Expanded T lymphocytes in the cerebrospinal fluid of multiple sclerosis patients are specific for Epstein-Barr-virus-infected B cells.

Epstein-Barr virus (EBV) infection has long been associated with multiple sclerosis (MS), but the role of EBV in the pathogenesis of MS is not clear. Our hypothesis is that a major fraction of the expanded clones of T lymphocytes in the cerebrospinal fluid (CSF) are specific for autologous EBV-infected B cells. We obtained blood and CSF samples from eight relapsing-remitting patients in the process of diagnosis. We stimulated cells from the blood with autologous EBV-infected lymphoblastoid cell lines (LCL), EBV, varicella zoster virus, influenza, and candida and sorted the responding cells with flow cytometry after 6 d. We sequenced the RNA for T cell receptors (TCR) from CSF, unselected blood cells, and the antigen-specific cells. We used the TCR Vß CDR3 sequences from the antigen-specific cells to assign antigen specificity to the sequences from the CSF and blood. LCL-specific cells comprised 13.0 ± 4.3% (mean ± SD) of the total reads present in CSF and 13.3 ± 7.5% of the reads present in blood. The next most abundant antigen specificity was flu, which was 4.7 ± 1.7% of the reads in the CSF and 9.3 ± 6.6% in the blood. The prominence of LCL-specific reads was even more marked in the top 1% most abundant CSF clones with statistically significant 47% mean overlap with LCL. We conclude that LCL-specific sequences form a major portion of the TCR repertoire in both CSF and blood and that expanded clones specific for LCL are present in MS CSF. This has important implications for the pathogenesis of MS.

Clinical and diagnostic findings in COVID-19 patients: an original research from SG Moscati Hospital in Taranto Italy.

The coronavirus disease 2019 (COVID-19) pandemic is a worldwide medical challenge due to the scarcity of proper information and remedial resources. The ability to efficiently avoid a further SARS-CoV-2 pandemic will, therefore, depend on understanding several factors which include host immunity, virus behavior, prevention measures, and new therapies. This is a multi-phase observatory study conducted in the SG Moscati Hospital of Taranto in Italy that was converted into COVID-19 Special Care Unit for SARS-Co-V2 risk management. Patients were admitted to the 118 Emergency Pre-Hospital and Emergency Department based on two diagnostic criteria, the nasopharyngeal swab assessed by reverse-transcriptase-polymerase-chain-reaction (RT-PCR) and CT-scan image characterized by ground glass opacity. Patients were divided into four groups, positive-positive (ER-PP), negative-positive (ER-NP), negative-negative (ER-NN) and a group admitted to the ICU (ER-IC). A further control group was added when the T and B lymphocyte subsets were analyzed. Data included gender, age, vital signs, arterial blood gas analysis (ABG), extensive laboratory results with microbiology and bronchoalveolar lavage fluid (BALF) which were analyzed and compared. Fundamental differences were reported among the groups. Males were significantly higher in PP, ICU, and NP groups, from 2 to 4-fold higher than females, while in the NN group, the number of females was mildly higher than males; the PP patients showed a marked alkalotic, hypoxic, hypocapnia ABG profile with hyperventilation at the time of admission; finally, the laboratory and microbiology results showed lymphopenia, fibrinogen, ESR, CRP, and eGFR were markedly anomalous. The total number of CD4+ and CD8+ T cells was dramatically reduced in COVID-19 patients with levels lower than the normal range delimited by 400/µL and 800/µL, respectively, and were negatively correlated with blood inflammatory responses.

Fluorescent Properties of Carboxyfluorescein Bifluorophores.

Bright fluorescent probes with enhanced intensities in the fluorescein channel are of great value for plenty of biological applications. To design effective probes one should introduce as many as possible fluorophores to the biomolecule while leaving its native structure as intact as possible. To reach this compromise, we designed and synthesized fluorescein bifluorophores on the 3,5-diaminobenzoic acid scaffold, which allows for insertion of two fluorophores at one modification site of a biomolecule. Rigid structure of the branching linker group allows to minimize self-quenching the fluorophores. However, despite the structure similarities of fluorescein isomers (5-FAM and 6-FAM), different photophysical behavior was observed for the corresponding bifluorophores. Here we made efforts to get insight into these effects with the focus on the media viscosity impact.

