Miracle-dz/UniFAR-FTUs huggingface dataset:
The timing of acid-induced increase in saliva secretion in transplanted submandibular glands

The purpose of this study was to determine the timing of acid-induced increase in saliva secretion and to investigate the possibility of parasympathetic reinnervation of transplanted submandibular glands (SMGs). Citric acid stimulation-induced changes in secretion of transplanted SMGs were evaluated in 27 patients who underwent SMG transplantation for keratoconjunctivitis sicca (KCS); Tc scintigraphy and Schirmer tests were done at 1, 3, 6, and 9 months after transplantation. Acetylcholinesterase staining was conducted to confirm the presence of parasympathetic reinnervation in three SMGs at 6 and 9 months after transplantation. Schirmer tests showed significantly increased secretion of the transplanted SMGs after acid stimulation at 6 and 9 months, but not at 1 and 3 months. On Tc scintigraphy, no decline was detected on the dynamic time– activity curve after acid stimulation at 1 and 3 months, but a decline was detected in nine glands at 6 months and in 19 glands at 9 months. No decline was observed in the remaining eight glands at 9 months after transplantation. The histology findings were consistent with scintigraphy results. In conclusion, acid-induced increase in saliva secretion occurs at 6 months after SMG transplantation, and parasympathetic reinnervation of the transplanted SMG might occur. 0901-5027/0801041 + 07 # 2015 International Association of Oral and Maxillofacial Surge X. J. Liu, M. Li, J. Z. Su, Z. Xie, G. Y. Yu Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China; Department of Nuclear Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Department of Global Health, Peking University School of Public Health, Beijing, China
Analysis of haematological changes in tofacitinib-treated patients with rheumatoid arthritis across phase 3 and long-term extension studies

Objectives. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. The aim of this analysis was to characterize changes in haematological parameters following tofacitinib treatment, and to compare changes in haemoglobin with markers of disease activity, fatigue and vitality. Methods. Changes in neutrophil counts, lymphocyte counts and haemoglobin levels were analysed in patients with RA from six phase 3 randomized controlled trials (n = 4271) of tofacitinib 5 or 10 mg bd, placebo or active comparators of up to 24 months’ duration, and two long-term extension (LTE) studies (n = 4858) of tofacitinib of up to 84 months’ duration. Disease activity markers included CRP and ESR. Fatigue and vitality were assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Short Form Health Survey-36 vitality domain scores. Results. In phase 3 studies, mean neutrophil and lymphocyte counts decreased and mean haemoglobin levels increased in all tofacitinib treatment groups. Haemoglobin levels and neutrophil counts stabilized in the LTE studies, while lymphocyte count decreases stabilized at approximately month 48. Increased haemoglobin was associated with decreased ESR and CRP levels. Clinically meaningful reductions in haemoglobin levels (⩾3 g/dl from baseline or haemoglobin ⩽7 g/dl) occurred in <1.0% of patients in all treatment groups. FACIT-F and Short Form Health Survey-36 vitality scores were weakly correlated with haemoglobin levels. Conclusion. Small changes in haematological parameters were seen with tofacitinib treatment, which stabilized over time in the LTE studies. Changes in haemoglobin levels, although associated with changes in ESR and CRP, were not associated with fatigue or vitality.
The effect of root canal taper on the irrigant flow: evaluation using an unsteady Computational Fluid Dynamics model.

AIM To evaluate the effect of root canal taper on irrigant flow inside a prepared root canal during final irrigation with a syringe and two types of needles, using a Computational Fluid Dynamics (CFD) model. METHODOLOGY A validated CFD model was used to simulate irrigant flow from either a side-vented or a flat 30G needle positioned inside size 30, . 02 taper, 30, . 04, 30, . 06, ProTaper F3 or size 60, . 02 taper root canals, at 3 mm short of working length (WL). Velocity, pressure and shear stress in the root canal were evaluated. RESULTS The side-vented needle could not achieve irrigant replacement to the WL in any of the cases. Significant irrigant replacement was evident further than 2 mm apically to the tip of the flat needle in the size 30, . 06 taper, F3 and size 60, . 02 taper canal. A wider distribution of wall shear stress was noted as the canal taper increased but the maximum shear stress decreased. The flat needle led to higher mean pressure at the apical foramen. Both needles showed a similar gradual decrease in apical pressure as the taper increased, but the least pressure was calculated in the size 60, . 02 taper canal. CONCLUSIONS An increase in root canal taper improved irrigant replacement and wall shear stress whilst reducing the risk for irrigant extrusion. Irrigant flow in a minimally tapered root canal with a large apical preparation size also improved irrigant replacement and wall shear stress and reduced the risk for irrigant extrusion, compared to the tapered root canals with a smaller apical preparation size.
Chronic signs of memory B cell activation in patients with Behçet’s disease are partially restored by anti-tumour necrosis factor treatment

