four groups of mice were immunized by rHN in combination with Freund’s adjuvant, and commercial vaccine. The humoral immune test was then performed on the vaccinated mice, and the outcomes were compared to those of untreated animals (negative group). NDV was also administered through intranasal drop to the treated and control mouse groups. Body weight, survival, temperature variation, and the medical conditions of the samples were assessed. Mice that received the recombinant protein vaccination showed humoral reactions to the NDV. Also, co-administration of rHN with Freund’s adjuvant might increase the survival rate of the immunized mice by 92 percent. Two weeks after infection, the Freund’s adjuvant-treated group had a slight weight loss and a high body temperature. Additionally, compared to the group that received a commercial vaccination, this group had a greater HI antibody titer. Altogether, the results showed that the recombinant protein with the Freund’s adjuvant created better safety than the Commercial vaccine produced in Iran, thereby can be considered as a safe and reliable vaccine candidates against the Newcastle virus for further investigations.

A procedure for storage and retrieval of Digital information in DNA strings is discussed by constructing an error correction code which is capable of correcting indel errors and maintaining the stability of DNA strings. For correcting indel errors, Varshamov–Tenengolts algorithm is used. In the VT algorithm, syndrome is calculated using the position values of the retrieved word. Then, the wrongly added or deleted positions can be found by the syndrome and weight of the retrieved word. The stability of DNA strings depends on the proportionate occurrence of guanine (G) and cytosine (C). Reverse complementary property is essential for preventing de-hybridization. To ensure these properties, VT encoded information is mapped to DNA strings by appropriate choices of group homomorphisms. Code for any desired length(n) can be created using the construction methods presented in this paper. The code’s reverse complement distance is calculated by using the value of n.

By using the basic principle of the continuous damage mechanics as a reference, together with the statistical strength theory based on the Weibull distribution, a new constitutive model of fractured rock masses for deep underground engineering is proposed. In this model, a new definition of the fracture degree Ft has been proposed for the first time, which can quantitatively describe the fracturing process of a fractured rock mass. Based on the results of laboratory tests and numerical simulations for fractured rock mass specimens, the constitutive model with different fracture degrees are verified. Moreover, the applicability of two yield criteria (the M-C and D-P criteria) for describing the mesoscopic strength of rocks is analyzed. Finally, the effects of the random distribution parameters on the constitutive model are discussed in detail. The results show that the theoretical results agree well with the experimental and numerical results, and the constitutive model with the D-P criterion is better than the model with the M-C criterion.

Order and disorder govern protein functions, but there is a great diversity in disorder, from regions that are – and stay – fully disordered to conditional order. This diversity is still difficult to decipher even though it is encoded in the amino acid sequences. Here, we developed an analytic Python package, named pyHCA, to estimate the foldability of a protein segment from the only information of its amino acid sequence and based on a measure of its density in regular secondary structures associated with hydrophobic clusters, as defined by the Hydrophobic Cluster Analysis (HCA) approach. The tool was designed by optimizing the separation between foldable segments from databases of disorder (DisProt) and order (SCOPe (soluble domains) and OPM (transmembrane domains)). It allows to specify the ratio between order, embodied by regular secondary structures (either participating in the hydrophobic core of well-folded 3D structures or conditionally formed in intrinsically disordered regions) and disorder. We illustrated the relevance of pyHCA with several examples and applied it to the sequences of the proteomes of 21 species ranging from prokaryotes and archaea to unicellular and multicellular eukaryotes, for which structure models are provided in the AlphaFold2 databases. Cases of low-confidence scores related to disorder were distinguished from those of sequences that we identified as foldable but are still excluded from accurate modeling by AlphaFold2 due to a lack of sequence homologs or to compositional biases. Overall, our approach is complementary to AlphaFold2, providing guides to map structural innovations through evolutionary processes, at proteome and gene scales.

The classic chancre of primary syphilis is painless and frequently neglected. We present a 20-year-old male complaining of red, tender, enlarging, skin lesions on the forehead, left nose, and left forearm for almost 2 months with systemic symptoms of secondary syphilis, granulomatous type.

BACKGROUND: Although cardiac resynchronization therapy (CRT) is beneficial in most heart failure patients, up to 40% do not respond to CRT. It has been suggested that multipoint left ventricle pacing (MPP) would increase the response rate. AIM: To assess the CRT response rate at 6 months in patients implanted with a CRT device with the MPP feature activated early after the implant. METHODS This was a multicentre, prospective, open-label and non-randomized study. The primary endpoint was response to biventricular pacing defined as >15% relative reduction in left ventricular end-systolic volume (LVESV) comparing echocardiography measurements performed at baseline and 6 months by a core laboratory. Among secondary endpoints the combined endpoint of mortality or all-cause hospitalizations was evaluated. Primary study endpoint and clinical outcomes were compared to a Quarto II control cohort. RESULTS: 105 patients were included. The response rate was 64.6% (97.5% lower confidence bound 53%). Mean relative reduction in LVESV was 25.3% and mean absolute increase in LVEF was 9.4%. The subjects with device programmed using anatomical approach had showed a trend toward higher responder rate than those using the electrical approach (72% vs. 61.1%, p= 0.32). Compared with Quarto II, the combined endpoint of mortality and or all-cause hospitalizations was lower in Quarto III (12.4% vs 25.4%, p=0.004). CONCLUSIONS: Early activation of MPP was not associated to an advantage increasing echocardiography responders to CRT at 6 months of follow up. Nevertheless, MPP was associated with better clinical outcomes in comparison to a historical control cohort. Patients programmed using widest pacing cathodes had a numerically higher responder rate.

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