Cooperative improvement in growth rate, red-colour score and astaxanthin level of white-leg shrimp by Bacillus strains originating from shrimp gut.

AIMS: We investigated the potential cooperative effects of carotenoid-producing Bacillus aquimaris SH6 and nonpigmented Bacillus subtilis SH23 on white-leg shrimp growth and health. METHODS AND RESULTS: SH6, SH23 and a combination of both spores (1 × 106  CFU per g pellet) were administered in shrimp. The growth rate (2·36% day-1 ), red-colour score (25) and astaxanthin concentration (3·5 µg g-1 shrimp) were maximum in two-spore-administered shrimp. Immune-related Rho mRNA expression level and phenoloxidase and superoxidase dismutase activities were higher in two-spore-administered shrimp than in control shrimp, with Rho mRNA expression level being 55-fold higher in two-spore-administered shrimp than in SH6-administered shrimp and phenoloxidase activity being 1·2-fold higher in two-spore-administered shrimp than in SH23-administered shrimp. Although live SH6 count was 2·7-fold lower, SH6 germination level was 3·5-fold higher in the combination group than in SH6 group. CONCLUSIONS: When both SH6 and SH23 spores were administered, SH6 spore germination was enhanced and cooperative improvement was seen in growth, astaxanthin level and red-colour score of white-leg shrimp; however, immune-related parameters were induced in a noncooperative manner. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report showing the cooperative probiotic activities of Bacillus strains and their possible mechanisms in a shrimp model.

Sensory trait variation contributes to biased dispersal of threespine stickleback in flowing water.

Gene flow is widely thought to homogenize spatially separate populations, eroding effects of divergent selection. The resulting theory of 'migration-selection balance' is predicated on a common assumption that all genotypes are equally prone to dispersal. If instead certain genotypes are disproportionately likely to disperse, then migration can actually promote population divergence. For example, previous work has shown that threespine stickleback (Gasterosteus aculeatus) differ in their propensity to move up- or downstream ('rheotactic response'), which may facilitate genetic divergence between adjoining lake and stream populations of stickleback. Here, we demonstrate that intraspecific variation in a sensory system (superficial neuromast lines) contributes to this variation in swimming behaviour in stickleback. First, we show that intact neuromasts are necessary for a typical rheotactic response. Next, we showed that there is heritable variation in the number of neuromasts and that stickleback with more neuromasts are more likely to move downstream. Variation in pectoral fin shape contributes to additional variation in rheotactic response. These results illustrate how within-population quantitative variation in sensory and locomotor traits can influence dispersal behaviour, thereby biasing dispersal between habitats and favouring population divergence.

Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia.

VM202, a plasmid DNA that expresses two isoforms of hepatocyte growth factor, may elicit angiogenic effects that could benefit patients with critical limb ischemia (CLI). In a phase 2, double-blind trial in 52 CLI patients, we examined the safety and potential efficacy of intramuscular injections of low-dose (n=21) or high-dose (n=20) VM202 or placebo (n=11) in the affected limb (days 0, 14, 28 and 42). Adverse events and serious adverse events were similar among the groups; no malignancy or proliferative retinopathy was seen. In exploratory efficacy analyses, we found no differences in ankle or toe-brachial index, VAS, VascuQuol or amputation rate among the groups. Complete ulcer healing was significantly better in high-dose (8/13 ulcers; P<0.01) versus placebo (1/9) patients. Clinically meaningful reductions (>50%) in ulcer area occurred in high-dose (9/13 ulcers) and low-dose (19/27) groups versus placebo (1/9; P<0.05 and P<0.005, respectively). At 12 months, significant differences were seen in TcPO2 between the high-dose and placebo groups (47.5 ± 17.8 versus 36.6 ± 24.0 mm Hg, respectively; P<0.05) and in the change from baseline among the groups (P<0.05). These data suggest that VM202 is safe and may provide therapeutic bioactivity in CLI patients.

Anti-Blood Group Antibodies in Intravenous Immunoglobulin May Complicate Interpretation of Antibody Titers in ABO-Incompatible Transplantation.

