Differentiating Lyme arthritis: a case-based review.

The incidence or prevalence of Lyme arthritis (LA) in Denmark is unknown and assumed very low. No published cases of polymerase chain reaction (PCR)-confirmed LA from Denmark exist. Clinically, LA does not differ from other rheumatic oligoarthritic disorders posing a differential diagnostic challenge. To review the incidence and prevalence of LA to our knowledge and to present a case series of PCR-confirmed LA cases from Denmark. We conducted a systematic literature review via MEDLINE and EMBASE to explore incidence and prevalence rates of LA. Additionally, we present six cases of patients diagnosed with LA in Denmark. Our literature review identified 23 studies reporting prevalence or incidence, yet only ten studies provided estimates ranging from 1.1 to 280/100.000 in the general population. Our case series identified six patients with LA from a localized region in Southern Denmark; all confirmed by Borrelia-specific real-time PCR from synovial fluid. The diagnostic delay was up to 38 months. All patients except one had a history of previous tick bites; none had erythema migrans lesions. All presented with recurrent arthritis in the knee joint, and two had arthritis in the wrist. The literature review showed an incidence of LA ranging from 1.1 to 15.8 per 100.000 in Europe. Our case series suggests a potentially higher prevalence of LA in Denmark than previously believed. Lack of tick exposure history, antibody assessments and test of Borrelia burgdorferi sensu lato DNA in synovial fluid might lead to misdiagnosed cases potentially explaining the assumed low incidence of LA in Denmark.

The prognostic role of epidermal growth factor receptor mutation in completely resected ampullary adenocarcinoma.

The aim of this study is to make a differential diagnosis and prognosis of the ampullary adenocarcinoma subtypes. We also investigated the role of prognostic markers PD-1 and PD-L1, and epidermal growth factor receptor (EGFR). Local or locally advanced stage ampullary adenocarcinoma patients who had undergone pancreaticoduodenectomy at the time of diagnosis were included. MUC1, MUC2, MUC5AC, CDX2, CK7, CK20, PD-1, and PDL-1 were analysed immunohistochemically, and EGFR was analysed by real-time polymerase chain reaction. According to histopathological and immunohistochemical evaluation, we found 27 patients as pancreatobiliary type and 56 patients as intestinal type adenocarcinoma. The median survival of patients with intestinal and pancreatobiliary type adenocarcinoma was 23 months and 76 months ( p = 0.201), respectively. When the survival of PD1-positive ( n = 23) and PD-L1-positive ( n = 18) patients were compared with the patients with negative staining ( n = 60, n = 65), no significant difference was found. Epidermal growth factor receptor mutation was detected in a total of 6 patients, and 5 of these 6 mutations were shown in intestinal type tumours and one in a pancreatobiliary type tumour. A significant difference was determined in terms of overall survival for the patients with EGFR mutations compared to those without ( p = 0.008). In conclusion, we could reveal the prognostic significance of EGFR mutation, which is also a target molecule.

Changes in Kawasaki disease incidence and phenotype during the COVID-19 pandemic.

INTRODUCTION: The aetiology of Kawasaki disease (KD) remains unknown. Changes in infectious exposure during the COVID-19 pandemic owing to infection prevention measures may have affected the incidence of KD, supporting the pathogenic role of an infectious trigger. The purpose of this study was to evaluate the incidence, phenotype and outcome of KD before and during the COVID-19 pandemic in Denmark. METHODS: This was a retrospective cohort study based on patients diagnosed with KD at a Danish paediatric tertiary referral centre from 1 January 2008 to 1 September 2021. RESULTS: A total of 74 patients met the KD criteria of whom ten were observed during the COVID-19 pandemic in Denmark. All of these patients were negative for SARS-CoV-2 DNA and antibodies. A high KD incidence was observed during the first six months of the pandemic, but no patients were diagnosed during the following 12 months. Clinical KD criteria were equally met in both groups. The fraction of intravenous immunoglobulin (IVIG) non-responders was higher in the pandemic group (60%) than in the in the pre-pandemic group (28.3%), although the rate of timely administered IVIG treatment was the same in both groups (≥ 80%). Coronary artery dilation was observed in 21.9% in the pre-pandemic group compared with 0% in KD patients diagnosed during the pandemic. CONCLUSION: Changes in KD incidence and phenotype were seen during the COVID-19 pandemic. Patients diagnosed with KD during the pandemic had complete KD, higher liver transaminases and significant IVIG resistance but no coronary artery involvement. FUNDING: None. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency (DK-634228).

Utilization of olive mill wastewater for selective production of lipids and carotenoids by Rhodotorula glutinis.

