Non-Infectious Complications in B-Lymphopenic Common Variable Immunodeficiency.

BACKGROUND AND OBJECTIVE: Common variable immunodeficiency (CVID) is considered the most symptomatic type of inborn errors of immunity in humans. Along with infectious complications, which have numerous consequences, non-infectious complications are also a major challenge among CVID patients. METHODS: All registered CVID patients in the national database were included in this retrospective cohort study. Patients were divided into two groups based on the presence of B-cell lymphopenia. Demographic characteristics, laboratory findings, non-infectious organ involvements, autoimmunity, and lymphoproliferative diseases were evaluated. RESULTS: Among 387 enrolled patients, 66.4% were diagnosed with non-infectious complications; however, 33.6% had only infectious presentations. Enteropathy, autoimmunity, and lymphoproliferative disorders were reported in 35.1%, 24.3%, and 21.4% of patients, respectively. Some complications, including autoimmunity and hepatosplenomegaly, were reported to be significantly higher among patients with B-cell lymphopenia. Among organ involvement, dermatologic, endocrine and musculoskeletal systems were predominantly affected in CVID patients with B-cell lymphopenia. Among autoimmune manifestations, the frequency of rheumatologic, hematologic, and gastrointestinal autoimmunity was reported to be higher compared to other types of autoimmunity independent from the B cell-lymphopenia. Furthermore, hematological cancers, particularly lymphoma, were slightly introduced as the most common type of malignancy. Meanwhile, the mortality rate was 24.5%, and respiratory failure and malignancies were reported as the most common cause of death in our patients without significant differences between the two groups. CONCLUSION: Considering that some of the non-infectious complications might be associated with B-cell lymphopenia, therefore, regular patient monitoring and follow-up along with proper medications (besides immunoglobulins replacement therapy) are highly recommended to prevent further sequels and increase the patients' quality of life.

The associations between bone mineral density with body composition parameters in postmenopausal women.

Body composition plays an essential role in bone health among postmenopausal women thus we decided to compare body composition in normal bone mass density, osteopenia and osteoporosis women. In this cross-sectional study, 142 normal, 109 osteoporotic, and 194 osteopenic postmenopausal women were selected. Socio-demographic and anthropometric characteristics were investigated. IPAQ-SF questionnaire was applied for evaluating physical activity. Body composition data were obtained using the bioimpedance analysis (BIA) method. A logistic regression model adjusted for confounders was used to estimate the risk of osteopenia and osteoporosis. The odds of osteopenia decreased by increasing Percent Body Fat, PBF (aOR: 0,922; 95% CI 0,867-0,980), Mass of Body Fat, MBF (aOR: 0,909; 95% CI: 0,872 to 0,947), Soft Lean Mass, SLM (aOR: 0,921; 95% CI 0,880-0,964), Lean Body Mass, LBM (aOR: 0,910; 95% CI 0,871-0,951), Visceral Total Body Water, TBW (aOR: 0,878; 95% CI 0,828-0,933), mineral mass (aOR: 0,356; 95% CI 0,231-0,548), body weight (aOR: 0,955; 95% CI 0,934-0,976), and Body Mass Index, BMI (aOR: 0,896; 95% CI 0,848-0,947). The odds of osteoporosis decreased by increasing PBF (aOR: 0,838; 95% CI 0,773-0,909), MBF (aOR: 0,840; 95% CI 0,792-0,891), SLM (aOR: 0,889; 95% CI 0,839-0,941), LBM (aOR: 0,910; 95% CI 0,871-0,951), Visceral Fat Mass, VFM (aOR: 0,465; 95% CI 0,351-0,615), mineral mass (aOR: 0,163; 95% CI 0,086-0,307), body weight (aOR: 0,907; 95% CI 0,876-0,938), and BMI (aOR: 0,797; 95% CI 0,733-0,867). Increased body composition parameters reduced the risk of low bone mass density.

Propagation of registration uncertainty during multi-fraction cervical cancer brachytherapy.

