Picomolar level electrochemical detection of hydroquinone, catechol and resorcinol simultaneously using a MoS2 nano-flower decorated graphene.

Herein, a graphene-nano-molybdenum disulphide (pGr-MoS2), synthesized from pulverized graphite and using precursors of MoS2, was investigated for the electrochemical sensing of dihydroxy benzene isomers (DHBI): hydroquinone (HQ), catechol (CA), and resorcinol (RE). Interestingly, the material could sense the three isomers simultaneously, with well-defined peaks and an adequate potential difference between each peak. The detection limits (3σ method) of HQ, CA, and RE on the glassy carbon electrode (GCE) modified with pGr-MoS2 are 10-13, 10-12, and 10-8 M (i.e., 0.1 pM, 1 pM, and 10 nM), respectively, and are the lowest reported so far for the isomers. The pGr-MoS2/GCE exhibited selectivity towards DHBI, in the presence of other toxic contaminants and metal ions such as phenol, dinitrophenol, trinitrophenol, urea and glucose, Hg(II), Ca(II), Ni(II), Zn(II), Cu(II), Na(I) and K(I). A possible mechanism for this superior selectivity of pGr-MoS2 towards DHBI is discussed based on the structural properties of pGr-MoS2 with evidence. Further, the pGr-MoS2 sensor exhibited reproducibility (with six different electrodes), stability (≥90 days), and repeatability properties. The sensing performance was successfully demonstrated in real water samples such as ground-, tap-, and river- water spiked with HQ, CA, and RE.

Aegle marmelos differentially affects hepatic markers of glycolysis, insulin signalling pathway, hypoxia, and inflammation in HepG2 cells grown in fructose versus glucose-rich environment.

Fructose consumption is responsible for the onset of insulin resistance (IR), and metabolic syndrome. It possesses no functional utility in body and its detrimental effects on hepatic metabolic milieu are beyond those produced by glucose. The need of the hour is to identify fructose-induced IR as an unique pathological state to be managed differentially. The effect of aqueous leaf extract of Aegle marmelos (AM) on hepatic markers of insulin resistance using HepG2 cells cultured in either fructose or glucose-rich environment is investigated. Human hepatocellular carcinoma cells (HepG2) were grown under standard conditions in either-DMEM without glucose (NC), DMEM with high glucose 25 mM (Glu), DMEM-glucose+0.55 mM fructose (FC1), DMEM-glucose+1 mM fructose (FC2) or DMEM-glucose+1 mM fructose+0.1 µM insulin (FC3). The cells were treated with either AM, rutin, quercetin, metformin or pioglitazone and assessed for levels of hexokinase, phosphofructokinase (PFK), aldehyde dehydrogenase, phosphatidylinositol kinase (PI3K), signal transducer and activator of transcription-3 (STAT-3), mitochondrial target of rapamycin (mTOR), hypoxia-induced factor (HIF-1α), vascular endothelial growth factor (VEGF) and tumour necrosis factor (TNF-α). Summarily, when results from fructose- and glucose-rich environment were compared, then (1) IR was more pronounced in former; (2) AM performed better in former; (3) metformin and pioglitazone were equivocal in either; (4) rutin and quercetin showed deviant effects from AM; and lastly (5) effects of rutin were closer to AM than quercetin. We hypothesize that AM ameliorates fructose-induced IR through a mechanism which is distinct from standard drugs and not shared by individual phytoconstituents in toto.

Phase II study of MLN8237 (Alisertib) in advanced/metastatic sarcoma.

