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Hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs) are α-ketoglutarate (αKG)-dependent dioxygenases that function as cellular oxygen sensors. However, PHD activity also depends on factors other than oxygen, especially αKG, a key metabolic compound closely linked to amino-acid metabolism. We examined the connection between amino-acid availability and PHD activity. We found that amino-acid starvation leads to αKG depletion and to PHD inactivation but not to HIF stabilization. Furthermore, pharmacologic or genetic inhibition of PHDs induced autophagy and prevented mammalian target of rapamycin complex 1 (mTORC1) activation by amino acids in a HIF-independent manner. Therefore, PHDs sense not only oxygen but also respond to amino acids, constituting a broad intracellular nutrient-sensing network.

The application of cold plasma as an environmentally friendly, efficient, and cost-effective method has garnered interest for its potential to alleviate the deleterious effects of abiotic stress on plants. This study investigates the impact of nitrogen oxide (NO) cold plasma treatment on wheat ( Triticum durum Desf. ‘GAP’) seed germination, seedling growth, and pigment composition under salinity stress conditions. Seeds were exposed to NO cold plasma for 0, 5, 10, and 15 minutes and subsequently sown in Petri dishes with sodium chloride (NaCl) concentrations of 0, 100, 150, and 200 mM to assess morphological and physiological responses between the 7th and 10th days of germination. Results indicated that cold plasma treatment significantly enhanced germination rates and seedling growth under both control and saline conditions, with the 15-min exposure yielding the most pronounced improvements. However, cold plasma treatment alone either decreased leaf pigment content or had no significant effect, whereas under salinity stress, chlorophyll a , chlorophyll b , total chlorophyll, and carotenoid levels showed varied increases with treatment duration. Conversely, anthocyanin levels decreased under salt stress with plasma treatment. The differential effects on pigment composition highlight a complex interaction between cold plasma treatment and plant physiological responses under abiotic stress, suggesting avenues for further research into optimizing treatment protocols for agricultural resilience. This study contributes to the growing body of knowledge on cold plasma applications in agriculture, offering insights into sustainable practices that could mitigate the impacts of global challenges like soil salinity on crop production.

Crude oil is a common environmental pollutant composed of a large number of both aromatic and aliphatic hydrocarbons. Biodegradation is carried out by microbial communities that are important in determining the fate of pollutants in the environment. The intrinsic biodegradability of the hydrocarbons and the distribution in the environment of competent degrading microorganisms are crucial information for the implementation of bioremediation processes. In the present study, the biodegradation capacities of various bacteria toward aliphatic and aromatic hydrocarbons were determined. The purpose of the study was to isolate and characterize hydrocarbon-degrading bacteria from contaminated soil of a refinery in Arzew, Algeria. A collection of 150 bacterial strains was obtained; the bacterial isolates were identified by 16S rRNA gene sequencing and their ability to degrade hydrocarbon compounds characterized. The isolated strains were mainly affiliated to the Gamma-Proteobacteria class. Among them, Pseudomonas spp. had the ability to metabolize high molecular weight hydrocarbon compounds such as pristane (C19) at 35.11 % by strain LGM22 and benzo[a] pyrene (C20) at 33.93 % by strain LGM11. Some strains were able to grow on all the hydrocarbons tested including octadecane, squalene, phenanthrene, and pyrene. Some strains were specialized degrading only few substrates. In contrast, the strain LGM2 designated as Pseudomonas sp. was found able to degrade both linear and branched alkanes as well as low and high poly-aromatic hydrocarbons (PAHs). The alkB gene involved in alkane degradation was detected in LGM2 and other Pseudomonas -related isolates. The capabilities of the isolated bacterial strains to degrade alkanes and PAHs should be of great practical significance in bioremediation of oil-contaminated environments.

