Tag: nevin manimala

Clin Rheumatol. 2022 Jan 15. doi: 10.1007/s10067-022-06051-z. Online ahead of print.

ABSTRACT

OBJECTIVE: The apoptotic signaling pathway is obviously disordered in systemic lupus erythematosus (SLE). Natural IgM (nIgM) is important in clearing apoptotic cells and preventing them from triggering deleterious autoimmunity. B-1 and innate-like B (ILBs) cells are the main nIgM producers. Human CD27⁺IgD⁺ B cells (un-switched memory B cells) are considered ILBs. However, their functional properties in SLE remain undefined.

METHODS: Peripheral blood sample of 50 SLE patients and 50 healthy controls were collected, and twelve SLE patients were assessed in a follow-up study. The amount of CD27⁺IgD⁺ B cell in each population was analyzed by flow cytometry. The IgM and IL-10 levels of CD27⁺IgD⁺ B cell were assessed by ELISPOT and qRT-PCR, respectively. SPSS 17.0 (SPSS, USA) was employed for data analysis. P < 0.05 indicated statistical significance.

RESULT: The amounts of CD27⁺IgD⁺ B cell were significantly decreased in SLE patients than healthy control (P < 0.01). CD27⁺IgD⁺ B cell amounts were positively correlated with WBC (r = 0.337, P = 0.017), platelet count (r = 0.396, P = 0.004), and serum C3 levels (r = 0.415, P = 0.003) and negatively correlated with serum creatinine levels (r = – 0.285, P = 0.045), SLEDAI(r = – 0.724, P = 0.000), and anti-dsDNA(r = – 0.477, P = 0.000). The IgM and IL-10 levels of CD27⁺IgD⁺ B in active SLE were decreased than healthy control (P < 0.001). Moreover, CD27⁺IgD⁺ B cells are increased in SLE cases after treatment than before treatment (P < 0.001).

CONCLUSION: The amounts of CD27⁺IgD⁺ B cell were significantly decreased in SLE patients compared with the healthy population, and CD27⁺IgD⁺ B cell was verified to be correlated with clinical and immunological features in SLE patients. CD27⁺IgD⁺ B cells had impaired function associated with IgM and IL-10 production in active SLE. Moreover, the amounts of CD27⁺IgD⁺ B cells were recovered to the normal level in SLE cases with treatment-related disease remission. Key Points • CD27⁺IgD⁺ B cell amounts are significantly decreased in SLE patients than healthy control. • CD27⁺IgD⁺ B cells are functionally impaired in producing natural antibody-like IgM and IL-10 in SLE patients. • CD27⁺IgD⁺ B cell amounts are correlated with clinical and immunological features in SLE.

PMID:35032222 | DOI:10.1007/s10067-022-06051-z

J Mater Sci Mater Med. 2022 Jan 15;33(1):11. doi: 10.1007/s10856-021-06639-y.

ABSTRACT

Pyrophosphate-containing calcium phosphate implants promote osteoinduction and bone regeneration. The role of pyrophosphate for inflammatory cell-mesenchymal stem cell (MSC) cross-talk during osteogenesis is not known. In the present work, the effects of lipopolysaccharide (LPS) and pyrophosphate (PPi) on primary human monocytes and on osteogenic gene expression in human adipose-derived MSCs were evaluated in vitro, using conditioned media transfer as well as direct effect systems. Direct exposure to pyrophosphate increased nonadherent monocyte survival (by 120% without LPS and 235% with LPS) and MSC viability (LDH) (by 16-19% with and without LPS). Conditioned media from LPS-primed monocytes significantly upregulated osteogenic genes (ALP and RUNX2) and downregulated adipogenic (PPAR-γ) and chondrogenic (SOX9) genes in recipient MSCs. Moreover, the inclusion of PPi (250 μM) resulted in a 1.2- to 2-fold significant downregulation of SOX9 in the recipient MSCs, irrespective of LPS stimulation or culture media type. These results indicate that conditioned media from LPS-stimulated inflammatory monocytes potentiates the early MSCs commitment towards the osteogenic lineage and that direct pyrophosphate exposure to MSCs can promote their viability and reduce their chondrogenic gene expression. These results are the first to show that pyrophosphate can act as a survival factor for both human MSCs and primary monocytes and can influence the early MSC gene expression. Graphical abstract.