Multi-fraction cervical cancer brachytherapy is a form of image-guided radiotherapy that heavily relies on 3D imaging during treatment planning, delivery, and quality control. In this context, deformable image registration can increase the accuracy of dosimetric evaluations, provided that one can account for the uncertainties associated with the registration process. To enable such capability, we propose a mathematical framework that first estimates the registration uncertainty and subsequently propagates the effects of the computed uncertainties from the registration stage through to the visualizations, organ segmentations, and dosimetric evaluations. To ensure the practicality of our proposed framework in real world image-guided radiotherapy contexts, we implemented our technique via a computationally efficient and generalizable algorithm that is compatible with existing deformable image registration software. In our clinical context of fractionated cervical cancer brachytherapy, we perform a retrospective analysis on 37 patients and present evidence that our proposed methodology for computing and propagating registration uncertainties may be beneficial during therapy planning and quality control. Specifically, we quantify and visualize the influence of registration uncertainty on dosimetric analysis during the computation of the total accumulated radiation dose on the bladder wall. We further show how registration uncertainty may be leveraged into enhanced visualizations that depict the quality of the registration and highlight potential deviations from the treatment plan prior to the delivery of radiation treatment. Finally, we show that we can improve the transfer of delineated volumetric organ segmentation labels from one fraction to the next by encoding the computed registration uncertainties into the segmentation labels.

Elevated levels of IL-2 and IL-21 produced by CD4+ T cells in inflammatory bowel disease.

CD4+ T cells are considered as a subset of cells that play a pivotal role in the development of inflammatory bowel disease (IBD). The aim of this study was to assess the levels of interleukin (IL)-2, IL-21 and their receptors produced by CD4+ T cells in patients with inflammatory bowel disease. Thirty-two patients with ulcerative colitis (UC) and mean age of 37.93±10.37 years, as well as 22 patients with Crohn’s disease (CD) and mean age of 37.04±10.44 years, were studied. The healthy controls (HC) included 31 subjects with a mean age of 36.7±10.48 years. Peripheral blood mononuclear cells (PBMCs) were isolated from all the participants. The CD4+ T cells were isolated and the expression of IL-2 and IL-21 and also their receptors were examined by flow cytometry. The level of IL-2+ cells was significantly increased in UC patients compared with HC (40.71±6.04 vs 37.24±6.54, respectively, p=0.04). The level of IL-21+ cells was also significantly elevated in CD patients compared with HC (4.44±1 vs 3.83±0.74, respectively, p=0.02). Furthermore, we found a significant positive correlation between clinical activity index (CAI) and IL-21+ cells. According to the results, we hypothesize that the elevated level of IL-2+ and IL-21+ T cells and a positive correlation between IL-21+ cells with CAI in UC patients may contribute to the pathogenesis of disease. Moreover, the assessment of cells producing such cytokines constitutes a potential diagnostic and therapeutic strategy for IBD.

Evaluation of tolerance in patients with type-1 hypersensitivity reaction to wheat after oral immunotherapy

No disponible

Induction of tolerance by oral immunotherapy in patients with cow's milk allergy

No disponible

The effects of aqueous extract of vaccinium arctostaphylos leaves on blood pressure in renal hypertensive rats.

BACKGROUND: The leaves of Vaccinium arctostaphylos (Qare qat) is advocated for the treatment of hypertension in Iran' folk medicine. The objective of was to examine the possible hypotensive activity of aqueous extract of Vaccinium arctostaphylos leaves in rat model of two-kidney, one-clip hypertension. METHODS: Rats were subjected to sham operation of the placement of Plexiglass clip on left renal arteries. Four weeks later, renal artery clipped rats were given intravenous injection of normal saline or the extract at 10, 25, or 75 mg/kg, and mean blood pressure and heart rate were measured before and 20, 40 and 60 minutes after vehicle or drug administration. RESULTS: Compared to sham group, renal artery clipped groups had a significantly higher mean blood pressure, heart and right kidney weights, lower left kidney weight and significantly indifferent heart rate. Compared to vehicle treatment, the extract at 75 mg/kg, but not at 10 or 25 mg/kg, did reduce the mean blood pressure at 20, 40 and 60 minutes after administration without changing the heart rate. CONCLUSION: The findings showed that at a higher dose the extract did have hypotensive activity without changing the heart rate. The exact hypotensive mechanism remains to be investigated.

The investigation of allele and genotype frequencies of CYP3A5 (1/3) and P2Y12 (T744C) in Iran.

