Assessing safety and efficacy of TNFi treatment in late onset ankylosing spondylitis: a TURKBIO registry study.

Clinical data on the use of tumour necrosis factor inhibitors (TNFi) in late-onset ankylosing spondylitis (LoAS) are limited. The present study aimed to evaluate efficacy, safety, and treatment adherence associated with the initial use of TNFi therapy in biologic naive patients diagnosed with LoAS. Patients whose age of onset was ≥ 45 years and < 45 years were classified as having LoAS and YoAS, respectively, based on the age of symptom onset. There were 2573 patients with YoAS and 281 LoAS. Baseline disease activity measures were similar between the groups. No significant differences were seen between the two groups in response to treatment and in remaining on the first TNFi at 6, 12 and 24 months. In the LoAS group, the analysis showed that TNFi discontinuation was linked to VAS pain score (HR 1.04; 95% CI 1.01-1.06). Patient groups had similar rates of adverse events (YoAS: 8.7% vs. LoAS: 11.7%). In both biologic naive LoAS and YoAS patients, the study showed that the initial TNFi therapy was equally effective and safe.

Biological treatment in elderly and young patients with ankylosing spondylitis: TURKBIO real-life data results.

Objectives: This study aims to investigate the effect of age on disease activity and biological treatment in patients with ankylosing spondylitis (AS). Patients and methods: A total of 811 AS patients registered in the TURKBIO registry database between 2011 and 2019 were categorized according to their age at the time of entry into the registry and assigned to one of two groups: young patients, defined as <60 years of age (n=610), and those aged ≥60 years (n=201) were recorded as elderly patients. Demographic, clinical, and laboratory characteristics, along with disease activity markers and other follow-up parameters, as well as current and prior treatments, were electronically recorded during each visit using open-source software. Results: The mean age of the elderly patients was 67±5.8 years, while the mean age of the younger patients was 49.2±10.9 years. Male predominance was lower in the older AS group compared to the younger AS group (p=0.002). During follow-up period, 397 patients (comprising 318 young and 79 elderly individuals) had a history of using at least one biological disease-modifying agent (bDMARD). There was no significant difference between the groups in terms of DMARD and bDMARD-use distributions. First tumor necrosis factor inhibitor (TNFi) retention rates were found to be similar in both groups over 10 years of follow-up. Adverse events were found to be similar in young (19.9%) and elderly (26.8%) AS patients. Conclusion: Research in the TURKBIO cohort reveals that both older and younger patients with AS exhibited similar disease activity levels with comparable treatment approaches. Moreover, the results of TNFi treatments in elderly patients were the same as those observed in younger patients, with no notable increase in safety concerns.

Influence of point mutations on PR65 conformational adaptability: Insights from molecular simulations and nanoaperture optical tweezers.

PR65 is the HEAT repeat scaffold subunit of the heterotrimeric protein phosphatase 2A (PP2A) and an archetypal tandem repeat protein. Its conformational mechanics plays a crucial role in PP2A function by opening/closing substrate binding/catalysis interface. Using in silico saturation mutagenesis, we identified PR65 "hinge" residues whose substitutions could alter its conformational adaptability and thereby PP2A function, and selected six mutations that were verified to be expressed and soluble. Molecular simulations and nanoaperture optical tweezers revealed consistent results on the specific effects of the mutations on the structure and dynamics of PR65. Two mutants observed in simulations to stabilize extended/open conformations exhibited higher corner frequencies and lower translational scattering in experiments, indicating a shift toward extended conformations, whereas another displayed the opposite features, confirmed by both simulations and experiments. The study highlights the power of single-molecule nanoaperture-based tweezers integrated with in silico approaches for exploring the effect of mutations on protein structure and dynamics.

The role of fatty acids in patients with Behçet's disease and their association with thrombosis.

