Human SRY expression at the sex-determining period is insufficient to drive testis development in mice

Endocrinology ◽  
2021 ◽  
Author(s):  
Atsumi Tsuji-Hosokawa ◽  
Yuya Ogawa ◽  
Iku Tsuchiya ◽  
Miho Terao ◽  
Shuji Takada
Keyword(s):  
Mouse Model ◽  
Y Chromosome ◽  
Initiation Factor ◽  
Reading Frame ◽  
Testis Development ◽  
Significant Difference ◽  
Exon 1 ◽  
The Difference ◽  
Cortical Regions ◽  
Species Specific

Abstract The sex-determining region of the Y chromosome, Sry/SRY, is an initiation factor for testis development in both humans and mice. Although the functional compatibility between murine SRY and human SRY was previously examined in transgenic mice, their equivalency remains inconclusive. As molecular interaction and timeline of mammalian sex determination were mostly described in murine experiments, we generated a mouse model in which Sry was substituted with human SRY to verify the compatibility. The mouse model had the human SRY open reading frame at the locus of murine Sry exon 1 (Sry  (SRY) mice) and was generated using the CRISPR/Cas9 system. The reproductive system of the mice was analyzed. The expression of human SRY in the fetal gonadal ridge of Sry  (SRY) mice was detected. The external and internal genitalia of adult Sry  (SRY) mice were similar to those of wild-type females, without any significant difference in anogenital distance. Sry  (SRY) mice obtained gonads, which were morphologically considered as ovaries. Histological analysis revealed that the cortical regions of gonads from adult Sry  (SRY) mice contained few follicles. We successfully replaced genes on the Y chromosome with targeted genome editing using the CRISPR/Cas9 system. Since the Sry  (SRY) XY mice did not develop testis, we concluded that human SRY was insufficient to drive testis development in mouse embryos. The difference in response elements and lack of glutamine-rich domains may have invalidated human SRY function in mice. Signal transduction between Sry/SRY expression and Sox9/SOX9 activation is possibly organized in a species-specific manner.

Leukemogenesis of the b2a2 Type p210 BCR/ABL in a Bone Marrow Transplantation Mouse Model Using a Lentivirus Vector.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2875-2875
Author(s):  
Naoya Uchida ◽  
Hideki Hanawa ◽  
Koiti Inokuchi ◽  
Kazuo Dan ◽  
Takashi Shimada
Keyword(s):  
Bone Marrow ◽  
Mouse Model ◽  
Peripheral Blood ◽  
Chronic Phase ◽  
Hemoglobin Concentration ◽  
Retroviral Vectors ◽  
Myeloproliferative Disease ◽  
Significant Difference ◽  
The Difference ◽  
Lentivirus Vectors