PMID:35032239 | DOI:10.1007/s10856-021-06639-y

Parasitol Res. 2022 Jan 15. doi: 10.1007/s00436-022-07432-8. Online ahead of print.

ABSTRACT

The northern fowl mite (NFM), Ornithonyssus sylviarum, and the poultry red mite (PRM), Dermanyssus gallinae, are the most serious pests of poultry, both of which have an expanding global prevalence. Research on NFM has been constrained by a lack of genomic and transcriptomic data. Here, we report and analyze the first global transcriptome data across all mite live stages and sexes. A total of 28,999 unigenes were assembled, of which 19,750 (68.10%) were annotated using seven functional databases. The biological function of these unigenes was classified using the GO, KOG, and KEGG databases. To gain insight into the chemosensory receptor-based system of parasitiform mites, we furthermore assessed the gene repertoire of gustatory receptors (GRs) and ionotropic receptors (IRs), both of which encode putative ligand-gated ion channel proteins. While these receptors are well characterized in insect model species, our understanding of chemosensory detection in mites and ticks is in its infancy. To address this paucity of data, we identified 9 IR/iGluRs and 2 GRs genes by analyzing transcriptome data in the NFM, while 9 GRs and 41 IR/iGluRs genes were annotated in the PRM genome. Taken together, the transcriptomic and genomic annotation of these two species provide a valuable reference for studies of parasitiform mites and also help to understand how chemosensory gene family expansion/contraction events may have been reshaped by an obligate parasitic lifestyle compared with their free-living closest relatives. Future studies should include additional species to validate this observation and functional characterization of the identified proteins as a step forward in identifying tools for controlling these poultry pests.

PMID:35032220 | DOI:10.1007/s00436-022-07432-8

Eur Arch Otorhinolaryngol. 2022 Jan 15. doi: 10.1007/s00405-021-07245-y. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study is to evaluate speech perception outcomes after a frequency reallocation performed through the creation of an anatomically based map obtained with Otoplan^®, a tablet-based software that allows the cochlear duct length to be calculated starting from CT images.

METHODS: Ten postlingually deafened patients who underwent cochlear implantation with MED-EL company devices from 2015 to 2019 in the Tertiary referral center University Hospital of Verona have been included in a retrospective study. The postoperative CT scans were evaluated with Otoplan^®; the position of the intracochlear electrodes was obtained, an anatomical mapping was carried out and then it was submitted to the patients. All patients underwent pure tonal and speech audiometry before and after the reallocation and the audiological results were processed considering the Speech Recognition Threshold (SRT), the Speech Awareness Threshold (SAT) and the Pure Tone Average (PTA). The differences in the PTA, SAT and SRT values before and after the reallocation were determined. The results were statistically processed using the software Stata with a significance value of α < 0.05.

RESULTS: The mean values of SRT (61.25 dB versus 51.25 dB) and SAT (49 dB versus 41 dB) were significantly lower (p: 0.02 and p: 0.04, respectively) after the reallocation. No significant difference was found between PTA values (41.5 dB versus 39.25 dB; p: 0.18).

CONCLUSIONS: Our preliminary results demonstrate better speech discrimination and rapid adaptation in implanted postlingually deaf patients after anatomic mapping and subsequent frequency reallocation.

PMID:35032205 | DOI:10.1007/s00405-021-07245-y

Eur Child Adolesc Psychiatry. 2022 Jan 15. doi: 10.1007/s00787-022-01941-8. Online ahead of print.