Behçet's disease (BD) is a systemic disease with unknown etiopathogenesis and varying disease presentations. Fatty acids (FA) are essential biological compounds that are involved in complex metabolic pathways. They may contribute to inflammation and endothelial dysfunction by participating in many signaling pathways. Increased FAs levels are associated with an increased risk for various diseases. This study aimed to determine the relationship between FA, BD, and thrombotic complications. A total of 97 patients were recruited from the rheumatology department of a single center as a case-control study. The participants were divided into three groups: 36 patients with BD with thrombosis (Group 1), 24 patients with BD without thrombosis (Group 2), and 37 age- and sex-matched controls (Group 3). The analysis of 37 different FA with carbon numbers in the range of (4:0) and (24:1) in the samples were analyzed and compared between groups. Myristic acid (MA), methyl eicosatrienoate, and stearic acid (STA) levels were found to be significantly higher in BD with thrombosis than in BD without thrombosis, and palmitic acid (PA) levels were significantly higher in BD with thrombosis than in healthy individuals. MA was found to be a significant marker for differentiating between thrombotic BD. PA and STA are important markers for detecting thrombotic BD. In BD, lipotoxicity created by FA, such as PA, STA, and MA, plays a role as an inducer of inflammation and thrombosis through various mechanisms.

Antibacterial wound dressing with cross-linked electrospun surface from reduced graphene oxide doped polyvinyl alcohol/sodium caseinate blends.

In this study, a new biomaterial with polyvinyl alcohol (PVA)/sodium caseinate (SodCa)/reduced graphene oxide (rGO) structure was developed. Antibacterial effective nanofibers were successfully produced by electrospinning method from 1%, 3%, 5%, and 7% rGO added PVA/SodCa (60:40, w:w) solution mixtures prepared for use as modern wound dressings. To create a usage area, especially in exuding wounds, hydrophilic PVA/SodCa/rGO electrospun mats were cross-linked by dipping them in a glutaraldehyde (GLA) bath. The surface micrographs of all nanofibers were homogeneous and smooth. rGO-doped biomaterials were obtained as thin nanofibers in the range of 301-348 nm. Nanofibers, which were completely soluble in water, after cross-linking preserved their existence in the range of 87%-81% at the end of the 24th hour in distilled water. It was reported that these biomaterials that persist in an aqueous environment show swelling behavior in the range of 275%-608%. The porosity of uncross-linked pure PVA/SodCa nanofibers increased by 46.75% after cross-linking. Moreover, the tensile strength of cross-linked PVA/SodCa electrospun mats increased in the presence of rGO. Provided that wound dressing is done every 24 h with 3% rGO-doped PVA/SodCa nanofiber and provided that wound dressing is done every 48 h with 5% rGO-doped PVA/SodCa nanofiber showed antibacterial activity against S. aureus as 99.38% and 99.55%, respectively.

Determining the Effect of Telehealth Intervention for Lupus Patients on Pain, Happiness, and Life Activities: A Randomized Controlled Study.

PURPOSE: This study aims to determine the effect of a telehealth intervention for SLE patients on pain, happiness, and life activities. METHODS: The study was conducted as a randomized controlled study. The sample of the study consisted of a total of 73 participants, including the experimental group (n = 37) and the control group (n = 36). Random number generation using Excel was used to determine how subjects were randomly assigned to treatment and control groups. Numerical Rating Scale, Oxford Happiness Scale Short Form, and Life Activities Scale were used to collect data. In addition to their routine treatments, participants in the experimental group received telehealth intervention once a week for 12 weeks, each intervention lasting 15 to 20 minutes. No application was made to the control group during the intervention. Scales were applied to both groups at the beginning of the study, in the 6th week, and in the 12th week. RESULTS: Pain scores of the experimental group were lower at the 6th and 12th weeks compared to the beginning. While there was no difference in pain comparison between the groups at the 6th and 12th weeks, the pain score of the experimental group at the 12th week was significantly lower than the control group. It was determined that the happiness scale scores in the experimental group were higher at the 6th and 12th weeks compared to the beginning. At the end of the 12th week, the happiness score of the experimental group was higher than the control group. It was determined that the life activities scores in the experimental group were higher at the 6th and 12th weeks compared to the beginning. CONCLUSION: It has been determined that telehealth application has a positive effect on the pain, happiness, and life activities of SLE participants. We suggest that future research should be conducted to improve the body image of SLE participants.