BACKGROUND: Aurora kinase A (AURKA) is commonly overexpressed in sarcoma. The inhibition of AURKA by shRNA or by a specific AURKA inhibitor blocks in vitro proliferation of multiple sarcoma subtypes. MLN8237 (alisertib) is a novel oral adenosine triphosphate-competitive AURKA inhibitor. PATIENTS AND METHODS: This Cancer Therapy Evaluation Program-sponsored phase II study of alisertib was conducted through the Alliance for Clinical Trials in Oncology (A091102). Patients were enrolled into histology-defined cohorts: (i) liposarcoma, (ii) leiomyosarcoma, (iii) undifferentiated sarcoma, (iv) malignant peripheral nerve sheath tumor, or (v) other. Treatment was alisertib 50 mg PO b.i.d. d1-d7 every 21 days. The primary end point was response rate; progression-free survival (PFS) was secondary. One response in the first 9 patients expanded enrollment in a cohort to 24 using a Simon two-stage design. RESULTS: Seventy-two patients were enrolled at 24 sites [12 LPS, 10 LMS, 11 US, 10 malignant peripheral nerve sheath tumor (MPNST), 29 Other]. The median age was 55 years; 54% were male; 58%/38%/4% were ECOG PS 0/1/2. One PR expanded enrollment to the second stage in the other sarcoma cohort. The histology-specific cohorts ceased at the first stage. There were two confirmed PRs in the other cohort (both angiosarcoma) and one unconfirmed PR in dedifferentiated chondrosarcoma. Twelve-week PFS was 73% (LPS), 44% (LMS), 36% (US), 60% (MPNST), and 38% (Other). Grade 3-4 adverse events: oral mucositis (12%), anemia (14%), platelet count decreased (14%), leukopenia (22%), and neutropenia (42%). CONCLUSIONS: Alisertib was well tolerated. Occasional responses, yet prolonged stable disease, were observed. Although failing to meet the primary RR end point, PFS was promising. TRIAL REGISTRATION ID: NCT01653028.

Characteristics of pain and their relationship to disease activity in UK patients with Behçet's syndrome: a prospective cohort study.

Background: Behçet's syndrome (BS) is a rare multi-systemic vasculitis of unknown aetiology. Fibromyalgia syndrome (FMS) is more prevalent in rheumatological conditions such-as BS, than the general population. However, there is limited research into the aetiology and characteristics of pain in BS. Objectives: To describe the pain characteristics and incidence of FMS in people with BS and investigate their relationship with BS disease activity. Methods: A cohort study of BS patients attending the Liverpool Behçet's Centre between February 2017 and March 2019. BS was defined using the International Study Group Criteria. BS severity was assessed using the Behçet's Disease Current Activity Form. FMS was determined from consultant diagnosis. Assessments of pain included: Pain Visual Analogue Scale (PVAS), Pain Mannequin, Brief Pain Inventory, EQ-5D-3L and Short Form McGill. Pain and FMS prevalence were compared between high and low disease activity. Results: 90% reported moderate-severe pain with a median PVAS score of 68/100 [38, 81]. 35.6% of participants had FMS and 46.5% experienced generalized pain. 76% of participants with high disease activity reported severe pain, compared to 39.1% with low disease activity (p = .003). Pain was more generalised in high disease activity (72%) compared to low disease activity (37.7%) (p = .003). FMS was more prevalent in the high disease activity group (52%) than the low disease activity group (29%) (p = .04). Conclusions: This is the first study to explore pain in participants with BS in the United Kingdom. The majority of BS patients experience moderate-severe widespread pain. Severe widespread pain is more prevalent in those with high disease activity. We have demonstrated a relationship between high disease activity, worse pain intensity, and FMS. This paper contributes to the understanding of two conditions which remain to be fully understood, FMS and BS, and generates new hypotheses to describe the interplay between.

Pharmacological Evaluation of the Anesthetic and Analgesic Potential of Injection Harsha 22: A Novel Polyherbal Local Anesthetic Formulation Intended for Parenteral Administration in Wistar Albino Rats.