IntroductionSystematic reviews have shown that powered toothbrushes (PTs) are more effective than manual toothbrushes (MTs), but with only minor effect sizes. Whether PTs are used adequately, however, has not been investigated so far. The aim of the present study was therefore to analyse motion habits with PT in comparison to MT toothbrushes by video observation.Materials and methodsOne hundred subjects were enrolled in this observational trial and brushed their teeth in randomised order with a MT and PT while being video-filmed, resulting in 95 analysable sets of recordings. Parameters of interest were brushing duration (s; median (min;max)), type of brushing strokes, area of brushing, changes between areas (n; median (min;max)) and brushing sequence.ResultsBrushing duration was 145 s (60;354) and 135 s (48;271) for PT and MT, respectively (p ≤ 0.001). Subjects brushed vestibular surfaces completely, but reached oral surfaces to a much lesser extent, regardless of the toothbrush type. With both toothbrushes, subjects moved frequently between areas (MT 35 (14;79); PT 33 (14;85); n.s.) and brushed predominantly with circling and horizontal strokes; with the PT, 50.5% of the subjects spent only <10% of the brushing duration with passive brushing (positioning the brush head on the teeth with ≤2 movements/s).ConclusionsIntra-individual motion patterns were similar with both MT and PT, and most subjects persisted in their habitual motion patterns regardless of the toothbrush type.Clinical relevanceThe use of PT and MT may need intensive training and supervision from oral hygiene educators in order to help subjects taking full advantage from these devices.

We construct a climatology of Lagrangian coherent structures (LCSs)—the concealed skeleton that shapes transport—with a twelve-year-long data-assimilative simulation of the sea-surface circulation in the Gulf of Mexico (GoM). Computed as time-mean Cauchy–Green strain tensorlines of the climatological velocity, the climatological LCSs (cLCSs) unveil recurrent Lagrangian circulation patterns. The cLCSs strongly constrain the ensemble-mean Lagrangian circulation of the instantaneous model velocity, showing that a climatological velocity can preserve meaningful transport information. The quasi-steady transport patterns revealed by the cLCSs agree well with aspects of the GoM circulation described in several previous observational and numerical studies. For example, the cLCSs identify regions of persistent isolation, and suggest that coastal regions previously identified as high-risk for pollution impact are regions of maximal attraction. We also show that cLCSs are remarkably accurate at identifying transport patterns observed during the Deepwater Horizon and Ixtoc oil spills, and during the Grand LAgrangian Deployment (GLAD) experiment. Thus it is shown that computing cLCSs is an efficient and meaningful way of synthesizing vast amounts of Lagrangian information. The cLCS method confirms previous GoM studies, and contributes to our understanding by revealing the persistent nature of the dynamics and kinematics treated therein.

The Brazil Current (BC) is a weak western boundary current flowing along the Southwestern Atlantic Ocean. It is frequently described as a flow with intense mesoscale activity and relatively low volume transport between 5.0 and 10.0 Sv. We use a 13-year eddy-resolving primitive-equation simulation to show that the presence of persistent meanders and eddies leads to characteristic quasi-steady Lagrangian transport patterns, aptly extracted through climatological Lagrangian Coherent Structures (cLCS). The cLCS position the surface expression of the BC core along the 2000-m isobath, in excellent visual agreement with high resolution satellite sea-surface temperature and the model Eulerian mean velocity. The cLCS deformation pattern also responds to zonally persistent cross-shelf SSH transition from positive (high) values near coastline to low (negative) values between 200- and 2000-m and back to positive (high) offshore from the 2000-m isobath. Zonally-paired cyclonic and anticyclonic structures are embedded in this transition, also causing the cLCS to deform into chevrons. An efficient transport barrier is identified close to the 200-m isobath confirmed by limited inshore movement of drogued drifters and accurately indicated by an along slope maxima of climatological strength of attraction. We also show that the persistent cyclonic and anticyclonic structures may induce localized cross-shelf transport. Regions of low climatological strength of attraction coincide with large shelves and with stagnant synthetic trajectories. We also show that cLCS accurately depict trajectories initiated at the location of Chevron’s spill (November 2011) as compared to synthetic and satellite-tracked trajectories, and the outline of the oil from that accident. There is also an agreement between the large-scale oil slicks reaching the Brazilian beaches (from August 2019 to February 2020) and the strength of climatological attraction at the coast. Our work also clarifies the influence of persistent mesoscale structures on the regional circulation. The identification and quantitative description of climatological Lagrangian coherent structures is expected to improve the effectiveness of future emergency response to oil spills, contingency planning, rescue operations, larval and fish connectivity assessment, drifter launch strategies, waste pollutant and marine debris dispersion and destination.