The mechanism and energetics of the dynein priming stroke.

Dyneins are an AAA+ motor responsible for motility and force generation toward the minus end of microtubules. Dynein motility is powered by nucleotide-dependent transitions of its linker domain, which transitions between straight (post-powerstroke) and bent (pre-powerstroke) conformations. To understand the dynamics and energetics of the linker, we performed all-atom molecular dynamics simulations of human dynein-2 primed for its power stroke. Simulations revealed that the linker can adopt either a bent conformation or a semi-bent conformation, separated by a 5.7 kT energy barrier. The linker cannot switch back to its straight conformation in the pre-powerstroke state due to a steric clash with the AAA+ ring. Simulations also showed that an isolated linker has a free energy minimum near the semi-bent conformation in the absence of the AAA+ ring, indicating that the linker stores energy as it bends and releases this energy during the powerstroke.

Spousal support and dyadic adjustment in the early postpartum period.

In the study, we aimed to investigate the effects of perceived spousal support and dyadic adjustment on the psychological well-being of women in the early postpartum period. This descriptive and correlational study consisted of 367 women giving birth in the postpartum department between 15th July and 31st October 2022. The data were collected using the Personal Information Form, the Perceived Spousal Support Among Women in Early Postpartum Period (PSSAWEPP), the Revised Dyadic Adjustment Scale (RDAS), and the Psychological Well-Being Scale (PWBS). The average scores of PSSAWEPP, RDAS, and PWBS in the mothers were found as 61.79 ± 7.73, 54.16 ± 6.28, and 45.87 ± 5.74, respectively. The elevated scores of perceived spousal support (ß = 0.234, p < .001) and dyadic adjustment (ß = 0.270, p < .001) of women led to a significant increase in the level of psychological well-being. In conclusion, the support received by women from spouses and dyadic adjustment affect the psychological well-being of women in the early postpartum period.

Does obesity affect treatment response to secukinumab and survival in ankylosing spondylitis? Real-life data from the TURKBIO Registry.

OBJECTIVES: The aim of this study was to evaluate the impact of obesity on the treatment response to secukinumab and drug survival rate in patients with ankylosing spondylitis (AS). METHODS: We performed an observational cohort study that included AS patients based on the biological drug database in Turkey (TURKBIO) Registry between 2018 and 2021. The patients were divided into three groups: normal [body mass index (BMI) < 25 kg/m2], overweight (BMI: 25-30 kg/m2), and obese (BMI ≥ 30 kg/m2). Disease activity was evaluated at baseline, 3, 6, and 12 months. Drug retention rates at 12 months were also investigated. RESULTS: There were 166 AS patients using secukinumab (56.6% male, mean age: 44.9 ± 11.6 years). The median follow-up time was 17.2 (3-33.2) months. Forty-eight (28.9%) patients were obese. The mean age was higher in the obese group than in others (P = .003). There was no statistically significant difference in Bath Ankylosing Spondylitis Disease Activity Index 50, Assessment of SpondyloArthritis international Society 20 (ASAS20), ASAS40, Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity, and ASDAS clinically important improvement responses between the three groups at 3, 6, and 12 months, although they were numerically lower in obese patients. Drug retention rates at 12 months were similar in all groups (P > .05). CONCLUSIONS: This study suggested that obesity did not affect secukinumab treatment response and drug retention in AS patients.

Altered kynurenine pathway metabolism and association with disease activity in patients with systemic lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by increased release of proinflammatory cytokines that are known to activate the indoleamine 2,3-dioxygenase (IDO-1) enzyme, which catalyzes the rate-limiting step of the kynurenine pathway (KP). This study aimed to measure KP metabolite levels in patients with SLE and investigate the relationship between disease activity, clinical findings, and KP. The study included 100 patients with SLE and 100 healthy controls. Serum tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), quinolinic acid (QA) concentrations were measured with tandem mass spectrometry. Serum KYN, KYNA, 3HAA, 3HK, and QA levels of the patients with SLE were significantly higher than the control group. Serum QA levels were elevated in patients with neurological involvement (four patients with peripheral neuropathy and two patients with mononeuropathy), serum KYN levels and KYN/TRP ratio increased in patients with joint involvement, and serum KYN, 3HK, and 3HAA levels and the KYN/TRP ratio were increased in patients with renal involvement. Moreover, KYN and KYN/TRP ratios were positively correlated with the disease activity score. These findings indicated that imbalances in KP metabolites may be associated with the pathogenesis, activation, and clinical manifestations of SLE.