NO ABSTRACT

PMID:35032215 | DOI:10.1007/s00787-022-01941-8

Arch Dermatol Res. 2022 Jan 15. doi: 10.1007/s00403-021-02317-9. Online ahead of print.

ABSTRACT

The timing pattern in which dipeptidyl-peptidase IV inhibitors (DPP4i) confer the risk of bullous pemphigoid (BP) is unknown. To investigate the odds of BP following exposure to DPP4i and to perform a duration-response analysis evaluating the risk of BP in relation to the duration of exposure to the culprit drug. A population-based nested case-control study was performed comparing diabetic patients with BP (n = 1458) with age-, sex- and ethnicity-matched diabetic control subjects (n = 6051) with respect to the prevalence of exposure to DPP4i. Adjusted odds ratios (ORs) were estimated by logistic regression. Overall exposure to DPP4i was associated with an 80% increase in the odds of subsequent BP (OR, 1.81; 95% CI, 1.46-2.08; P < 0.001). In an intraclass analysis, the odds of BP were increased in association with vildagliptin (OR, 3.40; 95% CI, 2.69-4.29; P < 0.001) and sitagliptin (OR, 1.56; 95% CI, 1.33-1.84; P < 0.001). In a duration-response analysis, the highest likelihood of BP was found 1-2 years after commencing the drug (OR, 2.66; 95% CI, 1.97-3.59; P < 0.001). The odds of BP were increased across all time periods and retained its statistical significance even ≥ 6 years after the drug initiation (OR, 1.44; 95% CI, 1.09-1.91; P = 0.011). Relative to other diabetic patients with BP, patients with DPP4i-associated BP were more likely to be admitted to inpatient dermatologic wards (OR, 1.66; 95% CI, 1.30-2.13; P < 0.001) and had higher mean(SD) numbers of outpatient dermatologist visits (14.7[14.8] vs. 12.3[13.2], respectively; P = 0.006). DPP4i should be suspected as a predisposing factor for BP even numerous years after the drug initiation.

PMID:35032198 | DOI:10.1007/s00403-021-02317-9

Eur Arch Otorhinolaryngol. 2022 Jan 15. doi: 10.1007/s00405-021-07219-0. Online ahead of print.

ABSTRACT

PURPOSE: Proton pump inhibitors (PPIs) are commonly prescribed for laryngopharyngeal reflux (LPR), but their efficacy remains debated. Alginates is an option for the treatment of LPR with few adverse effects. The study aimed to investigate the non-inferiority of an alginate suspension (Gastrotuss^®) compared to PPIs (Omeprazole) in reducing LPR symptoms and signs.

METHODS: A non-inferiority randomized controlled trial was conducted. Fifty patients with laryngopharyngeal symptoms (Reflux Symptom Index -RSI- ≥ 13) and signs (Reflux Finding Score -RFS- ≥ 7) were randomized in two treatment groups: (A) Gastrotuss^® (20 ml, three daily doses) and, (B) Omeprazole (20 mg, once daily). The RSI and the RFS were assessed at baseline and after 2 months of treatment.

RESULTS: Groups had similar RSI and RFS scores at baseline. From pre- to 2-month posttreatment, the mean RSI significantly decreased (p = 0.001) in alginate and PPI group (p = 0.003). The difference between groups in the RSI change was not significant (95%CI: – 4.2-6.7, p = 0.639). The mean RFS significantly decreased in alginate (p = 0.006) and PPI groups (p = 0.006). The difference between groups in the mean change RFS was not significant (95%CI: – 0.8; 1.4, p = 0.608).

CONCLUSION: After 2 months of treatment, LPR symptoms and signs are significantly reduced irrespective of the treatment. Alginate was non-inferior to PPIs and may represent an alternative treatment to PPIs for the treatment of LPR.