Background: Local anaesthetics are medications that cause numbness that can be reversed by applying them topically. Local anaesthetics are clinically used to control pain during minor surgeries or to treat other acute and chronic pain. The present investigation intended to investigate the anesthetic as well as analgesic potential of Injection Harsha 22, a novel polyherbal formulation in Wistar albino rats. Methods: The anesthetic potential of Injection Harsha 22 was evaluated by a heat tail-flick latency (TFL) test, whereas the analgesic effect was elevated by electrical stimulation testing. Here, lignocaine (2%) was used as the standard anesthetic drug. Results: In TFL, Injection Harsha 22 showed anesthetic effects up to 90 minutes after application. Also, the duration of anesthesia in rats that were administered subcutaneously with Injection Harsha 22 was comparable to that of the rats treated with commercial lignocaine (2%). In an electrical stimulation test, single administration of Injection Harsha 22 to rats significantly prolonged analgesia compared with the normal control group. The median duration of analgesia in rats administered subcutaneously with Injection Harsha 22 and lignocaine solution was 40 minutes and 35 minutes, respectively. Furthermore, Injection Harsha 22 does not interfere with the hematopoietic system of the experiment animals. Conclusion: Thus, the present investigation established the in vivo anesthetic and analgesic potential of Injection Harsha 22 in experimental animals. Hence, it can be concluded that Injection Harsha 22 can become a prominent substitute for lignocaine as a local anaesthetic agent after establishing its efficacy through stringent clinical trials in humans.

A multivariate and quantitative assessment of medicinal plants used by the indigenous Malayali tribes in the Javadhu hills of Tiruvannamalai district, Tamil Nadu, India.

The study of medicinal plants with their traditional uses and related pharmacological studies has received more attention during the past several decades around the world. The Malayali tribes of the Javadhu Hills in the Eastern Ghats rely heavily on a system of traditional medicine for healthcare. A qualitative ethnographic method with a semi-structured questionnaire was used to interview 52 people across 11 localities in the Javadhu Hills. In the data analysis, descriptive statistics such as Use reports (UR), frequency of citations (FC), relative frequency of citations (RFC), informant agreement ratio (IAR), fidelity level (FL), and informant consensus factor (FIC) were studied. In the current investigation, 146 species from 52 families and 108 genera were discovered to treat 79 diseases. Leguminosae and Apocynaceae were the dominant families (12 species each). The most frequently used life form was the herb and the plant part were the leaf. The majority were being harvested from natural resources. Most medicines were taken orally. The most frequently cited species are Moringa oleifera and Syzygium cumini. The illnesses were divided into 21 categories. The majority of the plants mentioned are utilised to increase human immunity and health. The principal ailment (general health) was revealed by two-way cluster analysis and PCA. The species Litsea decanensis, Phoebe paniculata, Commiphora caudata, etc., were new records for the Javadhu hills according to a comparison between the current study and previous local and regional research. Documenting novel ethnomedicinal species and their therapeutic applications will encourage more phytochemical and pharmacological research and may even result in the creation of new medications. Furthermore, the study's significant novelty is that principle component analysis and two-way cluster analysis clearly revealed that the species that are used to treat various diseases, as well as species that are closely associated with treating specific ailment categories, are distinct. Significantly, species recorded in this study rely on maintaining and improving general body health of humans.

Hydroponic system for the treatment of anaerobic liquid.

The effluent from anaerobic digestion process has high concentrations of nutrients, particularly nitrogen, essential for plant growth but is not suitable for direct disposal or application due to high chemical oxygen demand (COD), low dissolved oxygen (DO), odour issues and is potentially phytotoxic. This research explored the optimum conditions of anaerobic effluent for application and dilutions of the effluent required to obtain better plant growth. A small-scale hydroponic system was constructed in a glasshouse to test different concentrations of anaerobic effluent against a commercial hydroponic medium as the control for the growth of silverbeet. It was found that the survival of silverbeet was negatively affected at 50% concentration due to low DO and NH(4) toxicity. The concentration of 20% anaerobic liquid was found to be the most efficient with highest foliage yield and plant growth. The hydroponic system with 20% concentrated effluent had better utilisation of nutrients for plant growth and a COD reduction of 95% was achieved during the 50-day growth period. This preliminary evaluation revealed that the growth and development of silverbeet was significantly lower in anaerobic effluent compared with a commercial hydroponic plant growth solution. The nutrient quality of anaerobic effluent could be highly variable with the process and the waste material used and dilution may depend on the nutrient content of the effluent. It is recommended that, a pre-treatment of the effluent to increase DO and reduce ammonium content is required before plant application, and simple dilution by itself is not suitable for optimum plant growth in a hydroponic system.