Abstract [INTRODUCTION] BCR/ABL induces the chronic phase of chronic myeloid leukemia (CML). The three main principal forms (p190, p210 and p230 BCR/ABL) of the BCR/ABL gene are found in distinct forms of leukemia and have shown to be different leukemogenic activities in mice. The BCR breakpoint locations of p210 BCR/ABL falls either between the exons b2 and b3 (b2a2) or between the exons b3 and b4 (b3a2). Though the leukemogenic activity of the b3a2 type gene had been shown in mice, the leukemogenesis of the b2a2 type has not been tested yet. [PURPOSE] The purpose of this study is to evaluate the leukemogenesis of the b2a2 p210 BCR/ABL gene, for the first time, in a bone marrow (BM) transduction and transplantation (BMTT) mouse model, and to compare the leukemogenesis of the b2a2 and the b3a2 p210 BCR/ABL. [METHODS] The ecotropic envelope-pseudotyped self-inactivating lentivirus vectors carrying the b2a2 or the b3a2 p210 BCR/ABL cDNA driven by the murine stem cell virus (MSCV) U3 promoter was constructed. The BM cells were harvested from Balb/c mice without 5-fluorouracil pretreatment. The lineage-marker-negative (Lin−) BM cells were prepared by negative selections using a lineage antibodies cocktail (anti-mouse CD3e, CD11b, B220, Gr-1 and TER-119). The Lin− BM cells were prestimulated by cytokines (mIL3, mSCF, hTPO, hIL6) and then these were transduced for 12 hrs with the lentivirus vectors at a MOI (multiplicity of infection) 3 in the presence of the same cytokines on a RetroNectin (TAKARA)-coated 6-well plate. The initial transduction rates of the b2a2 and the b3a2 p210 BCR/ABL vectors were 0.38% and 0.16%, respectively, determined by real time PCR. The transduced BM cells (1 x 105) were transplanted by injection into the lateral tail vein of the lethally irradiated Balb/c mice. [RESULT] In our BMTT mouse model, both the b2a2 and the b3a2 p210 BCR/ABL genes developed a fatal CML-like myeloproliferative disease in 4 weeks after transplantation. The frequency of leukemia development with the b2a2 was 75% (6/8), while that with the b3a2 was 30% (3/10). The difference may depend on the initial transduction rate. The disease was characterized by expansion of mature myeloid cells in peripheral blood. The averaged copy-number of the vector in peripheral blood cells in leukemic mice (> 0.1 copy/diploid) was higher than that in leukemia-free mice (< 0.03 copy/diploid). There was no significant difference between the phenotypes of the b2a2 and the b3a2 p210 BCR/ABL genes, in white blood cell count (41.2±15.2 vs. 38.5±7.00 x103/mm3, p=.907), hemoglobin concentration (13.5±0.642 vs. 13.9±1.13 g/dl, p=.779) and platelet count (646±74.0 vs. 460±60.4 x103/mm3, p=.152). The survival time of each CML-like mice was also similar (57±6 vs. 62±15 days, p=.534). [DISCUSSION] Our BMTT model mice using lentivirus vectors survived longer (Mean: 58±5, Median: 48±2 days) than the previous BMTT model mice using retroviral vectors. Therefore our BMTT mouse model using the lentivirus vectors is more likely to mimic a human CML than using retroviral vectors. Using this model, the fatal CML-like myeloproliferative disease was developed with the b2a2 p210 BCR/ABL gene as well as the b3a2 gene. These data suggest the b2a2 p210 BCR/ABL had similar leukemogenic activities to the b3a2.

scholarly journals Detailed genetic and functional analysis of the hDMDdel52/mdx mouse model

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244215
Author(s):  
Alper Yavas ◽  
Rudie Weij ◽  
Maaike van Putten ◽  
Eleni Kourkouta ◽  
Chantal Beekman ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mrna Level ◽  
Exon Skipping ◽  
Neuromuscular Disorder ◽  
Motor Deficit ◽  
Mdx Mouse ◽  
Transcription Activator ◽  
Reading Frame ◽  
New Findings ◽  
Significant Difference

Duchenne muscular dystrophy (DMD) is a severe, progressive neuromuscular disorder caused by reading frame disrupting mutations in the DMD gene leading to absence of functional dystrophin. Antisense oligonucleotide (AON)-mediated exon skipping is a therapeutic approach aimed at restoring the reading frame at the pre-mRNA level, allowing the production of internally truncated partly functional dystrophin proteins. AONs work in a sequence specific manner, which warrants generating humanized mouse models for preclinical tests. To address this, we previously generated the hDMDdel52/mdx mouse model using transcription activator like effector nuclease (TALEN) technology. This model contains mutated murine and human DMD genes, and therefore lacks mouse and human dystrophin resulting in a dystrophic phenotype. It allows preclinical evaluation of AONs inducing the skipping of human DMD exons 51 and 53 and resulting in restoration of dystrophin synthesis. Here, we have further characterized this model genetically and functionally. We discovered that the hDMD and hDMDdel52 transgene is present twice per locus, in a tail-to-tail-orientation. Long-read sequencing revealed a partial deletion of exon 52 (first 25 bp), and a 2.3 kb inversion in intron 51 in both copies. These new findings on the genomic make-up of the hDMD and hDMDdel52 transgene do not affect exon 51 and/or 53 skipping, but do underline the need for extensive genetic analysis of mice generated with genome editing techniques to elucidate additional genetic changes that might have occurred. The hDMDdel52/mdx mice were also evaluated functionally using kinematic gait analysis. This revealed a clear and highly significant difference in overall gait between hDMDdel52/mdx mice and C57BL6/J controls. The motor deficit detected in the model confirms its suitability for preclinical testing of exon skipping AONs for human DMD at both the functional and molecular level.

