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Many species of Thymus have been widely used in Algerian folk medicine as astringent, expectorant and cicatrising agents. This study was designed to investigate for the first time the essential oil of the aerial parts of wild growing Thymus algeriensis endemic in North Africa. The volatiLe oil obtained by hydrodistillation was characterized by the physico-chemical properties, GC and GC/MS techniques. The yield of the oil was 1.13% (w/w), based on dry weight. Fifty-five components, representing 94.3% of the total oil, were identified. The oil was distinguished by its high content of oxygenated monoterpenes (79.5%) and was found to possess the following major components: linalool (47.3%), thymol (29.2%) and p-cymene (6.8%). Furthermore, the oil was tested for antimicrobial activity against four bacteria, two fungi and two yeasts. This oil exhibited a significant in vitro antimicrobial activity against Bacillus subtilis (MIC = 0.5 [micro]L/mL), as well as against all yeast and all filamentous fungi tested (MIC = 0.5 and 1.0 [micro]L/mL). KEYWORDS Thymus algeriensis; Essential oil; Linalool; Thymol; p-cymene; Antimicrobial activity

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The yield of oil isolated by hydrodistillation from aerial parts of Thymus fontanesii Boiss. et Reut. (Lamiaceae) growing wild in Djelfa (Algeria) was 0.9%. Analysis of the oil by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) revealed the identification of 47 components accounting for 98.5% of the total oil. The oil was found to be rich in monoterpenes (91.5%) with major constituents being thymol (29.3%), γ-terpinene (21.7%), p-cymene (15.9%), and thymol methyl ether (11.4%), while a smaller amount of linalool (4.8%) and β-caryophyllene (2.9%) were detected. According to the antimicrobial study using the disk diffusion method and the agar dilution assay–minimal inhibitory concentration (MIC), the oil showed strong in vitro growth inhibition activity against Gram-negative bacteria and antifungal activity. The oil exhibited the maximum antifungal activity against Mucor ramaniamus (MIC = 0.2 µL/mL). [ABSTRACT FROM AUTHOR]

The essential oil of Lavandula stoechas L. growing spontaneously in Algeria was investigated by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) for the first time. The oil was isolated from the aerial parts of the plant (leaves and flowers) by distillation in a yield of 1.1%. Fifty-four components amounting to ca . 73% of the oil were identified, the major component being fenchone (31.6%). The other significant constituents were camphor (22.4%), p -cymene (6.5%), lavandulyl acetate (3.0%), and a-pinene (1.0%). Our results show that the oil consists mainly of oxygenated monoterpenes (62.0%). A comparison with oils from other Lavandula stoechas from other countries reported in literature shows qualitative and quantitative differences. [ABSTRACT FROM AUTHOR]

The chemical composition of the essential oil of Juniperus oxycedrus from Algeria was studied for the first time. The oil was obtained from the leaves of the plant by hydrodistillation and analyzed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) techniques. The yield of essential oil is 0.1%, based on dry weight. Eighty-nine components representing 82.3% of the total oil were identified. The results show that oxygenated monoterpene (41.0%) composes the major part of oil and the main components are trans -pinocarveol (7.0%), cis -verbenol (6.3%), and manoyl oxide (6.0%). A comparison with oils from J. oxycedrus complex (subspecies and varieties) of other countries reported in literature is discussed briefly. [ABSTRACT FROM AUTHOR]

The chemical composition of the hydrodistilled essential oil of the air-dried aerial parts of wild red wormwood ( Artemisia campestris L.) was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The species is poor in essential oil (yield = 0.1%). Seventy-one constituents representing 57.0% of total oil have been identified. The result show that oxygenated compounds compose the major part of oil (43.7%) and the main components are ( Z,E )-farnesol (10.3%) followed by cedrol (5.4%) and verbenone (3.8%). Toxic ketones such as α- and β-thujone are not detected in the oil. [ABSTRACT FROM AUTHOR]

Presents research which studied reasons for the absence of long-term efficacy of mycophenolate mofetil (MMF). Common use of MMF for baseline immunosuppression; Methods; Comparison of long-term MMF patients with short-term in trough plasma concentration of mycophenolic acid (MPA); How MMF acts; Possible modification of the pharmacokinetic behavior of MMF; Recommendations.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