Research on the frequency of the highly functional mutations of genes coding required for metabolizing enzymes has shown significant ethnic variations. However, few studies, if any, have examined the frequency distribution of major allelic variations in the context of Iran. In this regard, the present study focused on the genotype profile of Southern Iranians in order to compare allele frequencies of their CYP3A5 and P2Y12 (T744C) which have been shown to have roles in metabolizing clopidogrel, with those of other populations. Therefore, genotyping was carried out on 112 unrelated individuals by PCR-RFLP. The CYP3A5*3 allele was found in 185 persons with allelic frequency 0.82, which is the most common allele among Caucasians (90-95%). The frequency of 82% is different from other Caucasians (90-94%), Indians (67%), Vietnam (67%) and Africans (15%). but lower than frequency in Chinese populations (74%) and Korean (76%). The allele frequency of the -744T (4%) is different from frequencies of Caucasian, American, Chinese, Korean, and Subsahara population. This study confirmed significant inter-ethnic differences in CYP3A5 and P2Y12 frequencies between Iranians and other ethnic groups. The results of this study will be useful for clinical pharmacokinetic investigations and drug dosage recommendations especially antiplatelet drugs such as Clopidogrel, for Iranians.

The effect of post-exercise carbohydrate ingestion on inflammatory responses to short time, high-force eccentric exercise.

AIM: The aim of this study was to investigate muscle damage and inflammatory response following eccentric exercise as well as the effect of carbohydrate supplement on these responses in untrained men. METHODS: Eighteen healthy untrained men were randomly allocated into two carbohydrate (age 21/33+/-0/7 years) and placebo (age 20/66+/-1/22 years) groups. Forty-five repetitions of eccentric elbow flexion were performed with 90% of one maximum repetition by each subject. The exercises were done as three sets of 15 repetitions with 3 minutes rest between sets. Venous blood samples were obtained at pre-exercise, immediately, 8h, and 24h after exercise. Subjects consumed a 6% carbohydrate or placebo drink immediately following the exercise session, every hour, for 10 hours. RESULTS: CK activities and IL-6 levels were significantly greater than per-exercise in immediately, 8 h and 24 h after exercise in both groups (P<0.05). No significant increases was observed in CRP levels immediately, 8 h and 24 h after exercise versus baseline, in both groups (P>0.05), but in 8 h versus immediately after exercise, the augmentation in the carbohydrate group was significant(P<0.05). Blood glucose increased significantly 8 h after exercise versus baseline in both groups (P<0.05). There was significant difference in serum IL-6 between two groups in 8 h and 24 h after exercise (P<0.05) and it was greater in carbohydrate group. There was no significant difference in serum CK, CRP, and glucose between two groups (P>0.05). CONCLUSION: According to results, carbohydrate increased the inflammatory (IL-6) response following resistance exercise, but had no effects on CRP and CK.

Dissociative recombination of water cluster ions with free electrons: cross sections and branching ratios.

Dissociative recombination (DR) of water cluster ions H(+)(H(2)O)(n) (n=4-6) with free electrons has been studied at the heavy-ion storage ring CRYRING (Manne Siegbahn Laboratory, Stockholm University). For the first time, branching ratios have been determined for the dominating product channels and absolute DR cross sections have been measured in the energy range from 0.001 to 0.7 eV. Dissociative recombination is concluded to result in extensive fragmentation for all three cluster ions, and a maximum number of heavy oxygen-containing fragments is produced with a probability close to unity. The branching ratio results agree with earlier DR studies of smaller water cluster ions where the channel nH(2)O+H has been observed to dominate and where energy transfer to internal degrees of freedom has been concluded to be highly efficient. The absolute DR cross sections for H(+)(H(2)O)(n) (n=4-6) decrease monotonically with increasing energy with an energy dependence close to E(-1) in the lower part of the energy range and a faster falloff at higher energies, in agreement with the behavior of other studied heavy ions. The cross section data have been used to calculate DR rate coefficients in the temperature range of 10-2000 K. The results from storage ring experiments with water cluster ions are concluded to partly confirm the earlier results from afterglow experiments. The DR rate coefficients for H(+)(H(2)O)(n) (n=1-6) are in general somewhat lower than reported from afterglow experiments. The rate coefficient tends to increase with increasing cluster size, but not in the monotonic way that has been reported from afterglow experiments. The needs for further experimental studies and for theoretical models that can be used to predict the DR rate of polyatomic ions are discussed.

Impact of rapid molecular screening for meticillin-resistant Staphylococcus aureus in surgical wards.

