Incidence and genetic risk of juvenile idiopathic arthritis in Norway by latitude.

OBJECTIVES: We aimed to investigate the incidence of juvenile idiopathic arthritis (JIA) in the three geographical regions of Norway, and whether potential regional incidence differences are explained by environmental or genetic factors across regions. METHODS: We conducted a register-based cohort study including all Norwegian children born 2004-2019, with follow-up throughout 2020. The JIA diagnosis defined by ≥ 2 ICD-10 codes for JIA was validated against medical records. The incidence rate (IR) and hazard ratio (HR) for JIA were estimated for all Norway, and for the regions North, Mid, and South. In a sub-sample from the Norwegian Mother, Father, and Child Cohort Study (MoBa), the genetic risk for JIA was assessed in the three regions. RESULTS: After median 9.1 (range 0.3-16.0) years of follow-up, we identified 1184 JIA cases and 910058 controls. The IR for JIA/100 000 person-years was 14.4 in all of Norway; 25.9 in region North, 17.9 in region Mid and 12.5 in region South. The HR (95% CI) of JIA in region North was 2.07 (1.77-2.43) and in region Mid 1.43 (1.23-1.67) compared to region South. Adjustments for perinatal factors, socioeconomic status, and early antibiotic exposure did not change our estimates substantially. In MoBa (238 cases, 57392 controls), the association between JIA and region of birth was no longer significant when adjusting for genetic factors. CONCLUSIONS: We found a higher incidence of JIA with increasing latitude, without evidence for available environmental factors explaining the observed gradient. In contrast, genetic factors modified the association, but further studies are warranted.

Harnessing the therapeutic potential of bone marrow-derived stem cells for sciatic nerve regeneration in diabetic neuropathy.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes that affects the angiogenesis and myelination of peripheral nerves. In this study, we investigated the potential of mesenchymal stem cells (MSCs) transplantation to improve DPN by enhancing angiogenesis and remyelination in the sciatic nerve of streptozotocin (STZ)-induced diabetic female rats. The purpose of this study was to evaluate the therapeutic potential of mesenchymal stem cells as a possiblity for clinical intervention to alleviate the symptoms of diabetic peripheral neuropathy. We examined whether transplanted mesenchymal stem cells can produce new and restored angiogenesis, as well as promoting myelination. Overall, our findings suggest that MSCs transplantation has neuroprotective effects. This is particularly the case for Schwann cells. Transplantation may stimulate angiogenesis as well as remyelination of the sciatic nerve in experimentally-induced diabetic peripheral neuropathy. Behavioral assays, histological analysis, and molecular techniques were used to assess the effects of MSCs transplantation. Our results demonstrate that in diabetic rats signs of neuropathy were reversed following a single administration of bone marrow-derived MSCs. Morphological and morphometric analysis of the sciatic nerve revealed that diabetic rats displayed structural alterations that were attenuated with MSCs transplantation.Immunostaining analysis showed increased expression of S100 and VEGF in the sciatic nerve following MSCs transplantation. Western blotting analysis also revealed elevated levels of VEGF and CD31 in rats treated with MSCs compared to diabetic rats.

Molecular and immunohistochemical study of APC exon 16 and its possible role in colorectal carcinoma development.

Background: Colorectal cancer ranks second as a cause of cancer deaths. Mutations in the adenomatous polyposis coli (APC) gene, especially in exon 16, could contribute to colorectal carcinoma development. This study explored the correlations between APC gene exon 16 variations/expression and colorectal carcinoma progression. Methods: In a case-control study, blood samples from 150 colorectal carcinoma patients and 50 healthy volunteers were analyzed by PCR and sequencing for APC exon 16 variations. The APC protein expression on tissue samples was evaluated by immunohistochemistry and statistical analyses were used to examine clinicopathological correlations. Results: The sequencing analysis revealed a mutation in exon 16 of the APC gene (rs459552) in 36 % of colorectal cancer cases while absent in all non-cancer controls. Subgroup analysis by tumor grade showed higher prevalence of mutant allele in Grade II and Grade III cases, with frequencies reaching 60.0 % and 69.2 %, respectively, compared to a substantially lower prevalence of 29.4 % in Grade I patients. Immunohistochemistry showed no significant correlation between this mutation and APC expression. APC positivity proportions were 25.5 % in Grade I tumors (n = 26/102) versus 17.1 % in Grade II (n = 6/35) and 46.2 % in Grade III (n = 6/13), showing a non-significant trend of reduced positivity in higher grade tumors (p>0.05). Conclusions: The frequency of APC exon 16 mutation (rs459552) rose significantly with increasing tumor grade. Similarly, although not statistically significant, the percentage of APC positive staining increased with poorer tumor differentiation, rather than declining. Therefore, the APC exon 16 mutation and expression analysis provides insights into colorectal cancer progression, with the rs459552 mutation correlating with grade and may promoting aggression.