The ability to track altered enzyme activity using a non-invasive imaging protocol is crucial for the early diagnosis of many diseases but is often challenging. Herein, we show that Overhauser magnetic resonance imaging (OMRI) can be used to monitor enzymatic conversion at an ultra-low field (206 μT) using a highly sensitive "off/on" probe with a nitroxide stable radical containing ester, named T2C 12 -T80. This TEMPO derivative containing probe forms stable electron paramagnetic resonance (EPR) silent micelles in water that are hydrolysed by esterases, thus yielding narrow EPR signals whose intensities correlate directly with specific enzymatic activity. The responsiveness of the probe to tumours, facilitated by increased esterase activity, was initially determined by comparing EPR signals measured upon incubation with 3T3 (healthy fibroblasts used as control), HepG2 (human hepatoma) and Hs766T (human pancreatic cancer cells) cell lysates and then with Hs766T and 3T3 living cells. Next, Overhauser MR images were detected on a phantom containing the probe and the esterases to show that the approach is well suited for being translated to the in vivo detection at the earth's magnetic field. Regarding detection sensitivity, ultra-low field OMRI (ULF-OMRI) is beneficial over OMRI at higher fields ( e.g. 0.2 T) since Overhauser enhancements are significantly higher and the technique is safe in terms of the specific absorption rate.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: This study aimed to assess the overall survival (OS) of patients after high-grade glioma (HGG) resection and to search for associated prognostic factors., Methods: A random sample of ad hoc cases was extracted from the French medico-administrative national database, Système National des Données de Santé (SNDS). We solely considered the patients who received chemoradiotherapy with temozolomide (TMZ/RT) after HGG surgery. Statistical survival methods were implemented., Results: A total of 1,438 patients who had HGG resection at 58 different institutions between 2008 and 2019 were identified. Of these, 34.8% were female, and the median age at HGG resection was 63.2 years (interquartile range [IQR], 55.6-69.4 years). Median OS was 1.69 years (95% confidence interval [CI], 1.63-1.76), i.e., 20.4 months. Median age at death was 65.5 years (IQR, 58.5-71.8). OS at 1, 2, and 5 years was 78.5% (95% CI, 76.4-80.7), 40.3% (95% CI, 37.9-43), and 11.8% (95% CI, 10.2-13.6), respectively. In the adjusted Cox regression, female gender (HR=0.71; 95% CI, 0.63-0.79; p <0.001), age at HGG surgery (HR=1.02; 95% CI, 1.02-1.03; p <0.001), TMZ treatment over 6 months after HGG surgery (HR=0.36; 95% CI, 0.32-0.4; p <0.001), bevacizumab (HR=1.22; 95% CI, 1.09-1.37; p <0.001), and redo surgery (HR=0.79; 95% CI, 0.67-0.93; p =0.005) remained significantly associated with the outcome., Conclusion: The SNDS is a reliable source for studying the outcome of HGG patients. OS is better in younger patient, female gender, and those who complete concomitant chemoradiotherapy. Redo surgery for HGG recurrence was also associated with prolonged survival., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Korean Brain Tumor Society, The Korean Society for Neuro-Oncology, and The Korean Society for Pediatric Neuro-Oncology.)

Langerhans histiocytosis or histiocytosis X is an oligo-clonal proliferation of Langerhans cells. We report the case of an 11-month-old infant who had presented with a parieto-occipital swelling since birth, which progressively increased in volume without any other presenting signs. The radiological work-up initially suspected osteitis of the vault, which was removed in its entirety. The anatomopathological study concluded that it was histiocytosis X. The extension work-up was negative. Follow-up of this patient showed no local recurrence or appearance of other localizations. A review of the literature shows that little is known about its pathophysiology. It mainly affects children and young adults. There are several possible sites of involvement, and cranial vault involvement is a fairly frequent form among the bony sites of this pathology. The diagnosis is confirmed histologically or cytologically, and extension workup is required to confirm the diagnosis. Therapeutic management has not been standardized, and sometimes requires chemotherapy in addition to surgery. The prognosis depends on whether vital organs are affected or not., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor responses remains unclear. Here, we show that patients with metastatic lung adenocarcinoma harbouring co-mutations of EGFR and TP53, are more likely to have mixed intra-patient tumor responses to EGFR tyrosine kinase inhibition (TKI), compared to those with an EGFR mutation alone. The combined presence of whole genome doubling (WGD) and TP53 co-mutations leads to increased genome instability and genomic copy number aberrations in genes implicated in EGFR TKI resistance. Using mouse models and an in vitro isogenic p53-mutant model system, we provide evidence that WGD provides diverse routes to drug resistance by increasing the probability of acquiring copy-number gains or losses relative to non-WGD cells. These data provide a molecular basis for mixed tumor responses to targeted therapy, within an individual patient, with implications for therapeutic strategies., (© 2024. The Author(s).)

