Article Gate
Not a member yet
471 research outputs found
Sort by
Platelet-Rich Plasma and Adipose-Derived Mesenchymal Stem Cells in Association with Arthroscopic Microfracture of Knee Articular Cartilage Defects: A Pilot Randomized Controlled Trial
Full text linkBackground. This study aims to compare the effects of platelet-rich plasma (PRP) alone or in combination with adipose-derived mesenchymal stem cells (AD-MSCs) in patients affected by cartilage defects, undergoing knee arthroscopic microfracture. Methods. Thirty-eight patients diagnosed with a knee monocompartmental cartilage defect (Outerbridge grade IV) on the MRI, underwent an arthroscopic procedure. After the confirmation of the lesion, they all received the same bone marrow stimulation technique (microfracture) and were randomized into two groups: the first one had additional PRP injection (group A), while the second received PRP and AD-MSC injection (group B). Knee assessment and pain score were documented with Knee Injury Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) score, Short-Form (SF) 12, and Visual Analogue Scale (VAS) before the treatment and at 1, 3, 6, and 12 months of follow-up postoperatively. An additional arthroscopic procedure, performed in four patients for a subsequent meniscal lesion, let us evaluate cartilage evolution by performing a macro/microscopical assessment on cartilage biopsy specimens. Results. At the 12-month follow-up, both groups showed a comparable functional improvement. The scores on the IKDC form, KOOS, pain VAS, and SF-12 significantly improved from baseline () to 12 months postoperatively in both treatment groups. The four second-look arthroscopies showed a complete repair of the articular defects by smooth solid cartilage layer, with a good chondrocytic population, in both groups. A thick smooth hyaline-like cartilage with a predominantly viable cell population and normal mineralization (a form closely resembling native tissue) was observed in group B. Conclusions Modern regenerative medicine techniques, such as PRP and AD-MSC, associated with traditional arthroscopic bone marrow stimulating techniques, seem to enhance cartilage restoration ability. The preliminary results of this pilot study encourage the synergic use of these regenerative modulating systems to improve the quality of the regenerated cartilage
Cross-Resistance Pattern and Genetic Studies in Spirotetramat-Resistant Citrus Red Mite, Panonychus citri (Acari: Tetranychidae)
Full text linkIn the laboratory, an acaricide-susceptible strain of the citrus red mite, Panonychus citri (McGregor) (LS-FJ), was used to screen for resistance to spirotetramat. A spirotetramat-resistant strain (ST-NK) obtained after continuous selections through 15 selection cycles (45 generations) exhibited 1668.4-fold greater resistance when compared to the parent generation. Instability of the spirotetramat resistance in the mites was observed during 11 months under spirotetramat-free laboratory conditions. Cross-resistance to spirodiclofen and spiromesifen was detected both in eggs and larvae, but not to five other tested acaricides. Probit lines for F1 heterozygous progeny indicated that the resistance to spirotetramat in the mites was autosomal with neither sex linkage nor maternal effects. The degrees of dominance were 0.15 and 0.23 for the diploid F1 of LS-FJ♀ × ST-NK♂ and ST-NK♀ × LS-FJ♂, and 0.07 and 0.13 for haploid F2 of LS-FJ♀ × ST-NK♂ and ST-NK♀ × LS-FJ♂, respectively, which indicated that the resistance was incompletely dominant. The χ2 analyses from the response of a backcross of crossed F1 progeny and ST-NK and F2 progeny showed that multiple genes are responsible for resistance to spirotetram
Exploring Real World Outcomes with Nivolumab Plus Ipilimumab in Patients with Metastatic Extra-Pulmonary Neuroendocrine Carcinoma (EP-NEC)
Full text linkBackground: Dual utilization of the immune checkpoint inhibitors (ICPIs) nivolumab plus ipilimumab has demonstrated clinical promise in the treatment of patients with refractory high-grade neuroendocrine neo-plasms (NENs) in phase II clinical trials (DART SWOG 1609 and CA209), while single agent ICPIs have largely been ineffective for these types of tumors. While both trials demonstrated promising results in high grade NENs, there was no adequate description of the association between tumor differentiation (high-grade well-differentiated neuroendocrine tumor vs poorly-differentiated extra-pulmonary neuroendocrine carcinoma (EP-NEC) and ICPI outcomes in the DART SWOG 1609 trial. Our study reports on the effectiveness and toxicity profile of dual ICPIs in a real world second-line EP-NEC patient population. Methods: Data on metastatic EP-NEC patients, treated with either ICPIs (single and dual ICPIs) or chemo-therapy in the second-line setting, were retrieved from databases of three comprehensive cancer centers. Associations between treatment characteristics and outcomes, including progression-free survival (PFS) and overall survival (OS), were evaluated. Results: From 2007 to 2020, we identified 70 patients with metastatic EP-NEC (predominantly of gastro-enteropancreatic origin), of whom 42 patients (23 males, 19 females, median age 62 years old) were eligible for the final analysis. All patients were