Identification and mapping of brain natriuretic peptide in the normal ventricular myocardium of a desert-dwelling mammalian model, the camel (Camelus dromedarius): Immunohistochemical and ultrastructural study.

Brain natriuretic peptide (BNP) is mainly produced in the ventricular myocardium, where it is released into the circulation, producing rapid volume decrease by diuresis, natriuresis, and water shift into the extracellular space, and vasodilation. The dromedary camel, a mammalian model of the desert nomads, lives under unfavorable physiological stresses during thirst, starvation, desiccation, and hot climate, thus has a special demand for water homeostasis. The present studies characterized BNP in the ventricular myocardium of healthy camels, immunohistochemically with a specific antibody, and ultrastructurally identified the endocrine property of the cardiomyocytes and Purkinje fibers. The paranuclear, granular, immunoreactive material was not restricted to the cardiomyocytes, as it was also visible in the Purkinje fibers and their associated nerve varicosities. The intensity of immunoreactive BNP showed a transmural gradient from the subepicardium to the myocardium. Intense immunoreactivity was also noted among the perivascular cardiomyocytes. At the electron microscopic level, specific granules were demonstrated in the paranuclear cytosol of cardiomyocytes and Purkinje fibers. The current study provides the first immunohistochemical localization pattern of BNP in the camel myocardium and suggests a relationship between the intense subepicardial BNP-immunoexpression and a possible translocation of the active hormone to the pericardial fluid for further paracrine actions on the heart and its coronaries.

Survey of nuclear progesterone receptor expression in the uterus of the cyclic and pregnant camel (Camelus dromedarius).

Progesterone receptors (PR) are necessary to mediate the biological effects of progesterone and are integral to the regulation of a number of different aspects of reproduction in mammals including ovulation of the oocyte, implantation of the conceptus and maintenance of pregnancy. This study investigated the expression and localization of progesterone receptors in the uterine wall of both pregnant and cyclic (nonpregnant) camels. Uterine tissue samples were collected from healthy animals and processed for routine histological and immunohistochemical staining techniques to reveal nuclear PR. Demonstration of PR was performed by indirect immunohistochemical techniques using monoclonal antibodies raised against human PR. Immunolocalization of PR was more intense in all four endometrial zones (I-IV) as well as the myometrium of non pregnant (cyclic) animals (animals with newly formed corpus luteum). In contrast, PR immunostaining in both the endometrium and the myometrium was greatly reduced in pregnancy, particularly in the latest stage examined (approximately 366 days of gestation). In conclusion, a better understanding of the expression of steroid hormones and their receptors, including progesterone and the PR is critical to improving the reproductive health and pregnancy in the domesticated dromedary camel.

Autophagy in normal tissues of camel (Camelus dromedarius) with focus on immunoexpression of LC3 and LC3B.