Diabetes mellitus is a chronic metabolic disease characterized by persistent hyperglycemia, revealing a decrease in insulin efficiency. The sustained glucotoxic pancreatic microenvironment increases reactive oxygen species generation, resulting in chronic oxidative stress responsible for massive DNA damage. This triggers PARP-1 activation with both NAD + and ATP depletion, affecting drastically pancreatic beta cells' energy storage and leading to their dysfunction and death. The aim of the present study is to highlight the main histological changes observed in pancreatic islets pre-treated with a unique NADH intraperitoneal injection in a streptozotocin-(STZ)-induced diabetes model. In order to adjust NADH doses, a preliminary study with three different doses, 500 mg/kg, 300 mg/kg, and 150 mg/kg, respectively, was conducted. Subsequently, and on the basis of the results of the aforementioned study, Wistar rats were randomly divided into four groups: non-diabetic control group, diabetics (STZ 45 mg/kg), NADH-treated group (150 mg/kg) 15 min before STZ administration, and NADH-treated group (150 mg/kg) 15 min after STZ administration. The effect of NADH was assessed by blood glucose level, TUNEL staining, histo-morphological analysis, and immunohistochemistry. The optimum protective dose of NADH was 150 mg/kg. NADH effectively decreased hyperglycemia and reduced diabetes induced by STZ. Histologically, NADH pre-treatment revealed a decrease in beta cell death favoring apoptosis over necrosis and therefore preventing inflammation with further beta cell destruction. Our data clearly demonstrate that NADH prior or post-treatment could effectively prevent the deleterious loss of beta cell mass in STZ-induced diabetes in rats and preserve the normal pancreatic islet's function., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Grade 4 astrocytomas are usually incurable due to their diffusely infiltrative nature. Photodynamic therapy (PDT) is a promising therapeutic option, but external light delivery is impractical when cancer cells infiltrate unknown areas of normal brain. Hence the search for endogenous sources to generate light at cancer cells. In vitro, astrocytoma cells, transfected with firefly luciferase, can be killed by bioluminescence-mediated PDT (bPDT). This study asks if bPDT can suppress tumour growth In vivo, when all components of treatment are administered systemically., Methods: Transfected astrocytoma cells were injected subcutaneously or intra-cranially in athymic CD1 nu/nu mice. bPDT required ip bolus of mTHPC (photosensitiser) and delivery of the d-luciferin substrate over 7 days via an implanted osmotic pump. Control animals had no treatment, photosensitiser only or d-luciferin only. For subcutaneous tumours, size and BLI (light emitted after d-luciferin bolus) were measured before and every 2 days after PDT. For intracranial tumours, monitoring was weekly BLI., Results: For subcutaneous tumours, there was significant suppression of the tumour growth rate (P<0.05), and absolute tumour size (P<0.01) after bPDT. Proliferation of subcutaneous and intracranial tumours (monitored by BrdU uptake) was significantly reduced in treated mice. (P<0.001) CONCLUSIONS: This study reports bPDT suppression of tumour growth from luciferase transfected astrocytoma cells with all components of treatment given systemically, as required for effective management of recurrent astrocytomas in unknown sites. However, research on systemic bPDT is needed to establish whether effects on non-transfected tumours can be achieved without any unacceptable effects on normal tissues., Competing Interests: Declaration of Competing Interests None., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Development of very-low field MRI is an active area of research. It aims at reducing operating costs and improve portability. However, the signal-to-noise issue becomes prominent at ultra-low field (<1 mT), especially for molecular imaging purposes that addresses specific biochemical events. In the context of preclinical molecular MRI of abnormal proteolysis the paper describes a MRI system able to produce Overhauser-enhanced MR images in living rats through in situ Dynamic Nuclear Polarization at 206 µT using stable and non-toxic nitroxides. In parallel conventional images are generated at 206 µT following pre-polarization at 20 mT. Results show that nitroxides are visualized in 3D within a few minutes in the lungs, kidneys and bladder post-administration. This system will be used for molecular imaging of inflammation using protease-specific nitroxide probes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background & Aims: Dysplasia in Barrett's esophagus often is invisible on high-resolution white-light endoscopy (HRWLE). We compared the diagnostic accuracy for inconspicuous dysplasia of the combination of autofluorescence imaging (AFI)-guided probe-based confocal laser endomicroscopy (pCLE) and molecular biomarkers vs HRWLE with Seattle protocol biopsies., Methods: Barrett's esophagus patients with no dysplastic lesions were block-randomized to standard endoscopy (HRWLE with the Seattle protocol) or AFI-guided pCLE with targeted biopsies for molecular biomarkers (p53 and cyclin A by immunohistochemistry; aneuploidy by image cytometry), with crossover to the other arm after 6 to 12 weeks. The primary end point was the histologic diagnosis from all study biopsies (trial histology). A sensitivity analysis was performed for overall histology, which included diagnoses within 12 months from the first study endoscopy. Endoscopists were blinded to the referral endoscopy and histology results. The primary outcome was diagnostic accuracy for dysplasia by real-time pCLE vs HRWLE biopsies., Results: Of 154 patients recruited, 134 completed both arms. In the primary outcome analysis (trial histology analysis), AFI-guided pCLE had similar sensitivity for dysplasia compared with standard endoscopy (74.3%; 95% CI, 56.7-87.5 vs 80.0%; 95% CI, 63.1-91.6; P = .48). Multivariate logistic regression showed pCLE optical dysplasia, aberrant p53, and aneuploidy had the strongest correlation with dysplasia (secondary outcome). This 3-biomarker panel had higher sensitivity for any grade of dysplasia than the Seattle protocol (81.5% vs 51.9%; P &lt; .001) in the overall histology analysis, but not in the trial histology analysis (91.4% vs 80.0%; P = .16), with an area under the receiver operating curve of 0.83., Conclusions: Seattle protocol biopsies miss dysplasia in approximately half of patients with inconspicuous neoplasia. AFI-guided pCLE has similar accuracy to the current gold standard. The addition of molecular biomarkers could improve diagnostic accuracy., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Central conventional chondrosarcoma (CS) is the most common subtype of primary malignant bone tumour in adults. Treatment options are usually limited to surgery, and prognosis is challenging. These tumours are characterised by the presence and absence of IDH1 and IDH2 mutations, and recently, TERT promoter alterations have been reported in around 20% of cases. The effect of these mutations on clinical outcome remains unclear. The purpose of this study was to determine if prognostic accuracy can be improved by the addition of genomic data, and specifically by examination of IDH1, IDH2, and TERT mutations., Methods: In this study, we combined both archival samples and data sourced from the Genomics England 100,000 Genomes Project (n = 356). Mutations in IDH1, IDH2, and TERT were profiled using digital droplet PCR (n = 346), whole genome sequencing (n=68), or both (n = 64). Complex events and other genetic features were also examined, along with methylation array data (n = 84). We correlated clinical features and patient outcomes with our genetic findings., Results: IDH2-mutant tumours occur in older patients and commonly present with high-grade or dedifferentiated disease. Notably, TERT mutations occur most frequently in IDH2-mutant tumours, although have no effect on survival in this group. In contrast, TERT mutations are rarer in IDH1-mutant tumours, yet they are associated with a less favourable outcome in this group. We also found that methylation profiles distinguish IDH1- from IDH2-mutant tumours. IDH wild-type tumours rarely exhibit TERT mutations and tend to be diagnosed in a younger population than those with tumours harbouring IDH1 and IDH2 mutations. A major genetic feature of this group is haploidisation and subsequent genome doubling. These tumours evolve less frequently to dedifferentiated disease and therefore constitute a lower risk group., Conclusions: Tumours with IDH1 or IDH2 mutations or those that are IDHwt have significantly different genetic pathways and outcomes in relation to TERT mutation. Diagnostic testing for IDH1, IDH2, and TERT mutations could therefore help to guide clinical monitoring and prognostication., (© 2022. The Author(s).)