Cranial crassicaudiasis in two coastal dolphin species from South Africa is predominantly a disease of immature individuals

2020 ◽  
Vol 139 ◽  
pp. 93-102 ◽  
Author(s):  
MF Van Bressem ◽  
P Duignan ◽  
JA Raga ◽  
K Van Waerebeek ◽  
N Fraijia-Fernández ◽  
...  
Keyword(s):  
South Africa ◽  
Bone Development ◽  
Bottlenose Dolphins ◽  
Fatal Outcome ◽  
Population Level ◽  
Cape Coast ◽  
Osteolytic Lesions ◽  
Immune Mediated ◽  
Significant Difference ◽  
The Difference

Crassicauda spp. (Nematoda) infest the cranial sinuses of several odontocetes, causing diagnostic trabecular osteolytic lesions. We examined skulls of 77 Indian Ocean humpback dolphins Sousa plumbea and 69 Indo-Pacific bottlenose dolphins Tursiops aduncus, caught in bather-protecting nets off KwaZulu-Natal (KZN) from 1970-2017, and skulls of 6 S. plumbea stranded along the southern Cape coast in South Africa from 1963-2002. Prevalence of cranial crassicaudiasis was evaluated according to sex and cranial maturity. Overall, prevalence in S. plumbea and T. aduncus taken off KZN was 13 and 31.9%, respectively. Parasitosis variably affected 1 or more cranial bones (frontal, pterygoid, maxillary and sphenoid). No significant difference was found by gender for either species, allowing sexes to be pooled. However, there was a significant difference in lesion prevalence by age, with immature T. aduncus 4.6 times more likely affected than adults, while for S. plumbea, the difference was 6.5-fold. As severe osteolytic lesions are unlikely to heal without trace, we propose that infection is more likely to have a fatal outcome for immature dolphins, possibly because of incomplete bone development, lower immune competence in clearing parasites or an over-exuberant inflammatory response in concert with parasitic enzymatic erosion. Cranial osteolysis was not observed in mature males (18 S. plumbea, 21 T. aduncus), suggesting potential cohort-linked immune-mediated resistance to infestation. Crassicauda spp. may play a role in the natural mortality of S. plumbea and T. aduncus, but the pathogenesis and population level impact remain unknown.

Perbedaan Penggunaan Antikoagulan K2EDTA DAN K3EDTA Terhadap Hasil Pemeriksaan Indeks Eritrosit

2018 ◽  
Vol 1 (2) ◽  
pp. 114
Author(s):  
Wahdaniah Wahdaniah ◽  
Sri Tumpuk
Keyword(s):  
Screening Test ◽  
Venous Blood ◽  
The Body ◽  
Ethylene Diamine ◽  
P Value ◽  
Cross Sectional ◽  
Significant Difference ◽  
Ethylene Diamine Tetra Acetate ◽  
The Difference ◽  
Index Value

Abstract: Routine blood examination is the earliest blood test or screening test to determine the diagnosis of an abnormality. Blood easily froze if it is outside the body and can be prevented by the addition of anticoagulants, one of which Ethylene Diamine Tetra Acetate (EDTA). Currently available vacuum tubes containing EDTA anticoagulants in the form of K2EDTA and K3EDTA. K3EDTA is usually a salt that has better stability than other EDTA salts because it shows a pH approaching a blood pH of about 6.4. The purpose of this research is to know the difference of erythrocyte index results include MCH, MCV and MCHC using K3EDTA anticoagulant with K2EDTA. This research is a cross sectional design. This study used venous blood samples mixed with K2EDTA anticoagulant and venous blood mixed with K3EDTA anticoagulants, each of 30 samples. Data were collected and analyzed using paired different test. Based on data analysis that has been done on MCH examination, p value <0,05 then there is a significant difference between samples with K3EDTA anticoagulant with K2EDTA to erythrocyte index value. Then on the examination of MCV and MCHC obtained p value <0.05 then there is no significant difference between samples with K3EDTA anticoagulant with K2EDTA to erythrocyte index value.Abstrak: Pemeriksaan darah rutin merupakan pemeriksaan darah yang paling awal atau screening test untuk mengetahui diagnosis suatu kelainan. Darah mudah membeku jika berada diluar tubuh dan bisa dicegah dengan penambahan antikoagulan, salah satunya Ethylene Diamine Tetra Acetate (EDTA). Dewasa ini telah tersedia tabung vakum yang sudah berisi antikoagulan EDTA dalam bentuk  K2EDTA dan  K3EDTA. K3EDTA  biasanya berupa garam yang mempunyai stabilitas yang lebih baik dari garam EDTA yang lain karena menunjukkan pH yang mendekati pH darah yaitu sekitar 6,4. Tujuan dari penelitian ini adalah untuk mengetahui perbedaan hasil indeks eritrosit meliputi MCH, MCV dan MCHC menggunakan antikoagulan K3EDTA dengan K2EDTA. Penelitian ini merupakan penelitian dengan desain cross sectional. Penelitian ini menggunakan sampel darah vena yang dicampur dengan antikoagulan K2EDTA dan darah vena yang dicampur dengan antikoagulan K3EDTA, masing-masing sebanyak 30 sampel. Data dikumpulkan dan dianalisis menggunakan uji beda berpasangan. Berdasarkan analisis data yang telah dilakukan pada pemeriksaan MCH didapatkan nilai p < 0,05 maka ada perbedaan yang signifikan antara sampel dengan antikoagulan K3EDTA dengan K2EDTA terhadap nilai indeks eritrosit. Kemudian pada pemeriksaan MCV dan MCHC didapatkan nilai p < 0,05 maka tidak ada perbedaan yang signifikan antara sampel dengan antikoagulan K3EDTA dengan K2EDTA terhadap nilai indeks eritrosit.