BACKGROUND: This study aimed to establish the feasibility and cost-effectiveness of rapid molecular screening for hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA) in surgical patients within a teaching hospital. METHODS: In 2006, nasal swabs were obtained before surgery from all patients undergoing elective and emergency procedures, and screened for MRSA using a rapid molecular technique. MRSA-positive patients were started on suppression therapy of mupirocin nasal ointment (2 per cent) and undiluted chlorhexidine gluconate bodywash. RESULTS: A total of 18,810 samples were processed, of which 850 (4.5 per cent) were MRSA positive. In comparison to the annual mean for the preceding 6 years, MRSA bacteraemia fell by 38.5 per cent (P < 0.001), and MRSA wound isolates fell by 12.7 per cent (P = 0.031). The reduction in MRSA bacteraemia and wound infection was equivalent to a saving of 3.78 beds per year (276,220 pounds sterling), compared with the annual mean for the preceding 6 years. The cost of screening was 302,500 pounds sterling, making a net loss of 26,280 pounds sterling. Compared with 2005, however, there was a net saving of 545,486 pounds sterling. CONCLUSION: Rapid MRSA screening of all surgical admissions resulted in a significant reduction in staphylococcal bacteraemia during the screening period, although a causal link cannot be established.

Dissociative recombination of H+(H2O)3 and D+(D2O)3 water cluster ions with electrons: cross sections and branching ratios.

Dissociative recombination (DR) of the water cluster ions H(+)(H(2)O)(3) and D(+)(D(2)O)(3) with electrons has been studied at the heavy-ion storage ring CRYRING (Manne Siegbahn Laboratory, Stockholm University). For the first time, absolute DR cross sections have been measured for H(+)(H(2)O)(3) in the energy range of 0.001-0.8 eV, and relative cross sections have been measured for D(+)(D(2)O)(3) in the energy range of 0.001-1.0 eV. The DR cross sections for H(+)(H(2)O)(3) are larger than previously observed for H(+)(H(2)O)(n) (n=1,2), which is in agreement with the previously observed trend indicating that the DR rate coefficient increases with size of the water cluster ion. Branching ratios have been determined for the dominating product channels. Dissociative recombination of H(+)(H(2)O)(3) mainly results in the formation of 3H(2)O+H (probability of 0.95+/-0.05) and with a possible minor channel resulting in 2H(2)O+OH+H(2) (0.05+/-0.05). The dominating channels for DR of D(+)(D(2)O)(3) are 3D(2)O+D (0.88+/-0.03) and 2D(2)O+OD+D(2) (0.09+/-0.02). The branching ratios are comparable to earlier DR results for H(+)(H(2)O)(2) and D(+)(D(2)O)(2), which gave 2X(2)O+X (X=H,D) with a probability of over 0.9.

Rotational state effects in the dissociative recombination of H2+.

We have studied the dissociative recombination (DR) of molecular hydrogen ions with slow electrons over a range of collision energies from 0 to 400 meV. By employing a pulsed expansion source for rotational cooling and by exploiting super elastic collisions with near-0-eV electrons in a heavy ion storage ring for vibrational cooling, we observe a highly structured DR cross section, comparable to that reported for HD+. Using para-hydrogen-enriched ion beams, we identify for the first time features in the DR cross sections attributed to nu=0, J=even molecules (para-H2) and nu=0, J=odd (ortho-H2) molecules, separately. Indications are given that para levels have different DR rate coefficients from ortho levels for the first four vibrational levels at near-0-eV collisions.

Dynamic regimes of buoyancy-affected two-phase flow in unconsolidated porous media.

The invasion and subsequent flow of a nonwetting fluid (NWF) in a three-dimensional, unconsolidated porous medium saturated with a wetting fluid of higher density and viscosity have been studied experimentally using a light-transmission technique. Distinct dynamic regimes have been found for different relative magnitudes of viscous, capillary, and gravity forces. It is shown that the ratio of viscous and hydrostatic pressure gradients can be used as a relevant dimensionless number K for the characterization of the different flow regimes. For low values of K, the invasion is characterized by the migration and fragmentation of isolated clusters of the NWF resulting from the prevalence of gravity and capillary forces. At high values of K, the dominance of viscous and gravity forces leads to an anisotropic fingerlike invasion. When the invasion stops after the breakthrough of the NWF at the open upper boundary, the invasion structure retracts under the influence of gravity and transforms into stable vertical channels. It is shown that the stability of these channels is the result of a balance between hydrostatic and viscous pressure gradients.