PMID:35032204 | DOI:10.1007/s00405-021-07219-0

Diabetologia. 2022 Jan 15. doi: 10.1007/s00125-021-05640-y. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: We aimed to compare the performance of risk prediction scores for CVD (i.e., coronary heart disease and stroke), and a broader definition of CVD including atrial fibrillation and heart failure (CVD+), in individuals with type 2 diabetes.

METHODS: Scores were identified through a literature review and were included irrespective of the type of predicted cardiovascular outcome or the inclusion of individuals with type 2 diabetes. Performance was assessed in a contemporary, representative sample of 168,871 UK-based individuals with type 2 diabetes (age ≥18 years without pre-existing CVD+). Missing observations were addressed using multiple imputation.

RESULTS: We evaluated 22 scores: 13 derived in the general population and nine in individuals with type 2 diabetes. The Systemic Coronary Risk Evaluation (SCORE) CVD rule derived in the general population performed best for both CVD (C statistic 0.67 [95% CI 0.67, 0.67]) and CVD+ (C statistic 0.69 [95% CI 0.69, 0.70]). The C statistic of the remaining scores ranged from 0.62 to 0.67 for CVD, and from 0.64 to 0.69 for CVD+. Calibration slopes (1 indicates perfect calibration) ranged from 0.38 (95% CI 0.37, 0.39) to 0.74 (95% CI 0.72, 0.76) for CVD, and from 0.41 (95% CI 0.40, 0.42) to 0.88 (95% CI 0.86, 0.90) for CVD+. A simple recalibration process considerably improved the performance of the scores, with calibration slopes now ranging between 0.96 and 1.04 for CVD. Scores with more predictors did not outperform scores with fewer predictors: for CVD+, QRISK3 (19 variables) had a C statistic of 0.68 (95% CI 0.68, 0.69), compared with SCORE CVD (six variables) which had a C statistic of 0.69 (95% CI 0.69, 0.70). Scores specific to individuals with diabetes did not discriminate better than scores derived in the general population: the UK Prospective Diabetes Study (UKPDS) scores performed significantly worse than SCORE CVD (p value <0.001).

CONCLUSIONS/INTERPRETATION: CVD risk prediction scores could not accurately identify individuals with type 2 diabetes who experienced a CVD event in the 10 years of follow-up. All 22 evaluated models had a comparable and modest discriminative ability.

PMID:35032176 | DOI:10.1007/s00125-021-05640-y

J Clin Pharm Ther. 2022 Jan 15. doi: 10.1111/jcpt.13596. Online ahead of print.

ABSTRACT

WHAT IS KNOWN AND OBJECTIVES: Although the apixaban Food and Drug Administration (FDA) package insert recommends dose reduction in patients administered dual strong inhibitors of p-glycoprotein (P-gp) and cytochrome P-450 (CYP) 3A4, there are limited published data regarding potential drug-drug interactions between apixaban (Eliquis) and common p-glycoprotein (P-gp) and CYP3A4 inhibitors co-administered with statins. The aim of this study was to investigate the degree of elevation relative to apixaban serum peak and trough concentration after the co-administration of amiodarone, diltiazem and statins (atorvastatin, rosuvastatin and simvastatin).

METHODS: Patients prescribed apixaban 5mg twice daily for at least one week were identified from the anticoagulation clinic database and contacted for potential enrolment. A total of 117 volunteers were enrolled with eight excluded due to discontinued use, resulting in 109 volunteers (44 females and 65 males delineated into age groups 40-64 and ≥65 years old) completing the observational study. Fifty-five volunteers were administered apixaban without the P-gp inhibitors amiodarone or diltiazem, with or without statins (atorvastatin, rosuvastatin and simvastatin). Fifty-four volunteers were administered apixaban with either amiodarone or diltiazem, with or without statins (atorvastatin, rosuvastatin or simvastatin). Peak and trough concentrations were assessed for each patient utilizing an apixaban anti-Xa assay.