Pengaruh Jumlah Pencucian Beras dengan Kadar Klorin

2017 ◽  
Vol 1 (1) ◽  
pp. 89
Author(s):  
Indah Purwaningsih ◽  
Supriyanto Supriyanto
Keyword(s):  
Mucous Membrane ◽  
Confidence Level ◽  
Iodometric Titration ◽  
Titration Method ◽  
Anova Test ◽  
Average Value ◽  
Significant Difference ◽  
The Difference

Abstract: Chlorine is a green halogen-shaped halogen gas at normal temperature and serves as bleach, stain remover and disinfectant. Chlorine is now widely used for bleaching rice so that less quality rice looks like quality rice. Chlorine is very toxic and causes mucous membrane irritation, highly reactive and very powerful oxidizer. The purpose of this research was to determine the difference of chlorine level in chlorinated rice washed once, twice and 3 times. The sample in this study amounted to 11 samples calculated by replication formula. Each sample was treated 3 times, ie 1 washed once, 2 washed twice and washed 3 times. The samples then examined by iodometric titration method. Based on the results of the study using ANOVA test, 11 samples obtained the average value of chlorine after washed once amount of 0.0176%, after washed twice amount of 0.0111%, and after washed 3 times amount of 0.0052% with the value significance p = 0.03 (p <0.05) at 95% confidence level which means there was a significant difference between chlorine levels in chlorinated rice washed once, twice and 3 times.Abstrak: Klorin merupakan unsur halogen berbentuk gas berwarna kuning kehijauan pada suhu normal danberfungsi sebagai pemutih, penghilang noda maupun desinfektan. Klorin sekarang banyak digunakan untuk bahan pemutih beras agar beras yang kurang berkualitas tampak seperti beras berkualitas. Klorin sangat toksik dan menyebabkan iritasi membran mukosa, sangat reaktif dan merupakan oksidator yang sangat kuat. Tujuan dari penelitian ini ialah untuk mengetahui perbedaan kadar klorin pada beras berklorin yang dicuci sebanyak 1 kali, 2 kali dan 3 kali. Sampel dalam penelitian ini berjumlah 11 sampel yang dihitung dengan rumus replikasi. Setiap sampel diberi perlakuan sebanyak 3 kali, yaitu 1 kali pencucian, 2 kali pencucian dan 3 kali pencucian. Sampel penelitian kemudian diperiksa dengan metode titrasi iodometri. Berdasarkan hasil penelitian menggunakan uji Anova secara komputerisasi terhadap 11 sampel diperoleh nilai rata-rata kadar klorin setelah 1 kali pencucian sebesar 0,0176 %, setelah 2 kali pencucian sebesar 0,0111 %, dan setelah 3 kali pencucian sebesar 0,0052 % dengan nilai signifkansi p = 0,03 (p<0,05) pada tingkat kepercayaan 95% yang artinya ada perbedaan yang bermakna antara kadar klorin pada beras berklorin yang dicuci sebanyak 1 kali, 2 kali dan 3 kali.