Background and Objectives: After two doses of mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients on dialysis show a defective humoral response, but a third dose could increase anti-SARS-CoV-2 spike IgG titers. Responses could be different in virus-naive and SARS-CoV-2-recovered patients on dialysis. However, characterization of memory B cell response after three doses is lacking., Design, Setting, Participants, & Measurements: We evaluated the dynamics of antireceptor binding domain IgG titers and antireceptor binding domain memory B cells until 6 months after two and three doses (administered within 6 months after the second dose) of mRNA vaccine in SARS-CoV-2-recovered and virus-naive dialysis populations. Results were analyzed by ordinary one-way ANOVA, the Kruskal-Wallis test, or the Wilcoxon matched-pairs test as appropriate., Results: In total, 108 individuals (59 patients on dialysis and 49 controls) were included. In virus-naive patients on dialysis, antireceptor binding domain IgG response was quantitatively lower after two doses compared with healthy controls, but IgG titers increased by three-fold after three doses ( P =0.008). In SARS-CoV-2-recovered patients on dialysis, antireceptor binding domain IgG titers after two doses were significantly higher compared with virus-naive patients on dialysis but did not significantly increase after a third dose. Regarding memory B cell response, we detected receptor binding domain-specific memory B cells at similar proportions in virus-naive patients on dialysis and vaccinated controls after two doses. Moreover, a strong receptor binding domain-specific memory B cell expansion was observed after the third dose in virus-naive patients on dialysis (5.5-fold; P <0.001). However, in SARS-CoV-2-recovered patients on dialysis, antireceptor binding domain memory B cells remained unchanged after the third dose., Conclusions: The third dose of mRNA vaccine given within 6 months after the second dose boosts serologic and memory response in virus-naive patients but not in SARS-CoV-2-recovered patients on dialysis., Clinical Trial Registry Name and Registration Number: COVID-19: SARS-CoV-2 Specific Memory B and T-CD4+ Cells (MEMO-COV2), NCT04402892., (Copyright © 2022 by the American Society of Nephrology.)