Objectives. Behçet’s disease (BD), an auto-inflammatory vasculitis with oro-genital ulcerations, skin lesions and uveitis, is regarded as T cell mediated. A successful trial with rituximab suggests an additive role for B cells in the pathogenesis. Therefore, we studied B cell abnormalities in BD patients and the effect of TNF-blocking therapy. Methods. B cells in blood (n = 36) and tissue (n = 6) of BD patients were analysed with flow cytometry and/or immunohistochemistry and compared with healthy controls (n = 22). BD current activity form (BDCAF) in relation to B cell somatic hypermutations (SHMs) and immunoglobulin class-switching were studied. Results. Thirty-six patients (17 males) were included, mean age 44 years, average disease duration 10 years and mean BDCAF 2.7. Blood B cell numbers were significantly lower in patients than in controls (P = 0.0061), mostly due to decreased CD27+ memory B cells expressing IgM (P = 0.0001), IgG (P = 0.0002) and IgA (P = 0.0038) B cell subsets. CD27+ IgA+ B cells showed the highest magnitude of decrease in active disease, measured with BDCAF (P = 0.02). CD27+ IgM+ IgD+ B cells were impaired in replication history (P = 0.0133) and selection of SHM, whereas IgA+ B cells carried elevated SHM levels (P = 0.04) and lower IgA2 subclass usage (P = 0.0004) than controls. Immunohistochemistry revealed B cells in tissue of active mucosal ulcers. In adalimumab-treated patients, blood B cells were similar to controls. Conclusion. We show significant deviations in the memory B cell compartment, related to disease activity and therapeutic efficacy. Pronounced molecular impairments were seen in the fast-responding IgM+-memory and the mucosal IgA+-memory B cells. Because of the demonstrated abundance of B cells in affected tissue, we hypothesize relocation of memory B cells to the site of inflammation could account for the deviations found in blood of BD patients. These peripheral B cells are easily accessible as a marker to monitor therapeutic efficacy.
Apical surgery: endoscopic findings at the resection level of 168 consecutively treated roots.

AIM Endoscopic evaluation of the cut root face after root-end resection during apical surgery. METHODOLOGY Consecutive cases undergoing apical surgery from June 2006 to May 2008 were enrolled. After root-end resection, the cut root face was inspected with a rigid endoscope and the following findings were assessed: number of canals, presence of isthmus, presence and location of craze lines/cracks, frosted dentine, and gaps between root filling material and dentine. Craze lines/cracks, frosted dentine and gaps were further correlated with the age group of the patient (<45 vs. ≥ 45 years), the type of treated tooth and the presence or absence of a post/screw. RESULTS The final material included 168 resected roots. The highest frequency of isthmuses was found in mesial roots of mandibular first molars (88.5%). A craze line/crack was seen in 9.5%, frosted dentine in 79.8% and gaps in 83.3% at the cut root faces. Significant differences were observed for the location of the microfindings at the resected root surfaces (buccal vs. mesial vs. lingual vs. distal, P > 0.0001). Premolars had significantly more craze lines/cracks than anterior teeth (P = 0.006) and molars (P = 0.000). Frosted dentine was significantly more frequently seen in premolars (P = 0.027) and molars (P = 0.001) compared to anterior teeth. The age groups and the presence or absence of a post/screw did not significantly influence the findings. CONCLUSIONS Frosted dentine and gaps were frequently observed with endoscopy at the resected root surfaces. The type of tooth appeared to affect the occurrence of a craze line/crack and of frosted dentine.
Omphalocele and gastroschisis and associated malformations