RESULTS: Of the combinations studied, the mean apixaban trough concentration upon co-administration of amiodarone without a statin was elevated compared to apixaban alone (experimental 156.83 +/- 79.59 ng/ml vs. control 104.09 +/- 44.56 ng/ml; p = 0.04). The co-administration of diltiazem and rosuvastatin, and the administration of amiodarone without a statin led to greater than 1.5-fold increase in apixaban concentrations (peak experimental 315.19 +/- 157.53 ng/ml vs control 207.6 +/- 83.38 ng/ml; p = 0.08 and trough experimental 182.03 +/- 95.93 ng/ml vs control 112.32 +/- 37.78 ng/ml; p = 0.17) suggesting the need to assess dose adjustment for patients per the FDA package insert. In addition, the aggregated mean peak (p = 0.0056) and trough (p = 0.0089) elevation of CYP3A4 experimental groups (atorvastatin and simvastatin) co-administered apixaban and diltiazem were statistically significant compared with the aggregated non-CYP3A4 control groups (no statin and rosuvastatin).

WHAT IS NEW AND CONCLUSION: Herein, we report novel data regarding peak and trough apixaban concentrations after concomitant administration of P-gp and CYP3A4 inhibitors (amiodarone or diltiazem) co-administered with statins (atorvastatin, rosuvastatin or simvastatin). Providers should consider utilizing the apixaban anti-Xa assay or comparative heparin anti-Xa assay to determine if patients require dose reduction to decrease adverse events in high-risk patients prescribed apixaban and concomitant p-glycoprotein and CYP3A4 inhibitors amiodarone or diltiazem with and without a CYP3A4 or non-3A4 statin.

PMID:35032137 | DOI:10.1111/jcpt.13596

Soc Psychiatry Psychiatr Epidemiol. 2022 Jan 15. doi: 10.1007/s00127-022-02233-x. Online ahead of print.

ABSTRACT

PURPOSE: To examine the association between mode of delivery (in particular caesarean section) and behavioural outcomes in offspring at six time-points between age 3 and 17 years.

METHODS: Similar to previous work examining the association between mode of delivery and behavioural outcomes in offspring at age 7, we used maternal-reported data from the Millennium Cohort Study. Data on mode of delivery were collected when children were 9 months and categorised as spontaneous vaginal delivery, assisted vaginal delivery, induced vaginal delivery, emergency caesarean section, planned caesarean section and caesarean section after induction of labor. Data on behavioural outcomes were collected at ages 3, 5, 7, 11, 14 and 17 years using the Strengths and Difficulties Questionnaire (SDQ). Crude and adjusted logistic regression examined mode of delivery-behavioural difficulties relationship, using validated SDQ cut-off points (total SDQ ≥ 17, emotional ≥ 5, conduct ≥ 4, hyperactivity ≥ 7, peer problems ≥ 4 and prosocial behaviour ≤ 4). Multilevel models with linear splines examined the association between mode of delivery and repeated measures of SDQ.

RESULTS: There were 18,213 singleton mother-child pairs included at baseline, 13,600 at age 3; 13,831 at age 5; 12,687 at age 7; 11,055 at age 11; 10,745 at age 14 and 8839 at age 17. Adjusted logistic regression suggested few associations between mode of delivery and behavioural outcomes at ages 3, 5, 11, 14 and 17 years using validated SDQ cut-off points. After correction for multiple testing, only the protective association between planned caesarean section-Conduct difficulties at age 5 years (OR 0.63, 95% CI 0.46, 0.85) and positive association between caesarean section after induction-Emotional difficulties at age 11 years (OR 1.57, 95% CI 1.19, 2.07) remained statistically significant. Multilevel modelling suggested mean SDQ scores were similar in each mode of delivery group at each time point.

CONCLUSIONS: Results of this study indicate that mode of delivery is unlikely to have a major impact on behavioural outcomes.

PMID:35032173 | DOI:10.1007/s00127-022-02233-x