Urethral reconstruction using autologous and everted vein graft: an experimental study.

Urethral reconstruction is one of the problematic issues in pediatric surgery. To evaluate the efficacy of vein graft for urethral reconstruction in rabbits, about 3 cm of distal urethra was excised under microscopic magnification. In groups A, B, and D, the urethra was replaced with the internal jugular vein. In group B, before performing anastomosis, vein grafts were everted. In group C (control group) after removing the urethra, a catheter was inserted without substituting the urethra and then fixed. Groups A, B, and C were kept for 3 months. Group D was divided into five subgroups each consists of two rabbits, which were killed at days 7, 10, 14, 22, and 30 for evolutionary histopathological studies. Gross evaluation, retrograde urethrography, and histopathological studies were also performed in other groups. Retrograde urethrography and gross evaluation revealed no sign of stricture and fistula formation in six and eight rabbits in groups A and B, respectively. However, those complications were observed in all the rabbits in group C. The grafted part of the neourethra was epithelialized with uroepithelium in all rabbits in group A (vein graft) and group B (everted vein graft) but only partial epithelialization was observed in three rabbits of group C. Severe fibrosis with stricture formation was developed in six rabbits in the control group. In group D, epithelialization gradually replaced necrosis and inflammation, within 1 month. This study showed that vein, everted or not, can be used as a substitute for urethra. It also suggests that new epithelialization might be formed from ingrowing of the uroepithelium from the proximal part.

Chronological and ultrastructural changes in camel (Camelus dromedarius) oocytes during in vitro maturation.

Cumulus-oocyte complexes (COCs) were collected from non-pregnant camels at a local slaughterhouse by aspiration from antral follicles (2-6 mm). In Experiment I, camel COCs (n=304) were matured in vitro in Hams-F10, fixed at different time intervals (6, 12, 18, 24, 30, 36, 42, or 48 h) and stained with 1% aceto-orcein to assess nuclear changes in culture. A majority of the oocytes (81.5%) underwent germinal vesicle break down (GVBD) between 6 and 12h. Forty-eight percent of the oocytes were observed at the metaphase I (M I) stage by 18 h culture. The percentage of matured oocytes (M II stage) at 30 and 42 h were 66.5 and 71% respectively, which were significantly (p<0.05) different to that observed at 24 h (42.5%). In Experiment II, after different periods of culture (12, 24, 36, or 48 h), the COCs (n=26) were processed for transmission electron microscopy. Expansion of both the cumulus and corona radiate cells occurred between 12 and 24 h in the majority of oocytes concomitant with enlargement of the cumulus cell process endings (CCPEs) in the developed perivitelline space. After 12 h of culture disruption of the junctions between CCPEs and the oolemma was observed together with and breakdown of the GV. For 24-36 h of culture cortical granules had spread and aligned along the oolemma. Signs of degeneration in the cytoplasmic organelles of the oocytes were also observed from less than 36 h. After 48 h of culture, larger vesicles and lipid droplets had appeared in the central part of the oocytes and showed uneven distribution throughout the ooplasm. Predominantly non-penetrating CCPEs were also observed in four oocytes by 48 h. In conclusion, based on both light and electron microscopic evaluations, the optimal culture time for the development of competent Camelus dromedarius oocytes in vitro appears to be 30 h using Hams-F10 medium.

Dissociative recombination cross section and branching ratios of protonated dimethyl disulfide and N-methylacetamide.

Dimethyl disulfide (DMDS) and N-methylacetamide are two first choice model systems that represent the disulfide bridge bonding and the peptide bonding in proteins. These molecules are therefore suitable for investigation of the mechanisms involved when proteins fragment under electron capture dissociation (ECD). The dissociative recombination cross sections for both protonated DMDS and protonated N-methylacetamide were determined at electron energies ranging from 0.001 to 0.3 eV. Also, the branching ratios at 0 eV center-of-mass collision energy were determined. The present results give support for the indirect mechanism of ECD, where free hydrogen atoms produced in the initial fragmentation step induce further decomposition. We suggest that both indirect and direct dissociations play a role in ECD.