Administration of Caesalpinia bonduc Seed Extracts Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia (BPH) in Male Wistar Rats.

Introduction: Benign prostatic hyperplasia (BPH) is a major chronic disease affecting men, and the therapeutic agents currently used to manage it have significant side effects. As a result, an alternative medicine with improved therapeutic properties with no side effects is desperately needed. The current investigation aims to study whether the Caesalpinia bonduc seed extracts (ethanolic-A, hydroalcoholic-B, and aqueous-C) have inhibitory potential on testosterone propionate (TP)-induced BPH in Wistar rats. Methods: Wistar rats (male) were randomly allocated to one of five groups: control, BPH (TP-3 mg/kg, subcutaneously daily), low dose (TP + C. bonduc seed extracts - 200 mg/kg body weight), high dose (TP + C. bonduc seed extracts - 400 mg/kg body weight), and standard drug (TP + finasteride - 10 mg/kg body weight). At the end of drug treatment, the rats were sacrificed and their serum and prostates were taken for biochemical and histological studies. Results: C. bonduc seed extracts treatment significantly decreased prostate weight and prostatic index in rats with TP-induced BPH. The seed extracts exhibited a potent inhibitory effect on dihydrotestosterone (DHT) in serum and prostate. In addition, the PSA level in the serum showed a noteworthy decrease in comparison with the BPH group. Histopathological examination also indicated that extracts improved the tissue morphology of the prostate significantly. Out of three extracts tested, ethanolic and hydroalcoholic extract recorded significant effect. Finally, liquid chromatography quadrupole time-of-flight mass spectrometry (LC/MS-QTOF) analysis showed that the major compounds present in the extracts were tocopherols, fucosterol, linoleic acid, ß-amyrin, ß-sitosterol, campesterol, cassane furanoditerpene, norcassane furanoditerpene and other diterpenes. Conclusion: Thus, C. bonduc seed extracts could be a potential source for the formulation of new drug for managing BPH. To the best of our knowledge, this is the first scientific animal investigation into the use of C. bonduc seed extract for the management of BPH.

An efficacy and safety report based on randomized controlled single-blinded multi-centre clinical trial of ZingiVir-H, a novel herbo-mineral formulation designed as an add-on therapy in adult patients with mild to moderate COVID-19.