Patients receiving ABO-incompatible (ABOi) kidney transplants are treated before and after transplant with combination therapy, such as intravenous immunoglobulin (IVIG) and therapeutic plasma exchange, to prevent allograft rejection by reducing anti-A and anti-B titers. Although generally considered safe, it is well known that commercial IVIG products contain detectable anti-A and anti-B, which can be associated with hemolysis. Different preparative manufacturing techniques during the production of IVIG affect ABO antibody levels in IVIG preparations; therefore, some manufacturers now use new methods to reduce anti-A/B levels at the preproduction stage. The variations in implementing these strategies creates the potential for significant variation in antibody titers between products and, in some cases, even between lots of the same IVIG product. We report a case of persistently elevated anti-A titers in an ABOi kidney transplant recipient associated with elevated ABO antibody titers present in the preparation of IVIG used at our facility.

Cryoprecipitate AHF vs. fibrinogen concentrates for fibrinogen replacement in acquired bleeding patients - an economic evaluation.

BACKGROUND: Fibrinogen repletion in patients with acquired bleeding disorders can be accomplished by transfusing cryoprecipitate AHF (cryo) or fibrinogen concentrate (FC); thus, we undertook an economic evaluation from the transfusion service perspective regarding the use of cryo vs. FC in patients with acquired bleeding. METHODS: We created a model comparing the cost of cryo vs. FC from the transfusion service perspective. A patient with acquired bleeding requiring fibrinogen replacement could receive either 15-20 cryo units or 3-4 g FC, consistent with the guidelines from the European Task Force for Advanced Bleeding Care in Trauma. All model parameters were estimated from institutional experiences and the medical literature. Additionally, a survey of US Transfusion Medicine fellowship directors was conducted. RESULTS: After adjusting for 28% wastage and technologist salary, cryo cost is $414/5-unit pool. Depending on the dose, FC is more expensive by $976-$1303. To be competitive with cryo, FC cost must decrease by 44% or be shown to save 0·25-0·66 ICU days. Of the 30 survey replies, 96·7% of US centres do not use FC for acquired bleeding with the top three reasons being cost (30%), off-label usage (27%) and insufficient evidence for usage (20%). Only 47% are willing to pay more for FC, with $437/g as the median amount. CONCLUSION: Fibrinogen concentrate is more expensive than cryo, even after adjusting for cryo wastage. To be economically competitive with cryo, FC must cost $414/g, or save on ICU length of stay, consistent with the survey's results.

Impaired alveolarization and intra-uterine growth restriction in rats: a postnatal genome-wide analysis.

Intra-uterine growth restriction (IUGR) dramatically increases the risk of bronchopulmonary dysplasia in preterm babies, a disease characterized by arrested alveolarization and abnormal microvascular angiogenesis. We have previously described a rodent low protein diet (LPD) model of IUGR inducing impaired alveolarization, but failed to demonstrate any modification of the classical factors involved in lung development. We performed a genome-wide microarray analysis in 120 rat pups with LPD-induced IUGR and their controls, at three key time points of the alveolarization process: postnatal day 4 (P4): start of alveolarization; P10: peak of the alveolarization process and P21: end of the alveolarization process. Results were analysed using Arraymining, DAVID and KEGG software and validated by qRT-PCR and western blots. Considering a cut-off of 2:1 as significant, 67 transcripts at P4, 102 transcripts at P10 and 451 transcripts at P21 were up-regulated, and 89 transcripts at P4, 25 transcripts at P10 and 585 transcripts at P21 were down-regulated. Automatic functional classification identified three main modified pathways, 'cell adhesion molecules', 'cardiac muscle contraction' and 'peroxisome proliferator-activated receptor' (PPAR). Protein analysis confirmed involvement of the PPAR pathway, with an increase of FABP4, an activator of this pathway, at P4 and an increase of adiponectin at P21. Other data also suggest involvement of the PPAR pathway in impaired alveolarization. Our results show that deregulation of the PPAR pathway may be an important component of the mechanism inducing impaired alveolarization observed in IUGR. The complete dataset is available as GEO profiles on the Gene Expression Omnibus (GEO) database ( www.ncbi.nih.gov/geo/, GEO Accession No. GSE56956).

Vibrio cholerae O1 El Tor from southern Vietnam in 2010 was molecularly distinct from that present from 1999 to 2004.