P-Removal in Completely Mixed Systems

1985 ◽  
Vol 17 (11-12) ◽  
pp. 325-326 ◽  
Author(s):  
H J. G. W. Donker ◽  
P. Opic ◽  
H. P. de Vries
Keyword(s):  
Mixed System ◽  
Domestic Waste ◽  
Recirculation Flow ◽  
Start Up ◽  
Significant Difference ◽  
Aerobic Reactor ◽  
The Difference ◽  
Positive Effect ◽  
Mixed Systems ◽  
P Removal

Ca. 60 % of the Dutch activated sludge plants consist of completely mixed systems, experiments have been carried out in completely mixed pilot plants to study the biological P-removal. The research was carried out in two pilot plants. The pilot plants consisted of: anaerobic reactor, anoxic reactor, aerobic reactor and a clarifier. All the reactors were completely mixed. Both plants were fed with settled domestic waste water at a sludge loading of 400 and 250 g COD/kg sludge.day respectively. The results are given below:sludge loading (g COD/kg sludge.day)400400250ratio Anaerobic : Anoxic : Aerobic1: 1:2,71:1:4,11:1:2,7P-removal (%)802875N-removal (%)505065COD-removal (%)858585 It has been shown that there is no significant difference between the results at the two different sludge loadings. Remarkable is the difference between the ratio 1:1:2,7 in combination with the internal recirculation flow anoxic-anaerobic of 160 % and the ratio 1:1:4,1 with a recirculation flow of 30 %. During the start-up at a sludge loading of 250 g COD/kg sludge.day and an internal recirculation flow of 30 %, bulking sludge developed almost immediately. The Premoval was completely disturbed. Increasing the internal recirculation flow to 160% had a positive effect on settling properties and P-removal. This investigation has pointed out that a completely mixed system is suitable for biological P-removal, without negatively affecting the nitrification. Important factors in the process are the ratio anaerobic:anoxic:aerobic and the recirculation flows.

Effect of Levetiracetam on Cognitive Function and Clonic Seizure Frequency in Children with Epilepsy

2019 ◽  
Vol 19 (9) ◽  
pp. 699-703
Author(s):  
Shihao Zhou ◽  
Qiong Zhan ◽  
Xiaomei Wu
Keyword(s):  
Cognitive Function ◽  
Effective Rate ◽  
Clonic Seizure ◽  
Conventional Group ◽  
Significant Difference ◽  
Random Number Table ◽  
Clonic Seizures ◽  
The Difference ◽  
Experimental Group ◽  
Executive Ability

Background: This study aimed to explore the clinical effect of levetiracetam in the treatment of children with epilepsy. Methods: 136 children with epilepsy were selected from January 2017 to December 2017. According to the random number table method, they were divided into the experimental group and the conventional group, with 68 cases in each group. The conventional group was treated with valproate, while the experimental group was treated with levetiracetam. The effective rate, the cognitive function and the frequency of clonic seizures in the two groups were compared. Results: There was no significant difference in the total effective rate between the two groups (P>0.05). There was no significant difference in attention, executive ability, abstract and orientation scores between the two groups before treatment (P>0.05). After treatment, the focus of attention (106.54±6.56), executive ability (105.76±6.77), abstract and directional score (106.65±6.57) were significantly higher than that of the conventional group. The difference in the two groups was statistically significant (P<0.05). After 3 months of treatment, the frequency of myoclonic seizures (9.22±0.95) and the frequency of tonic-clonic seizures (11.68±1.36) were found to be significantly lower than those of the conventional group, and the difference between the two groups was statistically significant (P<0.05). Conclusion: Levetiracetam is effective in the treatment of children with epilepsy. It can effectively improve the cognitive function of the patients, reduce the frequency of myoclonic seizures and tonic-clonic seizures, and has a high promotion value.

Stability and mutual impact of perception of parental pressure and infants' social support – A study based on the difference between employment status and household income

2021 ◽  
pp. 002072092199705
Author(s):  
Yong Wang
Keyword(s):  
Household Income ◽  
Employment Status ◽  
Working Mothers ◽  
Social Research ◽  
Research Report ◽  
Parental Pressure ◽  
Income Levels ◽  
Significant Difference ◽  
The Difference ◽  
The Stability