The etiology of gastroschisis and omphalocele is unclear and their pathogenesis is controversial. Because previous reports have inconsistently noted the type and frequency of malformations associated with omphalocele and gastroschisis, we assessed these associated malformations ascertained between 1979 and 2003 in 334,262 consecutive births. Of the 86 patients with omphalocele, 64 (74.4%) had associated malformations. These included patients with chromosomal abnormalities (25, 29.0%); non‐chromosomal syndromes including Beckwith–Wiedemann syndrome, Goltz syndrome, Marshall–Smith syndrome, Meckel–Gruber syndrome, Oto‐palato‐digital type II syndrome, CHARGE syndrome, and fetal valproate syndrome; malformation sequences, including ectopia cordis, body stalk anomaly, exstrophy of bladder, exstrophy of cloaca, and OEIS (Omphalocele, Exstrophy of bladder, Imperforate anus, Spinal defect); malformation complexes including Pentalogy of Cantrell, and non‐syndromic multiple congenital anomalies (MCA) (26, 30.2%). Malformations of the musculoskeletal system (31, 23.5%), urogenital system (27, 20.4%), cardiovascular system (20, 15.1%), and central nervous system (12, 9.1%) were the most common other congenital malformations in patients with omphalocele and non‐syndromic MCA. Of the 60 patients with gastroschisis, 10 (16.6%) had associated malformations. In contrast to omphalocele, gastroschisis was rarely associated with a complex pattern of malformation, that is, one each (1.7%) with a chromosomal abnormality (trisomy 21), sequence (amyoplasia congenita), unspecified dwarfism, and 7 (11.7%) with MCA. We observed a striking difference in the prevalence of total malformations (74.4% vs. 16.6%, P < 0.001) and specific patterns of malformations associated with omphalocele and gastroschisis which emphasizes the need to evaluate all patients with omphalocele and gastroschisis for possible associated malformations. Malformation surveillance programs should be aware that the malformations associated with omphalocele can be often classified into a recognizable malformation syndrome or pattern (44.2%). © 2008 Wiley‐Liss, Inc.
Binding Affinity and Specificity of Neuromyelitis Optica Autoantibodies to Aquaporin-4 M1/M23 Isoforms and Orthogonal Arrays*

Autoantibodies against astrocyte water channel aquaporin-4 (AQP4) are highly specific for the neuroinflammatory disease neuromyelitis optica (NMO). We measured the binding of NMO autoantibodies to AQP4 in human astrocyte-derived U87MG cells expressing M1 and/or M23 AQP4, or M23 mutants that do not form orthogonal array of particles (OAPs). Binding affinity was quantified by two-color fluorescence ratio imaging of cells stained with NMO serum or a recombinant monoclonal NMO autoantibody (NMO-rAb), together with a C terminus anti-AQP4 antibody. NMO-rAb titrations showed binding with dissociation constants down to 44 ± 7 nm. Different NMO-rAbs and NMO patient sera showed a wide variation in NMO-IgG binding to M1 versus M23 AQP4. Differences in binding affinity rather than stoichiometry accounted for M1 versus M23 binding specificity, with consistently greater affinity of NMO-IgG binding to M23 than M1 AQP4. Binding and OAP measurements in cells expressing different M1:M23 ratios or AQP4 mutants indicated that the differential binding of NMO-IgG to M1 versus M23 was due to OAP assembly rather than to differences in the M1 versus M23 N termini. Purified Fab fragments of NMO-IgG showed similar patterns of AQP4 isoform binding, indicating that structural changes in the AQP4 epitope upon array assembly, and not bivalent cross-linking of whole IgG, result in the greater binding affinity to OAPs. Our study establishes a quantitative assay of NMO-IgG binding to AQP4 and indicates remarkable, OAP-dependent heterogeneity in NMO autoantibody binding specificity.
Nicotine drives neutrophil extracellular traps formation and accelerates collagen‐induced arthritis