OBJECTIVE: Coronaviruses, hence named because of the crown-like spikes on the viral envelope, are members of Coronaviridae family and Order Nidovirales. SARS-CoV-2 is the seventh human pathogenic coronavirus identified after HCoV-229E, HCoV-OC43, SARS-CoV (SARS-CoV-1), HCoV-NL63, CoV-HKU1, and MERS-CoV. SARS-Cov-2 is highly similar to SARS-CoV. COVID-19 is the corresponding acute disease caused by SARS-CoV-2 that was initially reported in Wuhan, China towards the end of 2019 and spread to millions of humans globally. Unfortunately, limited studies were available on the efficacy of antiviral drugs to treat COVID-19 at the time of this study. ZingiVir-H is an Ayurvedic formulation for use in early therapy of viral disease. This clinical trial was planned to investigate (1) the efficacy and safety of ZingiVir-H and (2) the efficacy of ZingiVir-H as an add-on therapy to the standard of care in hospitalized adults diagnosed with COVID-19. METHODS: A total of 123 eligible subjects as per inclusion criteria were randomized within the study. Three subjects later declined to participate in the study and four subjects didn't meet inclusion criteria, which brought the final evaluable subject count to 116 for the efficacy and safety endpoint analysis. Thus, a total of 116 patients were equally randomised into two groups, namely, ZingiVir-H and Placebo for this clinical trial. The study patients were assigned to receive either ZingiVir-H or Placebo along with the standard of care as per the National Indian COVID-19 treatment protocol. The time interval until a negative RT-PCR obtained, was evaluated during treatment with ZingiVir-H or Placebo for ten days. Liver and kidney function tests were regularly assessed to ensure the safety profile of ZingiVir-H. RESULTS: The study found that patients who were administered ZingiVir-H had a median recovery time of 5 days (95% confidence interval (CI) 5-5) when compared to 6 days (95% CI 5-6) in those who received Placebo. Besides, in Ordinal Scale analysis of all the patients treated with ZingiVir-H demonstrated significant redistribution to a better clinical status from ordinal scale 5 to 6 and 7 within five to seven days when compared to that of placebo treatment. The time required for clinical improvement and the number of days needed for hospitalization was significantly less in the ZingiVir-H treated group when compared to placebo. The absence of liver and kidney function changes affirmed the safety profile of ZingiVir-H. No serious adverse events were reported in ZingiVir-H treated patients. CONCLUSION: We found that ZingiVir-H is effective and safe in managing COVID-19 infections and delaying the disease progression from mild to moderate and moderate to severe. To the best of our knowledge, this is the first clinical trial report on the efficacy/safety of a herbo-mineral Ayurvedic drug against COVID-19 as of yet. TRIAL REGISTRATION: Clinical Trial Registry of India CTRI/2020/04/024883. Registered on 28/04/2020.

Methemoglobin and the response to inhaled nitric oxide in persistent pulmonary hypertension of the newborn.

BACKGROUND: We aimed to investigate whether the change in methemoglobin levels (ΔMHb) predicts oxygenation response to inhaled nitric oxide (iNO) in persistent pulmonary hypertension of the newborn (PPHN) with lung disease, with or without pulmonary hypoplasia. METHODS: In this prospective observational study, infants were categorized based on ΔMHb and oxygenation response (ΔPaO2/FiO2) following iNO: ΔMHb ≤0 or ΔMHb>0, and ΔPaO2/FiO2 < 20 mmHg (Non-responder) or≥20 mmHg (Responder). ΔMHb levels were compared among infants with or without pulmonary hypoplasia. RESULTS: Among infants with pulmonary hypoplasia (n = 28), ΔMHb was not associated with an oxygenation response to iNO or survival without ECMO. Among infants without hypoplasia (n = 29), subjects with ΔMHb>0 following iNO (n = 21) had a greater ΔPaO2/FiO2 (median, 64 mmHg; IQR, 127; p < 0.01) and 100% survival without extracorporeal membrane oxygenation (ECMO) when compared to infants with ΔMHb ≤0 (n = 8; median 10 mmHg; IQR, 33). CONCLUSIONS: PPHN secondary to lung disease without hypoplasia with increased ΔMHb following iNO was associated with better oxygenation response and survival without ECMO compared to subjects without an increase in MHb.

Advancements in AAV-mediated Gene Therapy for Pompe Disease.

Pompe disease (glycogen storage disease type II) is caused by mutations in acid α-glucosidase (GAA) resulting in lysosomal pathology and impairment of the muscular and cardio-pulmonary systems. Enzyme replacement therapy (ERT), the only approved therapy for Pompe disease, improves muscle function by reducing glycogen accumulation but this approach entails several limitations including a short drug half-life and an antibody response that results in reduced efficacy. To address these limitations, new treatments such as gene therapy are under development to increase the intrinsic ability of the affected cells to produce GAA. Key components to gene therapy strategies include the choice of vector, promoter, and the route of administration. The efficacy of gene therapy depends on the ability of the vector to drive gene expression in the target tissue and also on the recipient's immune tolerance to the transgene protein. In this review, we discuss the preclinical and clinical studies that are paving the way for the development of a gene therapy strategy for patients with early and late onset Pompe disease as well as some of the challenges for advancing gene therapy.