The purpose of this study is to explore the stability and interaction between parental pressure and social research report, as well as the role of employment status and family income levels in this process. This study used a special study on Korean children (PSKC) 2–4 waves. Use t-test, correlation and autoregressive cross-delay modeling to analyze the data. The main findings of this study are: First, over time, parental pressure and mother’s social research report are consistent. Secondly, the pressure of motherhood and childcare has an obvious lagging effect on upbringing, and vice versa. Third, there is no significant difference between working mothers and non-working mothers in terms of the stability of working parents' pressure, social research report and social research report for children's pressure channels. However, parental pressure can only predict the social research report of working mothers. Fourth, there is no significant difference between the stability and interaction of these two structures in household income levels. In short, the results show that, over time, parental pressure is consistent with mother’s social research report. The results also show that there is a significant cross-lag effect between the mothers’ perceptions of mutual pressure analysis. In the process from parental pressure to social research report, I found the difference between working and non-working mothers. The advantage of this study is that the expected longitudinal design was adopted during infancy and the priority between the two structures can be considered. The results of this study can be used as a source of intervention plans to help parents withstand severe parenting pressure and lack of social research report.

scholarly journals Responses of Bat Communities (Mammalia: Chiroptera) to Forest Loss and Habitat Conversion in Southern Cameroon

2021 ◽  
Vol 14 ◽  
pp. 194008292110103
Author(s):  
Patrick Jules Atagana ◽  
Eric Moïse Bakwo Fils ◽  
Sevilor Kekeunou
Keyword(s):  
Secondary Forest ◽  
Biosphere Reserve ◽  
Abundant Species ◽  
Primary Forest ◽  
Habitat Types ◽  
Habitat Transformation ◽  
Significant Difference ◽  
Southern Cameroon ◽  
Habitat Conversion ◽  
Species Specific

We aimed to assess how bats are affected by habitat transformation by comparing bat assemblages in four habitat types: primary forest, secondary forest, cocoa plantations and human habitations in the Dja Biosphere Reserve of southern Cameroon. Bats were sampled in the four habitat types using mist nets. During 126 nights, a total of 413 bats were captured, belonging to four families, 16 genera and 24 species. Ninety three individuals (17 species) were captured in the primary forest, followed by plantations (105 individuals, 14 species), human habitations (159 individuals, 10 species), and secondary forest (55 individuals, eight species). Megaloglossus woermanni was recorded in all the four habitats, and was the most abundant species (105 individuals). The analysis of bat assemblage between habitat types showed a statistically significant difference in species composition. The distribution of the six most abundant species ( Epomops franqueti, Megaloglossus woermanni, Rousettus aegyptiacus, Dohyrina cyclops, Hipposideros cf. caffer and Hipposideros cf. ruber) was influenced by habitat types. Our results suggest that the decrease in species richness observed in disturbed habitats may be due to habitat perturbations of primary forest habitats. Therefore, it is important to examine the effects of habitat conversion at species level, as responses are often species-specific.

scholarly journals POS0208 GENDER DIFFERENCES IN RESPONSE TO BIOLOGICALS. WOMEN FARE WORSE ACROSS INFLAMMATORY ARTHRITIS DISEASES - DATA FROM THE BIOREG

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 320.1-321
Author(s):  
E. Loibner ◽  
V. Ritschl ◽  
B. Leeb ◽  
P. Spellitz ◽  
G. Eichbauer-Sturm ◽  
...  
Keyword(s):  
Gender Differences ◽  
Psoriatic Arthritis ◽  
Gender Difference ◽  
Disease Activity ◽  
Inflammatory Arthritis ◽  
Tnf Inhibitors ◽  
Significant Difference ◽  
The Difference ◽  
All Diseases