Autophagy is a highly regulated intracellular pathway for degradation and recycling of cytoplasmic protein aggregates and entire organelles. The autophagic pathway is stimulated by nutrient starvation, which prompted us to study the desert camel. Various organs of the camel undergo ecological and physiological stress due to food and water deprivation, dehydration and long exposure to solar radiation. We investigated the immunohistochemical expression of specific biomarkers of autophagy under normal conditions as a baseline for later work on stressed individuals. The autophagy-specific biomarkers, microtubule-associated protein1 light chain 3 (LC3), and its cleaved variant, LC3B, were strongly expressed in the cytosol of all tissues examined. The cytosolic immunoreactivity of LC3 was relatively weak, diffuse and vacuolar, while that of LC3B was stronger, punctate and at lower levels. LC3 appears to be associated with the autophagosomal membranes, either free or lysosome-bounded. LC3B is specific for the autophagosome-lysosome complexes and their degraded, granular contents. Autophagy was strongly expressed in CNS neurons and intestinal neural elements, which suggests a protective function for the nervous system. Autophagic markers also were seen in deformed immune-competent cells with fragmented nuclei in lymph nodes, spleen and gut-associated lymphoid tissue (GALT), which suggests a "suicidal" activity of eliminating unneeded cells. Autophagy, as measured by LC3 and LC3B expression, may participate in a general regulatory mechanism in tissues of the desert camel.

Immunohistochemical expression of apoptosis-related biomarkers in normal tissues of camel (Camelus dromedarius): A survey in a desert-dwelling mammalian model.

Programmed cell death is a fundamental event that takes place during organ development and plays an important role in cellular homeostasis. Since various body organs of the camel are under high ecological and physiological stress during food and water deprivation, desiccation, and the long exposure to solar radiation in these desert nomads, we aimed to examine the immunohistochemical expression of apoptosis-related biomarkers in some of its normal body organs to illustrate a basic track for further pathological investigation. Regarding apoptosis, the present study has revealed that the higher expression of cleaved caspase-9 (CC9) [initiator of the intrinsic pathway] and CC3 (effector caspase), and the scanty expression of CC8 (initiator of the extrinsic pathway), highlight the role of the caspase-dependent, intrinsic apoptotic pathway particularly in the intestines and lymphoid organs. The apoptosis- inducing factor (AIF)-immunoexpression was completely missing in the cell nuclei of the examined tissues, indicating the absence of the caspase-independent pathway. The nuclear overexpression of the phospho-histone H2AX (γ H2AX) and the occasional expression of single-stranded DNA, particularly among the CNS neurons, suggest an efficient, protective DNA-repair mechanism in such cells. Thus, despite efficient anti-apoptotic mechanisms intrinsic apoptotic pathways exists in brain, intestine and lymph organs of adult desert camels.

Sixth Drag Prediction Workshop Results Using FUN3D with k-kL-MEAH2015 Turbulence Model.

The Common Research Model wing/body configuration is investigated with the k-kL-MEAH2015 turbulence model implemented in FUN3D. This includes results presented at the Sixth Drag Prediction Workshop and additional results generated after the workshop with a nonlinear quadratic constitutive relation variant of the same turbulence model. The workshop-provided grids are used, and a uniform grid refinement study is performed at the design condition. A large variation between results with and without a reconstruction limiter is exhibited on "medium" grid sizes, indicating that the medium grid size is too coarse for drawing conclusions in comparison with experiment. This variation is reduced with grid refinement. At a fixed angle of attack near design conditions, the quadratic constitutive relation variant yielded decreased lift and drag compared with the linear eddy-viscosity model by an amount that was approximately constant with grid refinement. The k-kL-MEAH2015 turbulence model produced wing-root junction flow behavior consistent with wind-tunnel observations.

Superior angiogenesis facilitates digit regrowth in MRL/MpJ mice compared to C57BL/6 mice.