The COVID-19 pandemic has been a global phenomenon defined by uncertainty, fear and grief which has resulted in record high levels of stress and anxiety in the first half of 2020. It also led to an increased interest in the study of the role of belief, religion, and spirituality as responses to coping with and responding to the pandemic throughout different societal domains. This study explores the impact of anxiety and stress caused by the pandemic on Muslim academics' subjective well-being. It also explores correlations between coping and spirituality by assessing Muslim academics' coping strategies in overcoming stress and anxiety. To this end, this study sampled 480 Muslim academics ages 25-60 years residing in Muslim countries. The findings show a negative yet significant correlation between anxiety and well-being while also showing a positive and significant correlation between coping strategies and subjective well-being. The research also points to the role of coping strategies in reducing anxiety and stress, the resulting improvements in well-being for Muslim academics, and the mediating effect of coping strategies between anxiety, stress, and well-being for Muslim academics., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Maintenance haemodialysis (MHD) patients have a high risk of initial mortality from coronavirus disease 2019 (COVID-19). However, long-term consequences of this disease in the MHD population are poorly described. We report the clinical presentation, outcome and long-term follow-up of MHD patients affected by COVID-19 in a multicentric cohort from the Paris, France area., Methods: We conducted a retrospective analysis of clinical presentation and long-term follow-up of MHD patients affected by COVID-19 in 19 MHD centres in the Paris, France area., Results: In this cohort of 248 patients with an initial mortality rate of 18%, age, comorbidities, dyspnoea and previous immunosuppressive treatment were associated with death at <30 days. Among the 203 surviving patients following the acute phase, long-term follow-up (median 180 days) was available for 189 (93%) patients. Major adverse events occurred in 30 (16%) patients during follow-up, including 12 deaths (6%) after a median of 78 days from onset of symptoms. Overall, cardiovascular events, infections and gastrointestinal bleeding were the main major adverse events. Post-COVID-19 cachexia was observed in 25/189 (13%) patients. Lower initial albuminaemia was significantly associated with this cachexia. No reinfection with severe acute respiratory syndrome coronavirus 2 was observed., Conclusions: This work demonstrates the long-term consequences of COVID-19 in MHD patients, highlighting both initial and long-term severity of the disease, including severe cachexia., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)