The Vibrio cholerae O1 (VCO1) El Tor biotype appeared during the seventh cholera pandemic starting in 1961, and new variants of this biotype have been identified since the early 1990s. This pandemic has affected Vietnam, and a large outbreak was reported in southern Vietnam in 2010. Pulsed-field gel electrophoresis (PFGE) and multilocus variable-number tandem-repeat analyses (MLVA) were used to screen 34 VCO1 isolates from the southern Vietnam 2010 outbreak (23 patients, five contact persons, and six environmental isolates) to determine if it was genetically distinct from 18 isolates from outbreaks in southern Vietnam from 1999 to 2004, and two isolates from northern Vietnam (2008). Twenty-seven MLVA types and seven PFGE patterns were identified. Both analyses showed that the 2008 and 2010 isolates were distinctly clustered and separated from the 1999-2004 isolates.

Rapid detection of expanded short tandem repeats in personal genomics using hybrid sequencing.

MOTIVATION: Long expansions of short tandem repeats (STRs), i.e. DNA repeats of 2-6 nt, are associated with some genetic diseases. Cost-efficient high-throughput sequencing can quickly produce billions of short reads that would be useful for uncovering disease-associated STRs. However, enumerating STRs in short reads remains largely unexplored because of the difficulty in elucidating STRs much longer than 100 bp, the typical length of short reads. RESULTS: We propose ab initio procedures for sensing and locating long STRs promptly by using the frequency distribution of all STRs and paired-end read information. We validated the reproducibility of this method using biological replicates and used it to locate an STR associated with a brain disease (SCA31). Subsequently, we sequenced this STR site in 11 SCA31 samples using SMRT(TM) sequencing (Pacific Biosciences), determined 2.3-3.1 kb sequences at nucleotide resolution and revealed that (TGGAA)- and (TAAAATAGAA)-repeat expansions determined the instability of the repeat expansions associated with SCA31. Our method could also identify common STRs, (AAAG)- and (AAAAG)-repeat expansions, which are remarkably expanded at four positions in an SCA31 sample. This is the first proposed method for rapidly finding disease-associated long STRs in personal genomes using hybrid sequencing of short and long reads. AVAILABILITY AND IMPLEMENTATION: Our TRhist software is available at http://trhist.gi.k.u-tokyo.ac.jp/. CONTACT: moris@cb.k.u-tokyo.ac.jp SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Prescription patterns and treatment outcomes of MDR-TB patients treated within and outside the National Tuberculosis Programme in Pham Ngoc Thach hospital, Viet Nam.

OBJECTIVE: To describe and analyse the prescription patterns and treatment outcomes of MDR-TB patients managed within Green Light Committee (GLC) and outside (non-GLC) the National TB programme in Viet Nam. METHODS: Retrospective cohort study with two elements: (i) in-depth interviews and focus group discussions with clinical doctors, hospital pharmacists, and the non-GLC patients with MDR-TB; (ii) review of treatment cards and patients' charts of all GLC and non-GLC patients with MDR-TB put on treatment during 2010. RESULTS: Of 282 patients with MDR-TB, comprising 79 (28%) GLC patients MDR-TB and 203 (72%) non-GLC patients with MDR-TB, were enrolled in the study. Treatment delay was significantly higher in the GLC group (12.8 days) than the non-GLC group (2.3 days), (P = 0.004). The success rate was significantly better in GLC patients (84.8%) than in non-GLC patients (53.7%) (P < 0.001). The default rate was significantly higher in non-GLC patients than in GLC patients (25.6% vs. 6.3%), (P < 0.001). The risk of unsuccessful outcome was higher in non-GLC patients (Hazard ratio = 4.6, 95% CI: 1.8-11.8). CONCLUSIONS: The treatment outcomes of patients with MDR-TB in the GLC group were significantly better than in the non-GLC group. Reasons for the high default rate in non-GLC patients with MDR-TB must be further investigated.

Impact of haemophilia with inhibitors on caregiver burden in the United States.