refractory to platinum etoposide doublet chemotherapy in the first-line setting. The median PFS for patients who received dual ICPIs (11 patients), single agent ICPI (8 patients), and cytotoxic chemotherapy (23 patients) was 258 days, 56.5 days, and 47 days, respectively (p = 0.0001). Median overall survival (OS) for those groups was not reached (NR), 18.7 months, and 10.5 months, respectively (p = 0.004). There were no significant differences in treatment outcomes in patients according to tumor mismatch repair (MMR) or tumor mutational burden (TMB) status. Grade 3–4 adverse events (AEs) were reported in 11.1% of the patients who received dual ICPIs; however, none of these AEs led to permanent treatment discontinuation. Conclusions: In the second-line setting, patients with EP-NECs treated with dual ICPIs (nivolumab plus ipilimumab) experienced improved PFS and OS compared to patients treated with single agent ICPI or cytotoxic chemotherapy. These results echo some of the current evidence for ICPIs in grade 3 NENs and need to be validated in future prospective studies
Correlation of Renal Scarring to Urinary Tract Infections and Vesicoureteral Reflux in Children
Full text linkObjective. To study the association of the grade of vesicoureteral reflux (VUR) and urinary tract infections (UTI) with renal scarring at the first clinical presentation of patients who underwent antireflux surgery. Materials and methods. Between 2015 and 2020, 150 patients (194 units) who underwent antireflux surgery had dimercaptosuccinic acid (DMSA) renal scans preoperatively. Patients were classified into the nonscar and scar groups according to DMSA scan results. Moreover, cases were classified into afebrile UTI, febrile UTI, and antenatal hydronephrosis (ANH) according to the mode of presentation. We correlated the mode of presentation and the grade of VUR to the presence/absence of renal scars in both groups. Results. The mean follow-up was 45 months preoperatively. The mode of presentation was afebrile, febrile UTIs, and antenatal hydronephrosis in (50, 14), (20, 46), and (10, 10) patients in the nonscar and scar groups, respectively. Of the 20 patients who presented ANH, 10 (50%) had scars. Clinical presentation was correlated to the presence of renal scarring and its degree. The scar group had significantly higher grades of VUR than the nonscar group (grades I–II (50 units versus 10 units), grade III (28 units versus 40 units), and grade IV–V (22 units versus 44 units) for the nonscar versus scar groups, respectively (value <0.001). Conclusion. Renal scarring is associated with higher grades of reflux and urinary tract infections. We advocate further research investigating infants who had UTIs with or without fever for early detection of reflux
Coagulation Parameters in Human Immunodeficiency Virus Infected Patients: A Systematic Review and Meta-Analysis
Full text linkBackground. Coagulation abnormalities are common complications of human immunodeficiency virus (HIV) infection. Highly active antiretroviral treatment (HAART) decreased the mortality of HIV but increased coagulopathies. HIV-related thrombocytopenia, prolonged prothrombin time (PT), activated partial thromboplastin time (APTT), and high D-dimer level commonly manifested in patients with HIV. Thus, this study is aimed to compare coagulation parameters of HAART-treated and HAART-naïve HIV-infected patients with HIV-seronegative controls. Methods. A systematic literature search was conducted using the databases PubMed/MEDLINE, Embase, Web of Science, and Google Scholar of studies published until July 2021. The primary outcome of interest was determining the pooled mean difference of coagulation parameters between HIV-infected patients and seronegative controls. The Joana Briggs Institute (JBI) critical appraisal tool was used for quality appraisal. Statistical analyses were performed using Stata11.0 software. The statistical results were expressed as the effect measured by standardized mean difference (SMD) with their related 95% confidence interval (CI). Results. A total of 7,498 participants (1,144 HAART-naïve patients and 2,270 HAART-treated HIV-infected patients and 3,584 HIV-seronegative controls) from 18 studies were included. HIV-infected patients (both on HAART and HAART-naive) exhibited significantly higher levels of PT than HIV-seronegative controls (SMD = 0.66; 95% CI: 0.53–0.80 and SMD = 1.13; 95% CI: 0.60–2.0, respectively). The value of APTT was significantly higher in patients with HIV on HAART than in seronegative controls. However, the values of PLT count, APTT, and fibrinogen level were significantly higher in seronegative controls. Besides, the level of fibrinogen was significantly higher in HAART-treated than treatment-naïve patients (SMD = 0.32; 95%CI: 0.08, 0.57). Moreover, the level of APTT and PT had no statistical difference between HAART and HAART-naïve HIV-infected patients. Conclusions. This study identified that HIV-infected patients are more likely to develop coagulation abnormalities than HIV-seronegative controls. Therefore, coagulation parameters should be assessed regularly to prevent and monitor coagulation disorders in HIV-infected patients
Ethnopharmacology, Biological Evaluation, and Chemical Composition of Ziziphus spina-christi (L.) Desf.: A Review