Influence of Point Mutations on PR65 Conformational Adaptability: Insights from Nanoaperture Optical Tweezer Experiments and Molecular Simulations.

PR65 is the HEAT-repeat scaffold subunit of the heterotrimeric protein phosphatase 2A (PP2A) and an archetypal tandem-repeat protein, forming a spring-like architecture. PR65 conformational mechanics play a crucial role in PP2A function by opening/closing the substrate-binding/catalysis interface. Using in-silico saturation mutagenesis we identified "hinge" residues of PR65, whose substitutions are predicted to restrict its conformational adaptability and thereby disrupt PP2A function. Molecular simulations revealed that a subset of hinge mutations stabilized the extended/open conformation, whereas another had the opposite effect. By trapping in nanoaperture optical tweezer, we characterized PR65 motion and showed that the former mutants exhibited higher corner frequencies and lower translational scattering, indicating a shift towards extended conformations, whereas the latter showed the opposite behavior. Thus, experiments confirm the conformations predicted computationally. The study highlights the utility of nanoaperture-based tweezers for exploring structure and dynamics, and the power of integrating this single-molecule method with in silico approaches.

Unintentional Monotherapy in Rheumatoid Arthritis Patients Receiving Tofacitinib and Drug Survival Rate of Tofacitinib.

OBJECTIVE: To determine the rate of unintentional monotherapy (UM; switching to monotherapy from combination therapy of patients' own volition) in rheumatoid arthritis patients receiving tofacitinib and to evaluate tofacitinib survival rate. METHODS: This national, multicenter study included patients' data from the TURKBIO Registry. Demographics, clinical characteristics, disease duration and activity, comorbidities, and treatments were analyzed. RESULTS: Data of 231 rheumatoid arthritis patients (84.8% female, median age, 56 years) were included; 153 were initially prescribed combination therapy and continued to their therapies; 31 were initially prescribed combination therapy but switched to monotherapy on their own volition (UM); 21 were initially prescribed monotherapy and switched to combination therapy; 26 were initially prescribed monotherapy and continued to their therapies. The rate of comorbidities at the time of data retrieval was higher in the UM group than in the combination group (83.3% vs. 60.3%, p = 0.031). Presence of comorbidities was a significant factor affecting switching to monotherapy ( p = 0.039; odds ratio, 3.29; 95% confidence interval, 1.06-10.18). The combination and UM groups did not differ regarding remission rate assessed by Disease Activity Score 28-joint count C-reactive protein (60.5% and 70%, respectively; p = 0.328). Drug survival rates of the UM and combination groups did not differ. The median drug survival duration of tofacitinib was 27+ months with 1- and 4-year drug survival rates of 89.6% and 60.2%, respectively, in the UM group. CONCLUSIONS: Although 13.4% of the study population started monotherapy unintentionally, drug survival and remission rates of the UM and combination groups were not different. Comorbidity was a factor affecting transition from combination therapy to monotherapy.

Assessment of lacrimal gland involvement in primary Sjögren's syndrome using gray-scale ultrasonography and shear wave elastography.