Previous studies indicated that the fast-healer strain of MRL/MpJ-Fas(lpr)/J (MRL) mice demonstrated superior regenerative capabilities for digit wound healing and/or regeneration compared with the non-healer strain of C57BL/6 (C57) mice. These reports, however, mainly focused on morphological observations and analysis of gene expression with little attention on the role of angiogenesis in the amputated digits. By taking advantage of Laser Doppler Imaging and histological analysis, we examined the potential role(s) of angiogenesis in facilitating tissue regrowth/regeneration by comparing two strains of mice (MRL versus C57). The three middle digits on the mouse's right foot (RF) were amputated at the middle level of phalanx 2 (P2) on postnatal day 2 (Day 0), while the left foot (LF) remained intact and served as a control. Laser Doppler images and digital photographs were taken of both feet before, immediately after surgery, and on Day 7, 14, 21, and 28 to evaluate blood flow and overall length of digit regrowth. All measurements from the amputated digits of the RF were divided by those of the control LF to obtain normalized ratios for statistical comparisons between groups. It was found that MRL mice demonstrated an approximately 220% increase in regrowth ratios over that of C57 mice from Day 21-28 (p < 0.01, n = 13), while blood-flow increased by about 25% on Day 21 (p < 0.01, n = 13) compared to that in C57 mice. Histological analysis of both control and amputated limbs indicated an approximately 70% increase in the number of vessels (both arterial and venous) in MRL mice over that of the C57 mice (p < 0.05, n = 3). We conclude that higher blood flow and angiogenesis may play an important role in facilitating the fast regrowth ratios of amputated digits in MRL mice compared to C57 mice.

Relativistic electron avalanches as a thunderstorm discharge competing with lightning.

Gamma-ray 'glows' are long duration (seconds to tens of minutes) X-ray and gamma-ray emission coming from thunderclouds. Measurements suggest the presence of relativistic runaway electron avalanches (RREA), the same process underlying terrestrial gamma-ray flashes. Here we demonstrate that glows are relatively a common phenomena near the tops of thunderstorms, when compared with events such as terrestrial gamma-ray flashes. Examining the strongest glow measured by the airborne detector for energetic emissions, we show that this glow is measured near the end of a downward RREA, consistent with occurring between the upper positive charge layer and the negative screening layer above it. The glow discharges the upper positive layer by ≥9.6 mA, strong enough to be an important charging mechanism of the storm. For this glow, the gamma-ray flux observed is close to the value at which relativistic feedback processes become important, with an avalanche multiplication factor of 4,500.

Upward electrical discharges observed above Tropical Depression Dorian.

Observation of upward electrical discharges from thunderstorms has been sporadically reported in the scientific literature. According to their terminal altitudes, they are classified as starters (20-30 km), jets (40-50 km) and gigantic jets (70-90 km). They not only have a significant impact on the occupied atmospheric volumes but also electrically couple different atmospheric regions. However, as they are rare and unpredictable, our knowledge of them has been built on observations that typically record only one type of such discharges. Here we report a close-distance observation of seven upward discharges including one starter, two jets and four gigantic jets above Tropical Depression Dorian. Our optical and electromagnetic data indicate that all events are of negative polarity, suggesting they are initiated in the same thundercloud charge region. The data also indicate that the lightning-like discharge channel can extend above thunderclouds by about 30 km, but the discharge does not emit low-frequency electromagnetic radiation as normal lightning.

Seroprevalence of cytomegalovirus among pregnant women attending Murtala Mohammed Specialist Hospital Kano, Nigeria.

BACKGROUND: Primary Cytomegalovirus (CMV) infection during pregnancy is a frequent and serious threat to the fetus. As there is no vaccine alternative measures are needed to prevent congenital CMV infection. OBJECTIVE: This study determined CMV Immunoglobulin G (IgG) antibody among pregnant women in order to ascertain the immune status of mothers to guide policy makers. METHODS: A semi-structured questionnaire was initially administered to obtain information on demographic details, stage of pregnancy and risk factors. Blood was collected by venipuncture from 180 women attending the antenatal clinic in Murtala Mohammed Specialist Hospital Kano, Kano State, Nigeria. Sera samples were screened using CMV IgG ELISA kit (Dialab, Austria). RESULTS: Out of 180 pregnant women, 164 (91.1%) were seropositive. Based on stages of pregnancy 6/6(100%), 52/60(86.7%) and 106/114(93.0%) were seropositive among women in the first, second and third trimesters respectively. CONCLUSION: Seroprevalence of pregnant women to CMV Ig G is high, hence the need for CMV - IgM screening to know the extent of active infection. There is also need for public enlightenment on the methods of transmission, effective prevention and control strategies.

Worth a thousand words: Integrating clinical photographs into an electronic medical record.