Olive mill wastewater (OMW) is a zero-cost substrate for numerous value-added compounds. Although several studies on the production of lipids and carotenoids by Rhodotorula glutinis in OMW exist, none of them has specifically focused on the conditions for a target lipid or carotenoid. This study presents cultivation conditions that selectively stimulate the cell biomass, individual carotenoids and lipids. It was found that supplemental carbon and nitrogen sources as well as illumination affected cell biomass the most. High temperature, low initial pH, illumination, lack of urea and presence of glycerol stimulated the lipid synthesis. The highest total lipid content obtained in undiluted OMW supplemented with urea was 11.08 ± 0.17% (w/w) whilst it was 41.40 ± 0.21% (w/w) when supplemented with glycerol. Moreover, the main fatty acid produced by R. glutinis in all media was oleic acid, whose fraction reached 63.94 ± 0.58%. Total carotenoid yield was significantly increased with low initial pH, high temperature, illumination, certain amounts of urea, glycerol and cultivation time. Up to 192.09 ± 0.16 µg/g cell carotenoid yield was achieved. Torularhodin could be selectively produced at high pH, low temperature and with urea and glycerol supplementation. To selectively induce torulene synthesis, cultivation conditions should have low pH, high temperature and illumination. In addition, low pH, high temperature and urea supplementation served high production of ß-carotene. Up to 85.40 ± 0.76, 80.67 ± 1.40 and 39.45 ± 0.69% of torulene, torularhodin and ß-carotene, respectively, were obtained under selected conditions. KEY POINTS: • Cultivation conditions selectively induced target carotenoids and lipids • 41.40 ± 0.21% (w/w) lipid content and 192.09 ± 0.16 µg/g cell carotenoid yield were achieved • Markedly high selectivity values for torularhodin and torulene were achieved.

Comparative phytochemical studies on the roots of Polygala azizsancarii and P. peshmenii and neuroprotective activities of the two xanthones.

Six known sucrose mono-, di- and triesters and five xanthone derivatives were isolated from the roots of Polygala peshmenii Eren, Parolly, Raus & Kürschner which is a narrow species endemic to Türkiye. Among the xanthones, 1,7-dihydroxy-2,3-methylenedioxy-5,6-dimethoxy-xanthone is an undescribed compound isolated for the first time from a natural source. The studies on the roots of P. azizsancarii Dönmez have resulted in the isolation of four known compounds including sucrose mono-, di- and triesters. The structures of the sucrose esters and xanthones isolated from P. azizsancarii and P. peshmenii were established by spectroscopic methods, including 1D-NMR (1H NMR, 13C NMR, DEPT-135), 2D-NMR (COSY, NOESY, HSQC, HMBC). Neuroprotective activities of two xanthones, 1,3,6-trihydroxy-2,5,7-trimethoxyxanthone and 3-O-ß-D-glucopyranosyloxy-1,6-dihydroxy-2,5,7-trimethoxyxanthone isolated from the roots of P. azizsancarii were evaluated in vitro using in a cellular model of Alzheimer's disease. SKNAS human neuroblastoma cells were used in the study and treated with different consecrations of Aß25₋35 oligomer for up to 48 h. Cell viability was evaluated using MTT assay. The distribution of ß-amyloid, α-synuclein, tau, JAK2, STAT3, caspase 3 and BMP-2 were investigated using indirect immunoperoxidase staining. Our results suggested that both xanthones control tau aggregation with no effect on ß-amyloid plaque formation. In addition, for neuronal pathophysiology in AD cell model, decreased distributions of JAK/STAT3 and BMP2 signaling pathways were demonstrated, therefore they play a role in the protective effect on neurons in neurodegenerative disease. A significant decrease in caspase 3 immunoreactivity was detected after the administration of both compounds in AD cells. Therefore, both compounds control neuronal pathophysiology and rescue cell death in AD disease.

Xanthones and Xanthone O-ß-D-Glucosides from the Roots of Polygala azizsancarii Dönmez.