Background:Gender differences in prevalence and disease course are known in various rheumatic diseases; however, investigations of gender difference concerning therapeutical response have yielded variable results.Objectives:The aim of this retrospective study was to investigate, whether a gender difference in response rate to biological disease-modifying antirheumatic drugs (bDMARDs) and apremilast in bDMARD-naïve patients could be observed across the three most prevalent inflammatory arthritis diseases: rheumatoid arthritis (RA), spondylarthritis (SpA) and psoriatic arthritis (PsA). Additionally, a response to individual TNF blockers was investigated in this respect.Methods:Data from bDMARD-naïve RA-, SpA- and PsA-patients from Bioreg, the Austrian registry for biological DMARDs in rheumatic diseases, were used. Patients with a baseline (Visit 1=V1) and follow-up visits at 6 months (Visit 2=V2) and 12 months (Visit 3=V3) were included and response to therapy with TNF-inhibitors (TNFi), furthermore to therapy with rituximab, tocilizumab and apremilast was analyzed according to gender. The remaining bDMARDs were not analyzed due to small numbers. Key response-parameter for RA was disease activity score (DAS28), whereas for PsoA the Stockerau Activity Score for Psoriatic Arthritis (SASPA) and for SpA the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were employed; in addition, the Health assessment Questionnaire (HAQ) was used. Data were analyzed in R Statistic stratified by gender using Kruskal-Wallis and Wilcoxon tests.Results:354 women and 123 men with RA (n=477), 81 women and 69 men with PsA (n=150), 121 women and 191 men with SpA (n=312) were included. No significant differences in biometrics was seen between female and male patients at baseline in all diseases.In RA patients overall DAS28 decreased from baseline (V1) to V2 and V3 (DAS28: V1: male: 4.38 [3.66, 5.11], female: 4.30 [3.68, 5.03], p(m/f) = 0.905; V2: male: 2.66 [1.73, 3.63], female: 3.10 [2.17, 3.98], p(m/f) = 0.015; V3: male: 2.25 [1.39, 3.36], female: 3.01 [1.87, 3.87], p(m/f) = 0.002). For TNF inhibitors (n=311), there was a significant difference between genders at V2 (Fig.1a). Patients receiving Rituximab (n=41) displayed a significantly higher DAS28 at baseline in females, which diminished in the follow up: V1: (p(m/f) p=0.002; V2: p=0.019; V3: p=0.13); response to tocilizumab (n=63) did not show any gender differences.In PsA patients overall SASPA decreased from baseline (V1) to V2 and V3 (SASPA: V1: male: 4.00 [2.80, 5.20], female: 4.40 [2.80, 5.80], p(m/f) = 0.399; V2: male: 2.20 [1.20, 3.50], female: 3.40 [2.00, 5.00], p(m/f) = 0.071; V3: male: 1.80 [0.80, 2.70], female: 3.01 [2.35, 4.80], p(m/f) = 0.001). For TNF inhibitors (n=79), there was a significant difference between genders at V3 (Fig 1a). For Apremilast (n=39), there was a significant difference between genders at V2 (Fig.1c).In SpA patients overall BASDAI decreased from baseline (V1) to V2 and V3 (BASDAI: V1: male: 4.70 [2.88, 6.18], female: 4.80 [3.30, 6.20], p(m/f) = 0.463; V2: male: 3.05 [2.00, 4.60], female: 3.64 [2.62, 5.41], p(m/f) = 0.039; V3: male: 3.02 [1.67, 4.20], female: 3.65 [2.18, 5.47], p(m/f) = 0.016). In V3 a differential BASDAI in response to TNFi (n=299) was observed (Fig.1a).Possible differences of response to individual TNFi (etanercept, infliximab, other TNFi) measured by HAQ were investigated in all diseases together. The difference between male and females was significant at baseline for all 3 TNFi; whereas with the use of ETA the significant difference was carried through to V2 and V3, it was lost with the use of IFX and was variable with the other TNFi (Fig.1b)Figure 1.Conclusion:Female patients showed a statistically lower response to TNFi in all three disease entities (RA, SpA and PsoA) to a variable degree in our homogenous central european population. Interestingly, the difference was not uniform across individual TNFi when measured by HAQ. Gender differences were also seen in response to Apremilast.Disclosure of Interests:Elisabeth Loibner: None declared, Valentin Ritschl: None declared, Burkhard Leeb Speakers bureau: AbbVie, Roche, MSD, Pfizer, Actiopharm, Boehringer-Ingelheim, Kwizda, Celgene, Sandoz, Grünenthal, Eli-Lilly, Grant/research support from: TRB, Roche, Consultancies: AbbVie, Amgen, Roche, MSD, Pfizer, Celgene, Grünenthal, Kwizda, Eli-Lilly, Novartis, Sandoz;, Peter Spellitz: None declared, Gabriela Eichbauer-Sturm: None declared, Jochen Zwerina: None declared, Manfred Herold: None declared, Miriam Stetter: None declared, Rudolf Puchner Speakers bureau: AbbVie, BMS, Janssen, Kwizda, MSD, Pfizer, Celgene, Grünenthal, Eli-Lilly, Consultant of: AbbVie, Amgen, Pfizer, Celgene, Grünenthal, Eli-Lilly, Franz Singer: None declared, Ruth Fritsch-Stork: None declared

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