OBJECTIVES: The aim of this study was to assess lacrimal gland involvement in primary Sjögren's syndrome (pSS) using lacrimal gland gray-scale ultrasound (LGUS) and two-dimensional shear wave elastography (2D-SWE). METHODS: Eighty-five pSS patients with a mean age of 51.16 ± 10.61 years and 84 sex- and age-matched healthy subjects with a mean age of 50.94 ± 11.05 years were included in the study. Lacrimal gland parenchymal findings and 2D-SWE values were compared between the two groups and the correlations of LGUS parameters with clinical findings, dry eye tests, and minor salivary gland biopsy (MSGB) were further investigated. RESULTS: LGUS parenchymal grade was 0 in 14 (16.5%), 1 in 45 (52.9%), 2 in 23 (27.1%), and 3 in 3 patients (3.5%) in the pSS group, while in the control group, parenchymal grades were 0 (57.1%) and 1 (42.9%). The mean 2D-SWE value of pSS patients was significantly higher than the control group (p < 0.05) and increased parallel with lacrimal parenchymal grade. The elasticity modulus had a high diagnostic performance in detecting lacrimal gland involvement in pSS patients (AUC 0.901, sensitivity 70.6%, specificity 97.6%), while the diagnostic performance of LGUS was much lower (AUC 0.769, sensitivity 83.5%, specificity 57.1%). LGUS and 2D-SWE values were found to be correlated with dry eye tests and MSGB results (p < 0.05). CONCLUSIONS: LGUS and 2D-SWE are both useful for assessing the lacrimal gland involvement in pSS patients; however, 2D-SWE has a better diagnostic performance than LGUS and found to be correlated with dry eye tests. CLINICAL RELEVANCE STATEMENT: Lacrimal gland US and two-dimensional shear wave elastography (2D-SWE) are imaging modalities that can be used to demonstrate parenchymal involvement of the lacrimal gland in primary Sjögren's syndrome (pSS). KEY POINTS: • Gray-scale US and two-dimensional shear wave elastography (2D-SWE) have been widely used in the recent decade to assess gland involvement in patients with primary Sjögren's syndrome (pSS). • The elasticity modulus had a high diagnostic performance in detecting lacrimal gland involvement in primary Sjögren's syndrome (pSS) patients. • Lacrimal gland US and two-dimensional shear wave elastography (2D-SWE) are both useful for assessing the lacrimal gland in primary Sjögren's syndrome (pSS) patients; however, two-dimensional shear wave elastography (2D-SWE) has a better diagnostic performance than lacrimal gland ultrasound (LGUS).

Virtual Reality Headset Simulating a Nature Environment to Improve Health Outcomes in Pregnant Women: A Randomized-Controlled Trial.

The single-blind randomized-controlled experimental study aimed to determine the effects of watching nature images through virtual reality (VR) headset on stress, anxiety, and attachment levels of pregnant women with preterm birth threats (PBTs). The participants were 131 primiparous pregnant women admitted to the perinatology clinic due to PBT between April 5, 2022 and July 20, 2022. The intervention group watched videos containing nature images accompanied by nature sounds in six sessions through VR headset three times daily for 2 days. Each session lasted for 5 min. The data were accumulated with the Information Form, Stress Subscale of Depression Anxiety Stress Scale-21, State Anxiety Inventory, Prenatal Attachment Inventory, and Information Form of Satisfaction Level of VR Headset. State anxiety and stress levels of pregnant women in intervention group were statistically significantly lower than those in controls. There was no difference in prenatal attachment levels concerning intragroup comparisons of intervention group.

Coronavirus Disease 2019-Associated Neurological Manifestations in Children: A Large Single-Center Experience With Rare Cases.

BACKGROUND: We aimed to analyze pediatric patients with coronavirus disease 2019 (COVID-19) with a diverse spectrum of neurological manifestations in a single center since neurological involvement in children is still poorly understood. METHODS: We performed a retrospective study on 912 children aged between zero and 18 years who had a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and symptoms of COVID-19 from March 2020 to March 2021 in a single center. RESULTS: Among 912 patients, 37.5% (n = 342) had neurological symptoms and 62.5% (n = 570) had no neurological symptoms. The mean age of patients with neurological symptoms was significantly higher (14.2 ± 3.7 vs 9.9 ± 5.7; P < 0.001). Three hundred and twenty-two patients had nonspecific symptoms (ageusia, anosmia, parosmia, headache, vertigo, myalgia), whereas 20 patients had specific involvement (seizures/febrile infection-related epilepsy syndrome, cranial nerve palsy, Guillain-Barré syndrome and variants, acute disseminated encephalomyelitis, central nervous system vasculitis). The mean age of the patients with nonspecific neurological symptoms was significantly higher (14.6 ± 3.1 vs 7.7 ± 5.7; P < 0.001). CONCLUSION: This study presents a large number of patients with a diverse spectrum of neurological manifestations. The rare neurological manifestations reported in our study will contribute to better understanding the neurological involvement of SARS-CoV-2 in children. The study also points out the differences of SARS-CoV-2-related neurological manifestations between patients at different ages. Physicians should be alert about recognizing the early neurological manifestations of the SARS-CoV-2 in children.