Typical signature of DNA damage in white blood cells: a pilot study on etheno adducts in Danish mother-newborn child pairs.

The impact of DNA damage commonly thought to be involved in chronic degenerative disease causation is particularly detrimental during fetal development. Within a multicenter study, we analyzed 77 white blood cell (WBC) samples from mother-newborn child pairs to see if imprinting of DNA damage in mother and newborn shows a similar pattern. Two adducts 1,N(6)-ethenodeoxyadenosine (epsilondA) and 3,N(4)-ethenodeoxycytidine (epsilondC) were measured by our ultrasensitive immunoaffinity (32)P-post-labeling method. These miscoding etheno-DNA adducts are generated by the reaction of lipid peroxidation (LPO) end products such as 4-hydroxy-2-nonenal with DNA bases. Mean epsilondA and epsilondC levels when expressed per 10(9) parent nucleotides in WBC-DNA from cord blood were 138 and 354, respectively; in maternal WBC-DNA, the respective values were 317 and 916. Thus, the DNA-etheno adduct levels were reliably detectable and about two times lower in child cord blood, the difference being significant at P < 0.0004. Analysis of epsilondA and epsilondC levels in cord versus maternal blood WBC showed strong positive correlations (R(2) approximately 0.9, P < 0.00001). In conclusion, LPO-induced DNA damage arising from endogenous reactive aldehydes in WBC of both mother and newborn can be reliably assessed by epsilondA and epsilondC as biomarkers. The high correlation of etheno adduct levels in mother and child WBC suggests that a typical signature of DNA damage is induced similarly in fetus and mother. Prospective cohort studies have to reveal whether these two WBC-DNA adducts could serve as risk indicator for developing hematopoietic cancers and other disorders later in life.

Sec2 protein contains a coiled-coil domain essential for vesicular transport and a dispensable carboxy terminal domain.

SEC2 function is required at the post-Golgi apparatus stage of the yeast secretory pathway. The SEC2 sequence encodes a protein product of 759 amino acids containing an amino terminal region that is predicted to be in an alpha-helical, coiled-coil conformation. Two temperature-sensitive alleles, sec2-41 and sec2-59, encode proteins truncated by opal stop codons and are suppressible by an opal tRNA suppressor. Deletion analysis indicates that removal of the carboxyl terminal 251 amino acids has no apparent phenotype, while truncation of 368 amino acids causes temperature sensitivity. The amino terminal half of the protein, containing the putative coiled-coil domain, is essential at all temperatures. Sec2 protein is found predominantly in the soluble fraction and displays a native molecular mass of greater than 500 kD. All phenotypes of the temperature-sensitive sec2 alleles are partially suppressed by duplication of the SEC4 gene, but the lethality of a sec2 disruption is not suppressed. The sec2-41 mutation exhibits synthetic lethality with the same subset of the late acting sec mutants as does sec4-8 and sec15-1. The Sec2 protein may function in conjunction with the Sec4 and Sec15 proteins to control vesicular traffic.

Multicenter study to assess potential hazards from exposure to lipid peroxidation products in soya bean oil from Trilucent breast implants.