Objectives. The aim was to investigate the effects of nicotine on neutrophil extracellular traps (NETs) formation in current and non‐smokers and on a murine model of RA. Methods. We compared spontaneous and phorbol 12‐myristate 13‐acetate‐induced NETosis between current and non‐smokers by DNA release binding. Nicotine‐induced NETosis from non‐smokers was assessed by DNA release binding, NET‐specific (myeloperoxidase (MPO)‐DNA complex) ELISA and real‐time fluorescence microscopy. We also used immunofluorescent staining to detect nicotinic acetylcholine receptors (nAChRs) on neutrophils and performed a functional analysis to assess the role of nAChRs in nicotine‐induced NETosis. Finally, we investigated the effects of systemic nicotine exposure on arthritis severity and NETosis in the CIA mouse model. Results. Neutrophils derived from current smokers displayed elevated levels of spontaneous and phorbol 12‐myristate 13‐acetate‐induced NETosis. Nicotine induced dose‐dependent NETosis in ex vivo neutrophils from healthy non‐smokers, and co‐incubation with ACPA‐immune complexes or TNF‐&agr; facilitated a synergistic effect on NETosis. Real‐time fluorescence microscopy revealed robust formation of NET‐like structures in nicotine‐exposed neutrophils. Immunofluorescent staining demonstrated the presence of the &agr;7 subunit of the nAChR on neutrophils. Stimulation of neutrophils with an &agr;7‐specific nAChR agonist induced NETosis, whereas pretreatment with an nAChR antagonist attenuated nicotine‐induced NETosis. Nicotine administration to mice with CIA exacerbated inflammatory arthritis, with higher plasma levels of NET‐associated MPO‐DNA complex. Conclusion. We demonstrate that nicotine is a potent inducer of NETosis, which may play an important role in accelerating arthritis in the CIA model. This study generates awareness of and the mechanisms by which nicotine‐containing products, including e‐cigarettes, may have deleterious effects on patients with RA.
Human dental pulp cell responses to new calcium silicate-based endodontic materials.

AIM To evaluate human dental pulp cell responses to radiopaque dicalcium silicate cement and white-coloured mineral trioxide aggregate (WMTA). METHODOLOGY Flow cytometry was employed to quantify the phase percentage of pulp cell cycle. Alamar Blue was used for real-time and repeated monitoring of cell proliferation. Reverse transcription-polymerase chain reaction was performed to determine gene expression in pulp cells cultured on the cements. RESULTS The cells cultured on the radiopaque dicalcium silicate cement had similar S and G2 phases in the cell cycle and proliferation to WMTA at all culture times. In addition, the two materials presented the same evolution with similar values in interleukin-1, inducible nitric oxide synthase, alkaline phosphatase, osteocalcin and bone sialoprotein gene expression at all culture times. CONCLUSIONS The dental pulp cell responses to radiopaque dicalcium silicate cement were similar to those reported for WMTA in terms of cell cycle, proliferation, immunocompatibility and osteogenic differentiation.
Health Services Use Among Veterans Using U.S. Department of Veterans Affairs and Mainstream Homeless Services

We examined the use of health and behavioral health services for two groups of homeless veterans (N = 1,302) in the New York City area who were enrolled in the U.S. Department of Veterans Affairs (VA) healthcare system—veterans who use VA homeless programs, and veterans who use mainstream homeless programs only. Using administrative records from the VA and the New York City Department of Homeless Services, we compared the characteristics of users of VA and mainstream homeless programs and examined between-group differences in VA inpatient and outpatient services use and within-group changes in services use prior and subsequent to onset of homelessness. Roughly 41 percent of veterans only used mainstream homeless services. There were no significant differences between users of VA and mainstream homeless services in terms of gender, age, ethnicity, and level of VA eligibility. Veterans who used only mainstream homeless assistance services were less likely to be engaged with—and made less intensive use of—VA health and behavioral health inpatient and outpatient services than those who used VA homeless services. Efforts should be made to identify and engage veterans who, while enrolled in VA healthcare, may go unidentified as homeless by the VA.
Effect of plunger diameter on the push-out bond values of different root filling materials.