The Effect of Supportive Care for Pregnant Women During Labor on Breastfeeding Self- Efficacy and the Perception of Childbirth in a Central Region of Turkey.

OBJECTIVE: This study aimed to evaluate the effect of support given to pregnant women during labor on their perception of childbirth and their breastfeeding self-efficacy. METHODS: This descriptive and relational study was conducted with 331 primigravid women who had a vaginal delivery in a maternity unit from December 15, 2018, to March 15, 2020. Data were collected using a descriptive characteristics form prepared by the researcher and based on the relevant literature, the Scale of Women's Perception for Supportive Care Given During Labor (SWPSCDL), the Perception of Birth Scale (POBS), and the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF)." The data were analyzed using descriptive statistics, a t test, a variance test, and Pearson's correlation. RESULTS: The mean total SWPSCDL, POBS, and BSES-SF scores of the participating women were 102.19 (±14.99), 54.75 (±9.39), and 76.24 (±11.37), respectively. A positive correlation was found between supportive care for women during delivery and both women's perceptions of childbirth and breastfeeding efficacy. In addition, training given in antenatal classes positively increased the perception of support during delivery among the women. CONCLUSION: Supportive care given during delivery had a positive effect on the perception of childbirth and on breastfeeding self-efficacy. Interventions to encourage more couples to participate in training given at antenatal classes and to improve the working conditions of midwives working in delivery rooms would contribute to the support that pregnant women require during delivery and would provide a more positive delivery experience for these women.

Urinary Incontinence in Turkish Women: A Qualitative Study on Daily Life and Sexual Health.

PURPOSE: The study was performed to determine how urinary incontinence (UI) affects women's daily lives and sexual health and how UI is perceived. DESIGN: Qualitative descriptive phenomenological design was used. SUBJECTS AND SETTING: The study was conducted in a family health center in Konya, Turkey, with official permission of the ministry of health. Study participants comprised 101 women with UI, but data from 12 women were excluded because they refused to respond to questions; therefore, data analysis is based on responses from 89 respondents. METHODS: Data were compiled via in-depth interviews using a semistructured questionnaire. Data collection and analysis processes were carried out simultaneously. Study data were examined using phenomenological content and thematic analyses. Document portraits and a code map of data were created using qualitative data analysis software. RESULTS: Participants' mean age was 46.25 (SD: 11.68) years. Thirty-three codes were identified to detect the effects of UI on women's daily lives. These codes were reviewed and combined into 5 main themes: religious issues, sexual problems, feeling restricted, psychological exposure, and internalization. CONCLUSIONS: Urinary incontinence causes women to experience environmental, psychological, and religious challenges during daily life. Healthcare professionals should give counsel and assistance by determining the issues for women with UI to promote coping with problems and offer referral for specialist care when necessary.

Mortality in psoriatic arthritis patients, changes over time, and the impact of COVID-19: results from a multicenter Psoriatic Arthritis Registry (PsART-ID).