In response to a Hazard Notice by the Medical Devices Agency of the UK in 2000 regarding the Trilucent breast implant (TBI), an expert panel was convened to implement a research program to determine whether genotoxic compounds were formed in the soybean oil filler (SOF) of TBIs and whether these could be released to produce local or systemic genotoxicity. The panel established a research program involving six laboratories. The program recruited 47 patients who had received TBIs (9 patients had received silicone implants previously). A reference group (REBI) of 34 patients who had exchanged either silicone (17 patients) implants (REBI-E) or patients (17) who were to receive primary implantation augmentation with silicone (REBI-PIA), and who were included as needed to increase either the pre- or post-explantation sample number. Of the 17 REBI-E patients, 5 had silicone implants and 12 had saline implants previously (prior to the last exchange). Investigation was undertaken before and after replacement surgery in the TBI patients and before and after replacement or augmentation surgery in the REBI patients. The pre- to post-operative sample interval was 8-12 weeks. Pre-operative samples were collected within 7 days prior to the operation. Information on a variety of demographic and behavioral features was collected. Biochemical and biological endpoints relating to genotoxic lipid peroxidation (LPO) products potentially formed in the SOF, and released locally or distributed systemically, were measured. The SOF of explanted TBIs was found to have substantial levels of LPO products, particularly malondialdehyde (MDA), and low levels of trans-4-hydroxy-2-nonenal (HNE) not found in unused implants. Mutagenicity of the SOF was related to the levels of MDA. Capsules that formed around TBIs were microscopically similar to those of reference implants, but MDA-DNA adducts were observed in capsular macrophages and fibroblasts of only TBI capsules. These cell types are not progenitors of breast carcinoma (BCa) and the location of the implants precludes LPO products reaching the mammary epithelial cells which are progenitors of BCa. Blood levels of LPO products were not increased in TBI patients compared to REBI patients and did not change with explantation. In TBI patients, white blood cells did not show evidence of increased levels of LPO-related aldehyde DNA adducts. In conclusion, based on a number of measured parameters, there was no evident effect that would contribute to breast or systemic cancer risk in the TBI patients, and the recommended treatment of TBI patients involving explantation was judged appropriate.

A Randomized Study Comparing the Incidence of Postoperative Pain After Phrenic Nerve Infiltration Vs Nonphrenic Nerve Infiltration During Thoracotomy.

Thoracotomy is a common surgical procedure performed worldwide for lung disease. Despite major advances in analgesia, patients still experience severe shoulder, central back and surgical incision site pain in the postoperative period. This study aimed to assess whether intraoperative phrenic nerve infiltration reduces the incidence of postoperative pain and improves peak flow volume measurements during incentive spirometry. 90 patients undergoing open lobectomy were randomly assigned to have phrenic nerve infiltration (n = 46) or not (n = 44). The phrenic nerve infiltration group received 10 mL of 0.25% bupivacaine into the periphrenic fat pad. Preoperative assessments of spirometry and pain scores were recorded (at rest and with movement). Postoperative assessments included peak flow and pain measurements at intervals up to 72 hours. Less shoulder pain was experienced with phrenic nerve infiltration up to 6 hours postsurgery at rest (P = 0.005) and up to 12 hours with movement (P < 0.001). Reduced back pain was reported in the phrenic nerve infiltration group up to 6 hours after surgery both at rest (P = 0.001) and with movement (P = 0.00). Phrenic nerve infiltration reduced pain at the incision site for up to 3 hours both at rest (P < 0.001) and with movement (P = 0.001). Spirometry readings dropped in both groups with consistently lower readings at baseline and follow-up in the PNI group (P = 0.007). Lower analgesic usage of patient controlled analgesia morphine (P < 0.0001), epipleural bupivacaine (P = 0.001), and oramorph/zomorph (P = 0.0002) were recorded. Our findings indicate that the use of phrenic nerve infiltration significantly reduced patient pain scores during the early postoperative period, particularly during movement. We believe that each technique has advantages and disadvantages; however, further studies with large sample size are warranted.