Background Polypharmacy increases the risk of pharmacological interactions, prevalence of secondary effects and with this the lack of adherence to treatment. It is estimated that between 10 and 40% of patients hospitalized in psychiatric institutions are prescribed more than one antipsychotic. The objective of the present study was to identify the prevalence of polypharmacy, evaluate adverse effects associated to the use of psych drugs and to estimate the risk in specific groups. Methods We carried out a longitudinal, retrospective study that included the analysis of all discharged patients ( n  = 140) in the first trimester of the year in a psychiatric hospital in Mexico. The information was classified into 7 sections: sociodemographic, diagnosis, clinical follow-up information, prescribed drugs, adverse reactions, substance abuse, laboratory and complementary results. Risk estimation was obtained with Odds Ratios, to correlate continuous variables Pearson’s correlation was used. Student’s T and Mann Whitney’s U were used to compare 2 independent samples; multiple and linear regressions were carried out. Results The mean number of drugs used during hospitalization was 7.8 drugs per patient. The mean prescribed psych drugs was 4.07. The mean antipsychotic dose was the risperidone equivalent of 5.08 mg. 29.2% of patients had at least one secondary effect associated to the use of drugs, 17.8% presented extrapyramidal symptoms. 81.4% of patients were prescribed 6 or more drugs (polypharmacy) and were 5 times more likely to suffer a secondary effects (OR 6.24). 14.2% had polypharmacy while receiving antipsychotics and had more than twice the risk of presenting extrapyramidal symptoms (OR 3.05). For each added psych drug, hospital stay increased by 6.56 days. Conclusions Despite international guideline recommendations where reasoned and conciliatory prescription of psych drugs is advised, there is still a high prevalence of polypharmacy in patients hospitalized in psychiatric institutions. In the present study 4 out of 5 patients received polypharmacy decreasing tolerability, treatment adherence and increasing the risk and costs secondary to an increased hospital stay.

Background:Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) constitutes a diverse group of diseases characterized by inflammatory damage to small to medium-sized vessels, leading to organ and tissue impairment. Along with pulmonary and renal, upper airway involvement is a common feature, especially for granulomatosis with polyangiitis. The Sinonasal Outcome Test 22 (SNOT-22) is a 22-item questionnaire that combines both nasal and general health symptoms, providing a quantitative measurement of the severity of various symptoms related to chronic rhinosinusitis, with each question scored on a scale of 0 to 5 and a total possible score of 110. It has been widely used and validated for assessing disease-specific outcomes and quality of life in patients with sinonasal conditions.Objectives:Primary objective of this study was to utilize the SNOT-22 questionnaire to evaluate sinonasal symptoms in AAV patients.Methods:AAV patients followed in Gazi University outpatient rheumatology clinic between January and December 2023 were included in the study. During their routine follow-up, SNOT-22 was administered to all consenting patients. Information regarding demographic, clinical and laboratory was extracted from patient files.Results:A total of 90 AAV patients were included in the study, with a mean age of diagnosis at 47.8 ± 14.4 years. The majority of patients were female (53%) GPA was the predominant diagnosis (75.6). 61 patients (68%) had upper respiratory tract symptoms. ANCA patterns revealed c-ANCA in 55.2% and p-ANCA in 20.7%. Mean BVAS score at the time of diagnosis was 18,3 and median FFS score was 1,0 (Table 1).At the time of SNOT-22 administration, patients had a mean age of 53.7 ± 13.5 years. 