BACKGROUND: This study aimed to assess the mortality of PsA before and during the COVID-19 pandemic. METHODS: From the prospective, multicenter PsART-ID (Psoriatic Arthritis Registry-International Database), patients from Turkey were analyzed by linking the registry to the Turkish Cause of Death Registry. The outcome of interest was death from any cause, pre-pandemic (since the onset of registry-March 2014-March 2020), and during the pandemic (March 2020-May 2021). The crude mortality rate and standardized mortality ratio (SMR) were determined. RESULTS: There were 1216 PsA patients with a follow-up of 7500 patient-years. Overall, 46 deaths (26 males) were observed. In the pre-pandemic period, SMR for PsA vs the general population was 0.95 (0.61-1.49), being higher in males [1.56 (0.92-2.63)] than females [0.62 (0.33-1.17)]. The crude mortality rate in PsA doubled during the pandemic (pre-pandemic crude mortality rate: 5.07 vs 10.76 during the pandemic) with a higher increase in females (2.9 vs 8.72) than males (9.07 vs 14.73). CONCLUSION: The mortality in PsA was found similar to the general population in the pre-pandemic era. The mortality rates in PsA doubled during the pandemic. Whether PsA patients have more risk of mortality than the general population due to COVID-19 needs further studies. Key Points • Decrease in mortality in PsA might be expected with the more effective treatment options and better disease control. • A crude mortality rate is comparable to the general population and not increased until the pandemic. • Currently, there is a 2-fold increase in crude mortality rate possibly due to the COVID-19.

Impaired kynurenine metabolism in patients with primary Sjögren's syndrome.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is an autoinflammatory disease characterized by inflammation of the exocrine glands. Elevated inflammation causes an increase in kynurenine pathway (KP) metabolite levels by activating indoleamine 2,3-dioxygenase (IDO). The aim of this study was to measure serum KP metabolite concentrations in patients with pSS and to evaluate the relationship between these metabolites with disease activity score and clinical manifestations. DESIGN & METHODS: A total of 80 patients with pSS and 80 healthy controls were enrolled in this study. Serum tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), quinolinic acid (QUIN) concentrations were quantified with liquid chromatography with tandem mass spectrometry (LC-MS/MS). Demographic characteristics, clinical manifestations and disease activity score (ESSDAI) of the participants were recorded. RESULTS: The serum level of KYN and QUIN were significantly higher in patients with pSS with low and moderate activity compared those healthy controls, while the serum level of TRP, KYNA/KYN and 3HK/KYN were lower. In addition, the significant difference for the serum level of KYNA was only in patients with moderate activity from healthy controls, and the difference was higher in favor of pSS patients. Moreover, the KYN/TRP levels were significantly increased with disease activity. The ESSDAI score was positively correlated with KYN/TRP ratio, but negatively correlated with KYNA/KYN ratio. CONCLUSIONS: These findings indicated that KP metabolites may play a role in the etiopathogenesis, activation and progression of pSS.

Comparison of the short-term effects of facemask therapy preceded by conventional rapid maxillary expansion or by an alternate rapid maxillary expansions and constrictions protocol : A retrospective study.

PURPOSE: We aimed to compare the short-term effects of alternate rapid maxillary expansion and constriction (Alt-RAMEC) with conventional rapid maxillary expansion (RME) followed by facemask (FM) therapy. METHODS: A total of 30 patients who had received facemask therapy after RME or Alt-RAMEC protocols were included in the study. The Alt-RAMEC/FM and RME/FM groups were created to be well-matched regarding cervical vertebral maturation stage and sex. In the Alt-RAMEC group (10 males and 5 females, 10.99 ± 1.80 years), expansion screws were activated for a week (two turns/day), then deactivated in the following week (two turns/day). The activation-deactivation protocol continued for 6 or 7 weeks. In the RME/FM group (10 males and 5 females, 11.61 ± 1.20 years), screw activation was performed according to the patients' requirements. Lateral cephalograms which had been taken at the beginning of treatment and at the end of the facemask therapy were analyzed. Intragroup and intergroup differences were statistically analyzed. RESULTS: Both groups showed a significant sagittal advancement of the maxilla. However, the Alt-RAMEC/FM group showed statistically greater improvements than the RME/FM group for SNA (3.11 ± 1.79 vs. 1.45 ± 1.34, p = 0.008), ANB (4.29 ± 1.80 vs. 2.95 ± 1.19, p = 0.023), convexity (8.91 ± 4.29 vs. 5.61 ± 2.51, p = 0.016), and overjet (5.86 ± 2.29 vs. 4.61 ± 2.10, p < 0.001). The sagittal mandibular, vertical skeletal, dental, and soft tissue changes were similar between the groups (p > 0.05). CONCLUSION: The Alt-RAMEC protocol was found to be more effective in the correction of skeletal class III malocclusion in the short term.