Inhibitor development complicates haemophilia treatment and may impact caregiver burden. Compare overall burden of caregivers of children with/without inhibitors in the United States using a novel disease-specific questionnaire and the previously validated CarerQol. An on-line questionnaire with six burden domains (i.e. emotional stress, personal sacrifice, financial burden, medical management, child's pain, and transportation) and three visual analogue scales (VAS) was developed based upon a targeted literature review and previous survey findings. The study sample consisted of caregivers of children with haemophilia. The total burden score was calculated by summing the six individual burden domain scores. Higher scores represented greater burden. Descriptive statistics was performed to examine the sample characteristics. The Wilcoxon rank-sum test was performed to compare burden by inhibitor status. All variables were considered significant at P < 0.001. A total of 310 caregivers completed the survey; 30 of them reported caring for a child with an inhibitor. A majority of caregivers of children with inhibitors were mothers (80.0%) and between 35 and 44 years of age (56.7%). Caregivers of children with inhibitors reported significantly higher median total burden scores (99.0 vs. 76.5, P < 0.0001) and median burden-VAS scores (5.5 vs. 3.0, P < 0.0001), as compared to those caring for children without inhibitors. A similar trend was seen across all the six burden domains, with greatest difference in the median burden scores observed in the 'personal sacrifice' (3.2 vs. 2.0) and 'transportation' (3.3 vs. 2.3) domains. Burden of caregivers should be considered when assessing the psychosocial aspects of managing patients with inhibitors.

Understanding the experience of caring for children with haemophilia: cross-sectional study of caregivers in the United States.

Congenital haemophilia is an inherited bleeding disorder typically diagnosed at birth or shortly thereafter. Haemophilia imposes a significant burden on patients and their caregivers. The aim of the study was to quantify the overall burden of haemophilia on caregivers in the USA using a novel disease-specific questionnaire and the previously validated CarerQol. Targeted literature review and a previous survey conducted by the authors was used to develop an online questionnaire with six burden domains of interest to caregivers (emotional stress, financial, sacrifice, medical management, child's pain and transportation) and several visual analogue scales (VAS). Content validity of the questionnaire was confirmed by three haemophilia caregivers. The study sample consisted of caregivers of children with haemophilia identified via a previously developed opt-in research database. Descriptive statistics were employed for demographic and clinical characteristics; a generalized linear model (GLM) was used to identify factors influencing caregiver burden. A total of 310 caregivers completed the survey (45.5% response rate). Most of the participating caregivers were mothers of a child with haemophilia (88%), between 35 and 44 years of age (48%), and with a college education or a postgraduate degree (63%). 'Child's pain' was identified as the most burdensome domain to caregivers (median score = 3.50 out of 5), followed by 'emotional stress' (2.67), 'financial' (2.40), 'transportation' (2.33), 'sacrifice' (2.17) and 'medical management' (2.00) domains. Although higher income exhibited a protective effect, episodes of bleeds, current presence of an inhibitor and lower caregiver productivity in the past month negatively affected caregiver burden per GLM results. Training and educational programs should potentially be developed to address caregiver burden.

Early inhaled nitric oxide at high dose enhances rat lung development after birth.

RATIONAL: Inhaled nitric oxide (NO) is frequently administered to full term and preterm newborns in various clinical settings in order to alleviate pulmonary hypertension whilst improving oxygenation. However, the physiological effect of NO on early postnatal lung development has not yet been clearly described. We therefore investigated whether NO administered by inhalation affects lung development at early postnatal life. METHODS: Pregnant rats were placed in a chamber containing 5 ppm (iNO-5 ppm group) and 20 ppm NO (iNO-20 ppm group), started from the last day of their pregnancy in order to keep rat pups under ambient NO from birth to 7 days postnatal. Control animals were kept at room air and all rat pups were sacrificed at postnatal day 7 and day 14. RESULTS: Lung-to-body weight and wet-to-dry lung weight ratios did not significantly differ among 3 groups at postnatal day 7 and day 14. Vascular volume densities (Vv) in both NO groups (5 and 20 ppm) were higher than controls (P<0.05; P<0.001). Pulmonary vessel number was significantly increased in iNO-20 ppm group. Radial alveolar counts (RAC) and mean linear intercepts (MLI) markedly increased (consistent with increased alveolarization) in iNO-20 ppm group. This was associated with upregulation of VEGF/VEGFR-2, MT1-MMP/MMP2 and HO-1 protein expression in iNO-20 ppm group. CONCLUSIONS: We concluded that inhaled NO at 20 ppm enhanced lung development possibly through increased expression of HO-1, VEGF/VEGFR-2, and MMP2 at early stage of postnatal rat life.