Technological advances have made clinical photographs ubiquitous but the tremendous value of images is often burdened by concerns that are both legitimate and unsubstantiated. Compliant photos dramatically improve patient value and should be encouraged after adequate institutional preparation. As healthcare networks continue to transition to electronic medical records, clinicians and administrators should outline reasonable policies to integrate photos safely.

Implication of vaccination on measles reduction and elimination in Nigeria.

BACKGROUND: The availability of a safe and effective vaccine has encouraged the establishment of measles mortality reduction and elimination goals in six World Health Organization regions. In the WHO-AFRO region, they intend to eliminate measles by 2020. This initiative led to the successful elimination of measles in 2012 in the American region. This study mined data from independent investigations in two geographical regions in Nigeria in order to observe the prospects of preventive measures against wild measles virus in a resource limited setting. MATERIALS AND METHODS: Retrospective data from 757 children between the ages of 10 months and 13years were used. 500 were from children in Kano, Northwest Nigeria and 257 from children in Ibadan, Southwest Nigeria. Data analysis was done using SPSS 16.0. RESULTS: In all, 386 (75.4%) of the vaccinated children were protected while 121 (23.6%) were not protected. In the unvaccinated children, 63 (25.7%) were protected while 135 (55.1%) were not protected (X2=120.919, p=0.000). In Kano, 81 % of the vaccinated children were protected while 18.4% were not protected. In Ibadan, 95% of the vaccinated were protected (X2=22.129, p = 0.000). CONCLUSION: The herd immunity in both Kano and Ibadan is good enough to reduce wild measles virus infection. This finding is encouraging because Kano has suffered several epidemics prior to the vaccination campaigns resulting from religious apathy which is the bane of vaccination efforts. Here is evidence that with the right approach in Northern Nigeria, it is possible to sustain national and global immunization drive.

MRI assessment of biliary ductal obstruction: is there added value of T1-weighted gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MR cholangiography?

OBJECTIVE: The goal of the present study was to determine the added value of gadolium-ethoxybenzyl-diethylenetriamine pentaacetic acid (gadoxetate disodium)-enhanced magnetic resonance cholangiography (MRC) to standard liver MRI including T2-weighted MRCP in assessment of biliary ductal obstruction. MATERIALS AND METHODS: Thirty-eight patients (mean age, 48.1 ± 16.7 years) (40 total examinations) who underwent liver MRI (including T2-weighted MRCP and gadoxetate disodium-enhanced MRC) for suspicion of biliary disease were included in this institutional review board-approved, HIPAA-compliant retrospective study. Three blinded radiologists first evaluated MR images without gadoxetate disodium-enhanced MRC for presence and significance of biliary obstruction, underlying cause for obstruction, and confidence in final diagnosis. After inclusion of gadoxetate disodium-enhanced MRC, readers again determined presence and significance of biliary obstruction and confidence in final diagnosis. Reference standard was established using MRI along with ERCP, percutaneous transhepatic cholangiography, intraoperative cholangiography, or a combination thereof. RESULTS: Overall sensitivity across all readers in diagnosing significance of obstruction was 60% without gadoxetate disodium-enhanced MRC and 91% with gadoxetate disodium- enhanced MRC (p < 0.001). Across all readers, assessment of significance of obstruction was changed when adding gadoxetate disodium-enhanced MRC in 40 of 120 cases (33%); significance of obstruction was correctly changed in 35 of 40 cases (87.5%). Biliary obstruction was graded of unknown significance in 27 of 120 cases (22.5%) across all readers when gadoxetate disodium-enhanced MRC was not reviewed. Significance of biliary obstruction was classified correctly after adding gadoxetate disodium-enhanced MRC in 25 of these 27 cases (93%). Confidence in final diagnosis was significantly higher with addition of gadoxetate di-sodium-enhanced MRC for two of three readers (p < 0.003). CONCLUSION: Addition of gadoxetate disodium-enhanced MRC to liver MRI significantly improves sensitivity in assessing significance of biliary obstruction and can improve reader confidence in establishing a final diagnosis. This added information could have a substantial impact in the determination of the most appropriate therapeutic options.