35 patients (38.9%) had upper respiratory tract findings, with most common being sensorineural hearing loss in 21.1%. Median CRP was 5,1 mg/L (IQR: 6,9). Most patients were at remission (median BVAS: 0). SNOT-22 median score (IQR) was 0 (4), with 37.8% of patients having a score greater than 0; categorically, 62.2% scored 0, 10% scored 1–3, 14.4% scored 4–9, and 13.3% scored ≥10 (Table 2). There was no difference between SNOT-22 score and demographic, clinical and laboratory findings.Conclusion:SNOT-22 has the potential to be used as a patient reported outcome tool in AAV patients. Further research is needed to confirm this prospectively.REFERENCES: NIL.Table 1.Characteristics of AAV patients at the time of diagnosis.ParameterValueNumber of patientsN=90Gender, n (%) Female48 (53%) Male42 (47%)Age at Diagnosis, mean ± SD47.8 ± 14.4 years (44.8–50.8)Diagnosis, n (%) GPA68 (75.6%) MPA5 (5.6%) EGPA14 (15.6%) Renal-limited AAV3 (3.3%)Clinical, n (%) Constitutional75 (83%) Skin17 (19%) Mucosa and Eyes23 (26%) ENT61 (68%) Pulmonary70 (79%) Cardiovascular15 (17%) Gastrointestinal1 (1%) Renal55 (61%) Nervous Syste26 (29%)Laboratory CRP, median (IQR)97.2 mg/L (187.2) Creatinine, median (IQR)0.97 mg/dL (1.80) Proteinuria, median (IQR)448 mg/g (1376)ANCA IFA, n (%) Not performed4 (4.6%) Negative17 (19.5%) c-ANCA48 (55.2%) p-ANCA18 (20.7%)ANCA ELISA, n (%) Not performed5 (5.8%) Negative19 (22.1%) MPO-ANCA14 (16.3%) PR3-ANCA48 (55.8%)Disease Severit BVAS, mean±SD (95% CI)18.3 ± 7.4 (16.7–19.8) FFS, median (IQR)1.0 (1.0)Table 2.Clinical and laboratory findings at the of SNOT-22 administrationParameterValueAge, mean ± SD (95% CI)53.7 ± 13.5 years (50.85–56.5)Clinical, n (%) Constitutional8 (8.9%) Skin3 (3.3%) Mucosa and Eyes18 (20%) ENT35 (38.9%) Pulmonary39 (44.3%) Cardiovascular21 (23.3%) Gastrointestinal3 (3.3%) Renal53 (58.9%) Nervous System18 (20%)Laboratory ESR, median (IQR)22.5 mm/h (23) CRP, median (IQR)5.1 mg/L (6.9) eGFR (CKD-EPI 2021), median (IQR)86 mL/min/1.73 m2 (49) Proteinuria, median (IQR)163.5 mg/g (321)Disease Assessment BVAS, median (IQR)0 (0) VDI, median (IQR)3.0 (2.0)Relapse, n (%)52 (57.8%)SNOT-22 Score, median (IQR)0 (4)SNOT-22 >0, n (%)34 (37.8%)SNOT-22 Categorical Distribution, n (%) 0 points56 (62.2%) 1–3 points9 (10%) 4–9 points13 (14.4%) ≥10 points12 (13.3%)Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Systemic lupus erythematosus is a significant autoimmune disease characterized by various system involvements. The central nervous system manifestations of systemic lupus erythematosus (NPSLE) exhibit a range of severity and hold an essential prognostic implication. The primary challenge in managing NPSLE is needing a practical diagnostic marker. CXCL13 is a B-cell chemokine which’s role is implicated in SLE in many studies.Objectives:The study aimed to evaluate serum CXCL-13 levels in patients with NPSLE and compare them with SLE patients without neuropsychiatric involvement and healthy controls.Methods:The study group was dichotomized into three subgroups: 1. SLE patients with NPSLE (n=32), 2. SLE patients without NPSLE (n=71) 3. Healthy controls (n=22). Patients with NPSLE were divided into two subgroups: those with active neurological involvement (n=6) and those with previous neurological involvement currently in remission (n=26). Disease activity was calculated according to the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI version of SLEDAI score (PMID: 1599520). Serum CXCL-13 levels were detected with human enzyme-linked immunosorbent assay (ELISA, double antibody sandwich method) kits according to the manufacturer’s instructions (BT Human BLC (CXCL13) ELISA Kit, USA). SPSS 17.0 version (Chicago, USA) was used for the statistical data analysis.Results:A total of 125 participants were enrolled in the study with a mean age of 42.8 years (123 female (96.03 %)/5 male (3.97 %)). All clinical involvements and laboratory parameters associated with SLE diagnosis and activity between patient groups were compared in Table 1. When patients were grouped according to the existence of NPSLE without regarding activity, patients with NPSLE had higher serum CXCL-13 levels when compared to SLE patients without NPSLE (median (IQR); 263.2 (132.8) ng/mL vs 204.2 (123.7) ng/mL, p= 0.047) and healthy controls (median (IQR); 263.2 (132.8) ng/mL vs 143.0 (70.2) ng/mL, p<0.001, Figure 1). Also, patients who didn’t have a history of NPSLE had significantly higher levels of serum CXCL-13 compared to controls (p<0.001). Also, patients with NPSLE had significantly higher levels of antidsDNA antibody (p=0.031) and lower levels of total C3 (p= 0.047) than those without NPSLE. Total C4 levels were similar between these groups (p=0.162).Conclusion:NPSLE represents a challenging clinical manifestation characterized by difficulties in both diagnosis and management. The necessity of prompt intervention poses clinicians in a problematic situation. The need for a specific diagnostic biomarker stems from this challenge. In this regard, serum levels of CXCL-13 appear promising in filling this diagnostic gap.Table 1.Figure 1.