Nine xanthone derivatives (1-9) were isolated from the roots of Polygala azizsancarii, which is a narrow endemic species for the flora of Türkiye. Based on all of the evidence, the structures of 1-9 were established as two previously undescribed xanthone O-glucosides, 3-O-ß-D-glucopyranosyloxy-1,6-dihydroxy-2,5,7-trimethoxyxanthone (1), 3-O-ß-D-glucopyranosyloxy-1,6-dihydroxy-2,7-dimethoxyxanthone (2), and seven previously described xanthones, 1,3,6-trihydroxy-2,5,7-trimethoxyxanthone (3), 1,3,6-trihydroxy-2,7-dimethoxyxanthone (4), 1,2,3,4,7-pentamethoxyxanthone (5), 1,3-dihydroxy-2,5,6,7-tetramethoxyxanthone (6), 1,3-dihydroxy-4,7-dimethoxyxanthone (7), 1,7-dihydroxy-3-methoxyxanthone (8), and 1,7-dihydroxy-2,3-methylenedioxyxanthone (9). The structures of the compounds were determined by spectroscopic methods, including 1D-NMR (1 H-NMR, 13 C-NMR, DEPT-135), 2D-NMR (COSY, NOESY, HSQC, HMBC, INADEQUATE), and HR-MS. The solid-state structures of 1-4, including the absolute configurations of the stereogenic carbons of the sugar moiety in 1 and 2, were established by X-ray crystal-structure analyses. For the newly described compounds, the trivial names sancarosides A (1) and B (2) are proposed.

Isolation, Characterization and In Silico Studies of Secondary Metabolites from the Whole Plant of Polygala inexpectata Pesmen & Erik.

Polygala species are frequently used worldwide in the treatment of various diseases, such as inflammatory and autoimmune disorders as well as metabolic and neurodegenerative diseases, due to the large number of secondary metabolites they contain. The present study was performed on Polygala inexpectata, which is a narrow endemic species for the flora of Turkey, and resulted in the isolation of nine known compounds, 6,3'-disinapoyl-sucrose (1), 6-O-sinapoyl,3'-O-trimethoxy-cinnamoyl-sucrose (tenuifoliside C) (2), 3'-O-(O-methyl-feruloyl)-sucrose (3), 3'-O-(sinapoyl)-sucrose (4), 3'-O-trimethoxy-cinnamoyl-sucrose (glomeratose) (5), 3'-O-feruloyl-sucrose (sibiricose A5) (6), sinapyl alcohol 4-O-glucoside (syringin or eleutheroside B) (7), liriodendrin (8), and 7,4'-di-O-methylquercetin-3-O-ß-rutinoside (ombuin 3-O-rutinoside or ombuoside) (9). The structures of the compounds were determined by the spectroscopic methods including 1D-NMR (1H NMR, 13C NMR, DEPT-135), 2D-NMR (COSY, NOESY, HSQC, HMBC), and HRMS. The isolated compounds were shown in an in silico setting to be accommodated well within the inhibitor-binding pockets of myeloperoxidase and inducible nitric oxide synthase and anchored mainly through hydrogen-bonding interactions and π-effects. It is therefore plausible to suggest that the previously established anti-inflammatory properties of some Polygala-derived phytochemicals may be due, in part, to the modulation of pro-inflammatory enzyme activities.

Effects of Methyl Salicylate on Host Plant Acceptance and Feeding by the Aphid Rhopalosiphum padi.

Methyl salicylate (MeSA) is a volatile shown to act as an inducer of plant defense against pathogens and certain herbivores, particularly aphids. It has been shown to have potential for aphid pest management, but knowledge on its mode of action is lacking, particularly induced plant-mediated effects. This study investigated the effects of exposing plants to MeSA on the host searching, host acceptance and feeding behavior of the bird cherry-oat aphid Rhopalosiphum padi. Barley plants were exposed to volatile MeSA for 24 h, after which biological effects were tested immediately after the exposure (Day 0), and then 1, 3 and 5 days after the end of the exposure. Aphid settling on MeSA-exposed plants was significantly reduced on days 0, 1 and 3, but not on day 5. In olfactometer tests, aphids preferred the odor of unexposed plants on days 1 and 3, but not on day 0 or 5. Analysis of volatiles from exposed and unexposed plants showed higher levels of MeSA from exposed plants, most likely absorbed and re-released from plant surfaces, but also specific changes in other plant volatiles on days 0, 1 and 3. High doses of MeSA did not affect aphid orientation in an olfactometer, but lower doses were repellent. Analysis of aphid feeding by Electronic penetration graph (EPG) showed that MeSA exposure resulted in resistance factors in barley plants, including surface factors and induced systemic factors in other tissues including the phloem. The results support the potential of MeSA as a potential tool for management of aphid pests.

Effect of Humic Acid on Oxidative Stress and Neuroprotection in Traumatic Spinal Cord Injury: An Experimental Study.