Full text linkMedicinal plants are the primary raw materials used in the production of medicinal products all over the world. As a result, more study on plants with therapeutic potential is required. The tropical tree Ziziphus spina belongs to the Rhamnaceae family. Biological reports and traditional applications including management of diabetes and treatment of malaria, digestive issues, typhoid, liver complaints, weakness, skin infections, urinary disorders, obesity, diarrhoea, and sleeplessness have all been treated with different parts of Z. spina all over the globe. The plant is identified as a rich source of diverse chemical compounds. This study is a comprehensive yet detailed review of Z. spina based on major findings from around the world regarding ethnopharmacology, biological evaluation, and chemical composition. Scopus, Web of Science, BioMed Central, ScienceDirect, PubMed, Springer Link, and Google Scholar were searched to find published articles. From the 186 research articles reviewed, we revealed the leaf extract to be significant against free radicals, microbes, parasites, inflammation-related cases, obesity, and cancer. Chemically, polyphenols/flavonoids were the most reported compounds with a composition of 66 compounds out of the total 193 compounds reported from different parts of the plant. However, the safety and efficacy of Z. spina have not been wholly assessed in humans, and further well-designed clinical trials are needed to corroborate preclinical findings. The mechanism of action of the leaf extract should be examined. The standard dose and safety of the leaf should be established.
1. Introduction
People have resorted to natural sources for cures for various ailments since ancient times [1, 2]. For millennia, people throughout the world have relied on medicinal herbs or plants [3]. Even more impressively, almost 25% of modern drugs are derived from the stem of plants in some way. This shows a robust foundation for plant-derived medicines [4]. Many current medications, nutraceuticals, nutritional supplements, and pharmaceutical products are based on these compounds. Since the development of bacterial and fungal resistance and many other diseases has become an increasing concern, there has been an upsurge in interest in the therapeutic capabilities of traditional medicines. No extensive reviews of Z. spina have been found, according to our literature search. There is only one attempt to review the plants in 2012 [5]. Ethnopharmacology, origin and distribution, taxonomic, morphological, biological evaluation, and chemical composition are examined in this study, which provides a complete overview and up-to-date information on the therapeutic properties of Z. spina with emphasis on its biological activity and chemical composition
Overlap of high-risk individuals predicted by family history, and genetic and non-genetic breast cancer risk prediction models: implications for risk stratification
Full text linkFamily history, and genetic and non-genetic risk factors can stratify women according to their individual risk of developing breast cancer. The extent of overlap between these risk predictors is not clear.
Methods
In this case-only analysis involving 7600 Asian breast cancer patients diagnosed between age 30 and 75 years, we examined identification of high-risk patients based on positive family history, the Gail model 5-year absolute risk [5yAR] above 1.3%, breast cancer predisposition genes (protein-truncating variants [PTV] in ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, or TP53), and polygenic risk score (PRS) 5yAR above 1.3%.
Results
Correlation between 5yAR (at age of diagnosis) predicted by PRS and the Gail model was low (r=0.27). Fifty-three percent of breast cancer patients (n=4041) were considered high risk by one or more classification criteria. Positive family history, PTV carriership, PRS, or the Gail model identified 1247 (16%), 385 (5%), 2774 (36%), and 1592 (21%) patients who were considered at high risk, respectively. In a subset of 3227 women aged below 50 years, the four models studied identified 470 (15%), 213 (7%), 769 (24%), and 325 (10%) unique patients who were considered at high risk, respectively. For younger women, PRS and PTVs together identified 745 (59% of 1276) high-risk individuals who were not identified by the Gail model or family history.
Conclusions
Family history and genetic and non-genetic risk stratification tools have the potential to complement one another to identify women at high risk
Immune microenvironment, homologous recombination deficiency, and therapeutic response to neoadjuvant chemotherapy in triple-negative breast cancer: Japan Breast Cancer Research Group (JBCRG)22 TR
Full text linkTriple-negative breast cancer (TNBC) is a biologically diverse disease, with characteristics such as homologous recombination deficiency (HRD), gene mutation, and immune reactions. Japan Breast Cancer Research Group 22 is a multicenter trial examining TNBC’s response to neoadjuvant chemotherapy (NAC) according to the HRD status. This translational research investigated the clinical significance of the immune microenvironment of TNBC in association with HRD, tumor BRCA1/2 (tBRCA1/2) mutation, and response to NAC.