Phenotypically matched vs. traditional screen method for preparing red blood cell units in patients with abnormal placentation: a decision analysis approach.

BACKGROUND: Patients with abnormal placentation are hospitalized approximately 21 days prior to scheduled delivery due to risk of peri-partum bleeding. It is required to have at least one red blood cell (RBC) unit ready throughout hospitalization. This can be accomplished by performing a type and cross (T&C) every 72 h (traditional method) or providing phenotypically matched RBC units (alternative method). METHODS: A Markov-based model was created to compare the cost-benefits between these two methods. A patient either undergoes the traditional or alternative method. If the patient already made an antibody and/or has rare phenotypes requiring frozen RBC unit at admission, then she can only enter the traditional method. All patients receive a T&C at the end of the 21st day in order to prepare RBC units for scheduled delivery. Model parameters are derived from literature and institutional experiences. RESULTS: Simulation was run for modelling of the 21-day hospitalization of each patient. The expected cost per RBC unit of the traditional method is significantly higher than the alternative method (876·59 vs. 608·32 USD, P-value <0·01). For each RBC unit, 4·85 h of technician working time is saved by the alternative method. However, to be cost-beneficial, the alternative method should be used only if the total cost of a RBC unit is <857·67 USD. CONCLUSION: Our model demonstrated that preparing phenotypically matched RBC units at admission is more cost-beneficial comparing to the traditional method of T&C every 72 h if the cost for the matched unit is <857·67 USD.

Recombinant activated factor VII in patients with acute liver failure with UNOS Status 1A: a single tertiary academic centre experience.

BACKGROUND AND OBJECTIVES: Recombinant activated factor VII (rFVIIa) is often used in off-label indications, including many situations in which the patients are at risk of thrombosis. In this study, we retrospectively reviewed the use of rFVIIa in patients with acute liver failure - UNOS Status 1A (ALF-1A) to determine its efficacy and safety profile. MATERIALS AND METHODS: Using the transplantation records, all adult patients with ALF-1A were identified from 6/2001 to 3/2009. From patients' medical charts, rFVIIa dose, blood component usage, short-term outcomes [length of intensive care unit (ICU) and hospital stay, ability to undergo orthotopic liver transplant (OLT) and in-hospital survival rate] and adverse events were examined. RESULTS: Forty-two patients with ALF-1A were identified. Fifteen patients received rFVIIa with doses ranging between 24·4 µg/kg and 126·8 µg/kg. Three patients received two doses of rFVIIa. The age, baseline activated partial thromboplastin time (aPTT) and platelet (PLT) count were not statistically different between the group receiving rFVIIa versus the group that did not. However, the prothrombin time (PT) was significantly higher in the rFVIIa group. Although the rFVIIa group stayed in the ICU longer and required significant more blood products during admission, there was no statistical difference between the two groups in terms of length of hospital stay, ability to undergo OLT and survival rate. There was no increase in complications, including thrombosis, after receiving rFVIIa. CONCLUSION: Recombinant activated factor VII (rFVIIa) appears to be safe in patients with ALF-1A, but to elucidate its full role, a randomized controlled trial would be ideal.

Bacillus thaonhiensis sp. nov., a new species, was isolated from the forest soil of Kyonggi University by using a modified culture method.