OBJECTIVE: Traumatic spinal cord injury (TSCI) is an important health problem especially in developing countries with additional socio-economic loss. Humic acids (HA) usually have anti-oxidant, anti-inflammatory, blood-circulating and antiviral effects. We aimed to show effect of HA on neuroprotection in TSCI model. METHODS: We performed TSCI model in Twenty-four Wistar-Albino rats in four groups. Control group underwent only laminectomy. Sham group underwent laminectomy followed by TSCI. Low dose HA (5mg/kg) and high dose HA (10mg/kg) groups underwent laminectomy and TSCI followed by peritoneal administration of HA. Preoperative, postoperative 1st hour and postoperative 24th hour cardiac blood samples were obtained. Total Antioxidant Status (TAS), Total Oxidant Status (TOS) and Oxidative Index (OI) levels were evaluated in serum. The 24th hour motor functions were evaluated by Modified Tarlov Score. RESULTS: There were no significant changes in TAS values between sham- low dose and high dose humic acid groups (p:0.77/0.21). However there were a significant decrease of TOS levels in the 24th hour post operative blood samples comparing the sham group with low dose humic acid group (p=0.02). Pathological evaluation showed a significant decrease in the severity of edema, hemorrhage, Polymorphonuclear leucocytes (PNL) and Mononuclearleucocytes (MNL) /macrophage/microglia when we compare with the control group (p<0.05). There is a significant recovery in paraplegia level as we compared the HA groups with control groups (p<0.001). CONCLUSION: In this study, we showed the effects of HA in the early stages of TSCI on oxidative stress, histopathological changes and neurological improvement. It is thought to be a potential therapeutic agent in acute TSCI but needs to be further evaluated by showing proper effect on other neuroprotective pathways in larger series.

Green and Non-conventional Extraction of Bioactive Compounds from Olive Leaves: Screening of Novel Natural Deep Eutectic Solvents and Investigation of Process Parameters.

ABSTRACT: Olive leaf as an agricultural waste contains valuable bioactive compounds that are mainly used for pharmaceutical and cosmetic industries. Lately the major component, oleuropein, has gained extra attention due to the anti-viral activity against SARS-CoV-2 that causes Coronavirus disease (Covid-19). In this study, extraction of the bioactive compounds from olive leaves was conducted using a non-conventional and green method. New generation green solvents, natural deep eutectic solvents (NADES) were used in combination with ultrasound assisted extraction. Screening of NADES type, temperature, and particle size were investigated using one-pot-at-a-time method while, NADES amount and liquid-to-solid ratio were optimized using experimental design. The results were evaluated in terms of total polyphenol yield (YTP), total flavonoid yield (YTF) and antiradical activity (AAR). At the optimized conditions, the highest total polyphenol yield and the highest total flavonoid yield were achieved with choline chloride-fructose-water (CFW) (5:2:5) as 187.31 ± 10.3 mg gallic acid equivalent g-1 dw and 12.75 ± 0.6 mg apigenin equivalent g-1 dw, respectively. The extracts were also analyzed for oleuropein, caffeic acid and luteolin contents. The highest amount of oleuropein and caffeic acid were extracted by glucose-fructose-water (GFW) (1:1:11) as 1630.80 mg kg-1 dw and 112.77 mg kg-1 dw, respectively. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s12649-021-01411-3) contains supplementary material, which is available to authorized users.

Comparison of native and non-native predator consumption rates and prey avoidance behavior in North America and Europe.

Novel predator-prey interactions can contribute to the invasion success of non-native predators. For example, native prey can fail to recognize and avoid non-native predators due to a lack of co-evolutionary history and cue dissimilarity with native predators. This might result in a competitive advantage for non-native predators. Numerous lady beetle species were globally redistributed as biological control agents against aphids, resulting in novel predator-prey interactions. Here, we investigated the strength of avoidance behavior of the pea aphid (Acyrthosiphon pisum) toward chemical cues of native lady beetles and non-native Asian Harmonia axyridis and European Coccinella septempunctata and Hippodamia variegata in North America, hypothesizing that cues of non-native lady beetles induce weaker avoidance behavior than cues of co-evolved native lady beetles. Additionally, we compared aphid consumption of lady beetles, examining potential predation advantages of non-native lady beetles. Finally, we compared cue avoidance behavior between North American and European pea aphid populations and aphid consumption of native and non-native lady beetles in North America and Europe. In North America, pea aphids avoided chemical cues of all ladybeetle species tested, regardless of their origin. In contrast to pea aphids in North America, European pea aphids did not avoid cues of the non-native H. axyridis. The non-native H. axyridis and C. septempunctata were among the largest and most voracious lady beetle species tested, on both continents. Consequently, in North America non-native lady beetle species might have a competitive advantage on shared food resources due to their relatively large body size, compared to several native American lady beetle species. In Europe, however, non-native H. axyridis might benefit from missing aphid cue avoidance as well as a large body size. The co-evolutionary time gap between the European and North American invasion of H. axyridis likely explains the intercontinental differences in cue avoidance behavior and might indicate evolution in aphids toward non-native predators.