AIMS To evaluate the effect of plunger diameter on the push-out bond strength of different root filling materials to root canal dentine. METHODOLOGY Freshly extracted human incisors (n=90) were decoronated, and the root canals were enlarged with post drills. Prepared roots were placed into a custom alignment apparatus to embed the roots vertically within self-curing acrylic resin. The specimens were randomly assigned into three groups according to the root filling system used: gutta-percha/AH Plus; Resilon/Epiphany; and fibre-reinforced composite (FRC)/Duolink resin cement. After filling, the specimens were further subdivided according to the diameter of the plunger used to employ the debonding force: 0.75, 1 and 1.25 mm. Intra-radicular bond strength was measured using the push-out test at a cross-head speed of 1 mm min(-1) . The data were analysed statistically using Kruskal-Wallis test with Bonferroni correction at P = 0.05. RESULTS Regardless of the plunger diameter, FRC yielded the highest bond strength, followed by gutta-percha and Resilon, respectively (P<0.001). In all groups, greater plunger diameter resulted in an apparent increased bond strength, but the differences were only significant in the FRC group, with the 1.25-mm plunger generating higher debonding values compared with that of its 0.75- and 1-mm versions (P<0.001). In the gutta-percha and Resilon groups, the majority of specimens had adhesive failures. Roots filled with FRC exhibited more cohesive failures than those of the other test groups. CONCLUSIONS Different plunger diameters are associated with significantly different intra-radicular push-out bond strengths of root filling systems.
Perlman syndrome: Report, prenatal findings and review

Perlman syndrome is a rare overgrowth syndrome characterized by polyhydramnios with neonatal macrosomia, nephromegaly, distinctive facial appearance, renal dysplasia, nephro‐blastomatosis, and predisposition to Wilms tumor (WT). We report on a newborn with prenatal sonographic signs of Perlman syndrome, large fetal ascites, nephromegaly and macrosomia. The clinical course was marked by neonatal distress, renal failure and refractory hypoxemia leading to death at 2 days of life. Renal histologic examination showed bilateral nephroblastomatosis. Genetic or epigenetic alterations of the 11p15 region (involved in the BWS), including mutation of the CDKN1C gene were excluded. No mutation of the GPC3 gene was identified. We review the 28 patients who have been reported with Perlman syndrome. The prognosis of Perlman syndrome is poor with a high neonatal mortality rate. Among the infants who survived beyond the neonatal period, 64% developed a WT and all had a developmental delay. Fetal macrosomia, ascites and polyhydramnios are frequent manifestations. Clinical overlaps with other overgrowth syndromes particularly Beckwith‐Wiedemann syndrome and Simpson‐Golabi‐Behmel syndrome have been emphasized. Perlman syndrome is considered as an autosomal recessive condition. We review 19 patients from seven sibships with parental consanguinity in two families only. The other cases were sporadic. The 28 reported patients had only 10 unaffected sibs. The low percentage of consanguinity among parents is also puzzling for a rare recessive condition. The molecular basis of Perlman syndrome is unknown. (Epi)genetic anomalies of 11p15 and mutations in GPC3 were not studied in most of the previous reports. © 2008 Wiley‐Liss, Inc.
Metabolic Syndrome and its components among Qatari population

Metabolic Syndrome (MeS) is a cluster of abnormalities including impaired glucose metabolism, central obesity, dyslipidemia and hypertension. The MeS has not been widely studied among the Arab populations, but the data available suggests that it is an increasingly common problem. Prevalence of MeS and its associated components are not available in Qatar. To estimate the prevalence of MeS and its associated components among the Qatari population and to determine its associated risk factors, a cross-sectional study was carried out among Qatari adults aged 20 years and above. Face to face interviewing using a structured questionnaire followed by laboratory tests were conducted. MeS was defined using the Adult Treatment Panel III (ATP III) criteria as well as the International Diabetes Federation criteria (IDF). The crude prevalence rate of MeS according to ATP III criteria and IDF criteria were 26.4 and 34.0%, respectively. The age-standardised prevalence of the MeS according to ATP III was 27.7% (95% CI 23.3? 32.0%), (23.6% among men (95% CI 19.5? 27.7%) and 32.6% among women (95% CI 28.0? 37.2%)) and according to IDF criteria, the age standardised prevalence was 35.4% (95% CI 30.7? 40.0%), 38.7% (95% CI 34.0? 43.5%) for women and 35.8% (95% CI 31.2? 40.5%) for men. Age, Body Mass Index and HbA1c were significantly associated with MeS after adjustment for a number relevant variables including; gender, marital status, educational level, exercise, smoking, etc. Prevalence of the MeS in Qatar is considerably higher than anticipated. A well-designed health education programmes to increase the awareness of the public as well as healthcare providers are highly recommended. The programme should focus on the risk factors and the health consequences of MeS.