Using a new culture method for unculturable soil bacteria, we discovered a novel species, NHI-38(T), from the forest soil of Kyonggi University campus, South Korea. It was a Gram-positive, rod-shaped, and endospore-forming bacterial strain. It grew over a wide pH range (6.5-9.5), with an optimum range of pH 7-9, and in a wide range of temperatures (15-60 °C), with an optimum range of 35-45 °C. Growth was possible at 0-2 % NaCl concentration, and the optimal range was between 0.5 and 1.5 % NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that this new species clustered within the genus Bacillus; it was closely related to "Bacillus abyssalis" SCSIO 15042(T) (98.86 %), B. methanolicus NCIMB 13113(T) (95.97 %), B. vietnamensis 15-1(T) (95.8 %), B. seohaeanensis BH724(T) (95.5 %), B. timonensis MM10403188(T) (95.33 %), and B. subtilis subsp. subtilis NCIB 3610(T) (94.87 %). The main fatty acid components of this bacterium were iso-C15:0 (35.92 %), summed feature 3 (C16:1ω7c/C16:1ω6c; 16.92 %), and anteiso-C15:0 (14.19 %). The predominant quinone in this bacterial strain was MK-7. The polar lipid profile primarily comprised phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol. The genomic DNA G+C composition of the isolate was 40.7 mol%. The DNA-DNA hybridization results indicated that this strain was distinct from other Bacillus species, the degree of similarity being 50 % with "B. abyssalis", 56 % with B. methanolicus, 47 % with B. vietnamensis, 43 % with B. seohaeanensis, 46 % with B. timonensis, and 32 % with B. subtilis. Based on our results, we regard strain NHI-38(T) as a novel member of the Bacillus genus, and we propose the name Bacillus thaonhiensis (=KACC 17216(T) = KEMB 9005-019(T) = JCM 18863(T)).

Type VI Collagen Deficiency Causes Enhanced Periodontal Tissue Destruction.

The periodontal ligament (PDL) is a fibrillar connective tissue that lies between the alveolar bone and the tooth and is composed of highly specialized extracellular matrix (ECM) molecules and a heterogeneous population of cells that are responsible for collagen formation, immune response, bone formation, and chewing force sensation. Type VI collagen (COL6), a widely distributed ECM molecule, plays a critical role in the structural integrity and mechanical properties of various tissues including muscle, tendon, bone, cartilage, and skin. However, its role in the PDL remains largely unknown. Our study shows that deficiency of COL6 impairs PDL fibrillogenesis and exacerbates tissue destruction in ligature-induced periodontitis (LIP). We found that COL6-deficient mice exhibited increased bone loss and degraded PDL in LIP and that fibroblasts expressing high levels of Col6α2 are pivotal in ECM organization and cell-ECM interactions. Moreover, COL6 deficiency in the PDL led to an increased number of fibroblasts geared toward the inflammatory response. We also observed that cultured COL6-deficient fibroblasts from the PDL exhibited decreased expression of genes related to collagen fiber turnover and ECM organization as well as migration and proliferation. Our findings suggest that COL6 plays a crucial role in the PDL, influencing fibroblast function in fibrillogenesis and affecting the immune response in periodontitis. These insights advance our understanding of the molecular mechanisms underlying PDL maturation and periodontal disease.

Characteristics of depressive disorders in patients with rheumatoid arthritis and some related factors.

OBJECTIVE: Rheumatoid arthritis (RA), a type of chronic arthritis, is common in Vietnam. It has severe consequences for patients, both physically and psychologically, including depressive disorders. Therefore, early detection of depressive disorders is of high importance to help provide comprehensive treatment and improve RA patients' quality of life. This cross-sectional study explored the prevalence of depressive disorders and their salient characteristics and related factors in RA patients in Vietnam. PATIENTS AND METHODS: We enrolled 156 patients diagnosed with RA using the ACR-1987 criteria. The Patient Health Questionnaire-9 (PHQ-9) was used to screen for depressive disorders. Patients' demographic characteristics and clinical and laboratory investigation results, such as the visual analog score, complete blood count, erythrocyte sedimentation rate, Disease Activity Score 28 for RA with C-reactive protein (DAS28-CRP), and quality-of-life score (based on the SF-36 test) were analyzed. Depressive disorders assessed on the first day of admission were reevaluated by a psychiatrist if the PHQ-9 score was ≥ 5. RESULTS: According to the PHQ-9 results, depression prevalence among RA patients was 76.3%. The majority of patients (49.4%) had moderate-to-severe depression and 91% experienced sleep disorder symptoms. Negative thoughts -- suicidal ideation or self-injury - were reported by 21.8% of patients. Depression severity had a moderately positive relationship with disease activity level and a moderately negative relationship with quality of life. CONCLUSIONS: Depression prevalence was high among RA patients. Depression severity increased with disease activity and decreased quality of life.