Does the ACR TI-RADS scoring allow us to safely avoid unnecessary thyroid biopsy? single center analysis in a large cohort.

INTRODUCTION: The American College of Radiology (ACR) has recently proposed a guideline that recommends clinicians to perform thyroid fine-needle aspiration biopsy (FNAB) on the basis of ultrasound features. In this study, we focused on nodules for which no biopsy is recommended by the ACR Thyroid Imaging, Reporting and Data System (TI-RADS) guideline. SUBJECTS AND METHODS: Two-thousand eight-hundred and forty-seven consecutive patients with thyroid nodules who underwent FNAB according to the 2009 American Thyroid Association (ATA) guideline were included. The nodules were re-classified according to the ACR TI-RADS guideline as benign (TR1), not suspicious (TR2), mildly suspicious (TR3), moderately suspicious (TR4) and highly suspicious (TR5). The TR3 category was stratified into two subcategories as regard to the nodule size (TR3; <25 mm and TR3; ≥25 mm). RESULTS: Two-hundred and thirty-three (8.2%) patients with non-diagnostic FNABs were excluded. When the TR2 and TR3; <25 mm categories were merged, FNAB was suggestive of thyroid cancer in 17 of 1382 patients (1.2%). FNAB revealed Bethesda IV-VI in 5 of 273 patients with the TR3; ≥25 mm category (1.8%), in 61 of 896 patients with the TR4 category (6.8%), and in 18 of 63 of patients with the TR5 category (28.6%). The ACR TI-RADS scoring was 98.8% (95% CI: 98 to 99.3) specific for identification of a benign nodule. CONCLUSION: Our data suggest that ACR TI-RADS scoring is an applicable and potentially cost-effective approach to determine thyroid nodules to be biopsied, although a small proportion of thyroid cancers would be missed.

Investigation of a green process for the polymerization of catechin.

Flavonoids are polyphenolic secondary plant metabolites which possess antioxidant and anti-inflammatory properties. Besides, they have been shown to exhibit increased antioxidant properties in their polymerized form. Catechins are one of the attractive class of flavonoids which belong to the group of flavan-3-ols. Polymerization of catechins have been investigated in numerous studies indicating the requirement of certain amount of organic solvent to provide the solubility of the monomer. However, many research projects have been conducted recently to replace toxic organic contaminants of the processes with environmentally friendly solvents. In this aspect, deep eutectic solvents (DESs) that are regarded as "green solvents" have been studied extensively in various enzyme catalyzed reactions. In the present study, we focused on establishing a green pathway for laccase catalyzed polycatechin synthesis by replacing organic solvent content with DESs as green solvents. For this aim, various parameters were investigated, such as DES types and concentrations laccase amount and reaction time. Consequently, the highest molecular weight polycatechin was obtained using 5% (v/v) B-M, 125 U laccase in 1 hr of reaction time, at 30°C, as 4,354 ± 678 g mol-1. Corresponding X/XO inhibitory activity and superoxide radical scavenging activities were achieved as, 59 and 50%, respectively.

Investigation of the simultaneous production of superoxide dismutase and catalase enzymes from Rhodotorula glutinis under different culture conditions.

The simultaneous production production of superoxide (SOD) and catalase (CAT) from Rhodotorula glutinis was studied. The effects of temperature, initial medium pH, and carbon source on the enzyme activities were investigated. Temperature and carbon sources were found to have significant effects on the enzyme activities. 10°C provided the highest specific CAT and SOD activities as 22.6 U/mg protein and 170 U/mg protein, respectively. Glycerol was found to be the best carbon source for enzyme activities, providing 113 U/mg protein for CAT and 125 U/mg protein for SOD, which were also the highest activities obtained in the present study.

Effects of alcohol and buffer treatments on the activity and enantioselectivity of Candida rugosa lipase.

Several treatments were employed on Candida rugosa lipase (CRL) to improve its biocatalytic performance. Besides conventional alcohol treatment conditions, the effects of pH of the buffer solution used in the treatment as well as the changes in stirring, dialysis, and centrifugation steps of the treatment procedure were investigated for the first time for the resolution of racemic naproxen methyl ester. The highest enantioselectivity and conversion in S-naproxen production were achieved by CRL treated with pH 7.5 buffer solution. The elimination of the centrifugation step resulted in an increase in the enantioselectivity, whereas alcohol treatment of CRL was found to be inconvenient for S-naproxen production. Higher activity for p-nitrophenyl acetate was achieved when 20% butanol and pH 4 buffer solution were used, and when dialysis and stirring times were shortened.