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:In patients diagnosed with Sjögren’s syndrome (SjS), there is an increased risk of hematologic malignancies, and predictive factors are well-known. Familial clustering and HLA haplotype association suggest that genetic factors disrupting the regulation of the immune system may predispose individuals to both neoplasms and autoimmune diseases, potentially leading to an increased frequency of cancer development in close relatives of SjS patients.Objectives:In this study, our aim was to assess the frequency of cancer development in close relatives of individuals diagnosed with SjS.Methods:Consecutive patients who were actively followed up in the rheumatology outpatient clinic at Gazi University Hospital and who met the 2016 ACR-EULAR classification criteria for SjS were included in the study. Direct interviews were conducted with the patients, and communication was established through telephone numbers registered in the hospital system. The risk of developing acancer in SjS patients and their first-degree relatives was calculated by comparing it with the general population of Turkey. Cancer incidence data for the general population of Turkey were obtained from the Global Cancer Observatory of the World Health Organization International Agency for Research on Cancer (GLOBOCAN).Results:323 SjS patients (F/M: 313/10, mean age: 56±11), 9% (n=29) had a history of malignancy, with 5.9% (n=19) having solid organ malignancy and 3.1% (n=10) hematologic malignancy. Breast cancer was the most common at 2.2%, and other cancers (bladder, rectum, cervix, endometrium, colon) were observed in 1.5%. The median follow-up was 3.58 years, and the standardized incidence ratio (SIR) for all cancers was 3.3 (95% CI: 2.2–4.7, P<0.001). Leukemia or lymphoma cases had an SIR of 22.5 (95% CI: 10.8–41.4, P<0.001). Among 313 women, seven cases of breast cancer had an SIR of 3.8 (95% CI: 1.5–7.9, P<0.001). Malignancy development in SjS patients did not differ based on age, gender, SjS type, smoking history, Schirmer, anti-SSA, anti-SSB, ANA, ESSDAI positivity-negativity, complement levels, and Focus score.43.3% of SjS patients (n=128) had a family history of cancer (parents, siblings, children), totaling 176 cases (Table 1). Among 1750 relatives, the SIR was 3.5 (95% CI: 3.0-4.1, P<0.001). Notably, specific cancers showed varying SIRs: lung (2.66), breast (4.6), colon (3.7), stomach (4.3), prostate (2.8), brain tumor (4.6), laryngeal (7.8), endometrium (5.5), ALL (4.9), liver (4.1), and kidney tumor (4.6) (Table 2). The average age of relatives with cancer was 58±10 years; 56% were male, and 7.4% were active smokers. No significant differences were found in SjS type, Schirmer result, focus score, SSA, SSB, ANA, RF, complement levels, IgA, IgM, IgG levels, and ESSDAI status when comparing SjS patients with and without relatives with cancer.Conclusion:In our study, we found that close relatives of SjS patients have an increased risk of developing cancer compared to the general population. No study was found in the literature that investigated the incidence of cancer in close relatives of SjS patients. There is a need for larger population-based studies on this topic to clarify this association.REFERENCES:NIL.Table 1.Cancer Types Observed in Close Relatives of Patients Diagnosed with Sjögren’s SyndromeCancer TypeN (%)Lung41 (23.3)Breast25 (14.2)Colon20 (11.4)Stomach16 (9.0)Prostate12 (6.8)Leukemia11 (6.2)Brain8 (4.5)Endometrium7 (4.0)Larynx7 (4.0)Liver5 (2.8)Kidney5 (2.8)Thyroid4 (2.3)Pancreas4 (2.3)Ewing’s Sarcoma2 (1.1)Other*9 (5.1)Total176 (100.0)Table 2.Standardized Incidence Ratios of Cancer Types in Close Relatives of Patients Diagnosed with Sjögren’s SyndromeCancer TypeSIR95% CIPAll3.53.0 - 4.1<0.001Lung2.661.9 - 3.6<0.001Breast4.62.95 - 6.86<0.001Colon3.72.3 - 5.7<0.001Stomach4.32.5 - 7.1<0.001Prostate2.81.4 - 4.8<0.01Brain4.61.7 - 10<0.01Larynx7.83.1 - 16<0.001Endometrium5.52.2 - 11.3<0.001ALL4.91.8 - 10.7<0.01Liver4.11.3 - 9.6<0.05Renal4.61.5 - 10.8<0.05Acknowledgements:NIL.Disclosure of Interests:None declared.