Radiomics-Based Intracranial Thrombus Features on CT and CTA Predict Recanalization with Intravenous Alteplase in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Thrombus characteristics identified on non-contrast CT (NCCT) are potentially associated with recanalization with intravenous (IV) alteplase in patients with acute ischemic stroke (AIS). Our aim was to determine the best radiomics-based features of thrombus on NCCT and CT angiography associated with recanalization with IV alteplase in AIS patients and proximal intracranial thrombi. MATERIALS AND METHODS: With a nested case-control design, 67 patients with ICA/M1 MCA segment thrombus treated with IV alteplase were included in this analysis. Three hundred twenty-six radiomics features were extracted from each thrombus on both NCCT and CTA images. Linear discriminative analysis was applied to select features most strongly associated with early recanalization with IV alteplase. These features were then used to train a linear support vector machine classifier. Ten times 5-fold cross-validation was used to evaluate the accuracy of the trained classifier and the stability of the selected features. RESULTS: Receiver operating characteristic curves showed that thrombus radiomics features are predictive of early recanalization with IV alteplase. The combination of radiomics features from NCCT, CTA, and radiomics changes is best associated with early recanalization with IV alteplase (area under the curve = 0.85) and was significantly better than any single feature such as thrombus length (P < .001), volume (P < .001), and permeability as measured by mean attenuation increase (P < .001), maximum attenuation in CTA (P < .001), maximum attenuation increase (P < .001), and assessment of residual flow grade (P < .001). CONCLUSIONS: Thrombus radiomics features derived from NCCT and CTA are more predictive of recanalization with IV alteplase in patients with acute ischemic stroke with proximal occlusion than previously known thrombus imaging features such as length, volume, and permeability.

The toxicity of ammonia/ammonium to the vermifiltration wastewater treatment process.

This study was undertaken to assess the toxicity of ammonia/ammonium to key species within the vermifiltration process. The key species, the earthworm Eisenia fetida, was subjected to a series of tests in solid phase mesocosms and full-scale units. The solid phase tests showed a relatively low toxicity to ammonium with ammonium chloride having an LC50 for ammonium of 1.49 g/kg. Ammonium sulfate did not show an effect on mortality at 2 g/kg ammonium. The full-scale units showed that ammonia hydroxide can change the pH and concentration of ammonia in wastewater and while it caused some mortality to the worms its overall affect on system functioning was minimal with no significant difference in terms of worm survival found between treatments. The affect on nitrifying bacteria was also minimal with no linear trend shown with ammonia concentration.

Toxicity of domestic wastewater pH to key species within an innovative decentralised vermifiltration system.

The development of innovative decentralised wastewater treatment systems is pertinent to environmental sustainability. However for their appropriate use they require significant research and design to ensure they can be relied upon in the future and in most cases they have received less attention and research than large-scale sewage systems. This study assessed the likelihood of biological inhibition and disruption from pH to key species for vermifiltration. The test firstly assessed the buffer capacity of a vermicompost + manure media finding it had a relatively high buffering capacity for pH. The toxicity after the buffer capacity experiment showed that the species would survive between pH levels of 6.2 and 9.7. At the higher and lower pH levels however the survival of juveniles was impaired, probably due to their ability to uptake greater amounts of soluble salts and inability to regulate them. Overall the study showed that the tolerance of the key vermifiltration species to pH was far less than their survival as previously proposed and further research assessing their long-term population dynamics in a vermifiltration system with pH is warranted.

Novel inhibition of PIM2 kinase has significant anti-tumor efficacy in multiple myeloma.

The PIM kinase family (PIM1, 2 and 3) have a central role in integrating growth and survival signals, and are expressed in a wide range of solid and hematological malignancies. We now confirm that PIM2 is overexpressed in multiple myeloma (MM) patients, and within MM group it is overexpressed in the high-risk MF subset (activation of proto-oncogenes MAF/MAFB). This is consistent with our finding of PIM2's role in key signaling pathways (IL-6, CD28 activation) that confer chemotherapy resistance in MM cells. These studies have identified a novel PIM2-selective non-ATP competitive inhibitor (JP11646) that has a 4 to 760-fold greater suppression of MM proliferation and viability than ATP-competitive PIM inhibitors. This increased efficacy is due not only to the inhibition of PIM2 kinase activity, but also to a novel mechanism involving specific downregulation of PIM2 mRNA and protein expression not seen with the ATP competitive inhibitors. Treatment with JP11646 in xenogeneic myeloma murine models demonstrated significant reduction in tumor burden and increased median survival. Altogether our findings suggest the existence of previously unrecognized feedback loop(s) where PIM2 kinase activity regulates PIM2 gene expression in malignant cells, and that JP11646 represents a novel class of PIM2 inhibitors that interdicts this feedback.