Methods
Patients aged below 65 years with high HRD or germline BRCA1/2 (gBRCA1/2) mutation randomly received paclitaxel + carboplatin (group A1) or eribulin + carboplatin (A2), followed by anthracycline. Patients aged below 65 years with low HRD or those aged 65 years or older without gBRCA1/2 mutation randomly received eribulin + cyclophosphamide (B1) or eribulin + capecitabine (B2); nonresponders to the first four cycles of the therapy received anthracycline. A pathological complete response (pCR) was defined as the absence of residual cancer cells in the tissues. Pretreatment biopsy specimens were stained by multiplexed fluorescent immunohistochemistry using antibodies against CD3, CD4, CD8, Foxp3, CD204, and pan-cytokeratin. Immune cells with specific phenotypes were counted per mm2 in cancer cell nests (intratumor) and stromal regions. The immune cell densities were compared with clinicopathological and genetic factors including tumor response.
Results
This study analyzed 66 samples. T1 tumors had a significantly higher density of intratumoral CD8+ T cells than T2 or larger tumors. The tBRCA1/2 mutation or HRD status was not associated with the density of any immune cell. The density of intratumoral and stromal CD4+ T cells was higher in patients showing pCR than in those without pCR. In a multivariate analysis, intratumoral and stromal CD4+ T cell density significantly predicted pCR independent of age, chemotherapy dose, HRD status, and treatment groups (P = 0.009 and 0.0057, respectively). In a subgroup analysis, the predictive value of intratumoral and stromal CD4+ T cell density persisted in the platinum-containing chemotherapy group (A1+A2) but not in the non-platinum-containing group (B1+B2).
Conclusions
Intratumoral and stromal CD4+ T cell density was an independent predictor of pCR in patients with TNBC. A larger study is warranted to confirm the results
A case study of heat recovery: a heat pump in an industrial site
Full text linkGreenhouse gases cause global warming of the earth. Carbon dioxide is one of those gases. There are different sources of carbon emission such as industrial activities and deforestation. The application of energy efficiency in industrial environment is one lever to reduce carbon emissions.
"Waste" heat represents a significant energy saving potential for industrial companies. Thanks to recovery technologies, waste heat resulting from a process that is not used by it can be recovered for other uses within the same plant or outside. In addition to the economic interest, the recovery of fatal heat is very virtuous from an ecological point of view if the recovered energy avoids the consumption of fossil fuel. It thus improves the carbon footprint of an industrial installation.
This article is a case study in an industrial pharmaceutical site in France and explains how a heat pump has been implemented. All the steps of the methodology are detailed: deep analysis of waste heat from the site, calculation and measurement of the reuse potential and research of the most suitable technology to carry out this recovery. This study has permits to reduce by 1/3 site’s carbon emissions
Intrinsic features of Zika Virus non-structural proteins NS2A and NS4A in the regulation of viral replication
Full text linkZika virus (ZIKV) is a mosquito-borne flavivirus and can cause neurodevelopmental disorders in fetus. As a neurotropic virus, ZIKV persistently infects neural tissues during pregnancy but the viral pathogenesis remains largely unknown. ZIKV has a positive-sense and single-stranded RNA genome, which encodes 7 non-structural (NS) proteins, participating in viral replication and dysregulation of host immunity. Like those in many other viruses, NS proteins are considered to be products evolutionarily beneficiary to viruses and some are virulence factors. However, we found that some NS proteins encoded by ZIKV genome appeared to function against the viral replication. In this report we showed that exogenously expressed ZIKV NS2A and NS4A inhibited ZIKV infection by inhibiting viral RNA replication in microglial cells and astrocytes. To understand how viral NS proteins suppressed viral replication, we analyzed the transcriptome of the microglial cells and astrocytes and found that expression of NS4A induced the upregulation of ISGs, including MX1/2, OAS1/2/3, IFITM1, IFIT1, IFI6, IFI27, ISG15 or BST2 through activating the ISGF3 signaling pathway. Upregulation of these ISGs seemed to be related to the inhibition of ZIKV replication, since the anti-ZIKV function of NS4A was partially attenuated when the cells were treated with Abrocitinib, an inhibitor of the ISGF3 signaling pathway, or were knocked down with STAT2. Aborting the protein expression of NS4A, but not its nucleic acid, eliminated the antiviral activity of NS4A effectively. Dynamic expression of viral NS proteins was examined in ZIKV-infected microglial cells and astrocytes, which showed comparatively NS4A occurred later than other NS proteins during the infection. We hypothesize that NS4A may possess intrinsic features to serve as a unique type of pathogen associated molecular pattern (PAMP), detectable by the cells to induce an innate immune response, or function with other mechanisms, to restrict the viral replication to a certain level as a negative feedback, which may help ZIKV maintain its persistent infection in fetal neural tissues