The pentacyclic triterpenoids in herbal medicines and their pharmacological activities in diabetes and diabetic complications.

Pentacyclic triterpenoids including the oleanane, ursane and lupane groups are widely distributed in many medicinal plants, such as Glycyrrhiza species, Gymnema species, Centella asiatica, Camellia sinensis, Crataegus species and Olea europaea, which are commonly used in traditional medicine for the treatment of diabetes and diabetic complications. A large number of bioactive pentacyclic triterpenoids, such as oleanolic acid, glycyrrhizin, glycyrrhetinic acid, ursolic acid, betulin, betulinic acid and lupeol have shown multiple biological activities with apparent effects on glucose absorption, glucose uptake, insulin secretion, diabetic vascular dysfunction, retinopathy and nephropathy. The versatility of the pentacyclic triterpenes provides a promising approach for diabetes management.

Formation of streamer discharges from an isolated ionization column at subbreakdown conditions.

This Letter reports a modeling study on the formation of streamer discharges from an isolated ionization column under subbreakdown condition. Numerical simulations show that positive streamers are able to form from the tip of an ionization column in a uniform applied electric field well below the breakdown threshold field. However, even when the applied field approaches the breakdown threshold field, negative streamers fail to originate from the other tip of the ionization column after the positive streamer has propagated a certain distance. The results reported explain some puzzling observations on streamer discharges in nature such as the predominant initiation of sprites by downward propagating positive streamers and help advance the initiation theories of sprites and lightning.

Comparative antioxidant activity study of some commonly used spices in Bangladesh.

Many spices have been shown to impart an antioxidative effect in foods. This study summarized the literature on the antioxidative effects of spices. The term spice is defined as dry plant material that is normally added to food to impart flavor. The methanolic crude extracts of Allium sativum, Coriandrum sativum, Cuminum cyminum, Zingiber officinale, Cinnamomum verum, Elettaria cardamomum and Cinnamomum tamala were screened for their free radical scavenging properties using ascorbic acid as standard antioxidant. Free radical scavenging activity was evaluated using 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical. The overall antioxidant activity of Cuminum cyminum was found to be the strongest, followed in descending order by Z. officinale, C. sativum, A. sativum, C. tamala, C. verum, E. cardamomum. The IC50 values of the extracts ranged between 15.48 and 217.431 (microg mL(-1)). The ascorbic acid levels was 22.78 (microg mL(-1)) the present study revealed that the selected plants would exert several beneficial effects by virtue of their antioxidant activity and could be harnessed as drug formulation.

Studies of various biochemical parameters of rat plasma following chronic administration of "Rohitakarista"-an Ayurvedic formulation.

The study was carried out to investigate the safety profile as well as the effect of "Rohitakarista" (RHT) on various biochemical parameters of rats' plasma after chronic administration. RHT, a classical Ayurvedic preparation used in hepatosplenic disorders, was administered per oral route at a dose of 100 mg kg(-1) body weight, once daily, up to 46 days for all the experiments. Forty albino rats (Rattus novergicus: Sprague-Dawley strains), equally of both sexes, were randomly grouped into four where each group had ten animal/sex. One male and one female group were used as control and other groups were used as test. In the male, rats there was a statistically insignificant increase (p = 0.763) in the total protein but there was a statistically significant increase (p = 0.022) in the total protein content of the plasma of female rats. Statistically very high significant increase (male: p = 0.001 and female: p = 0.001) in the albumin content of the plasma was noted in both sexes. In case of bilirubin, interestingly it was decreased very high significantly (p = 0.001) in plasma of male rats but increased very high significantly (p = 0.001) in the plasma of female rats. In the male rats, statistically there was a very high significant decrease (sGPT: p = 0.001, sGOT: p = 0.001 and ALP: p = 0.001) in the sGPT, sGOT and ALP activities in the plasma. On the other hand, statistically there was a very highly significant increase (sGPT: p = 0.001, sGOT: p = 0.001 and ALP: p = 0.001) in the sGPT, sGOT and ALP activities in the plasma of female rats. Very high significant decrease (male: p = 0.001 and female: p = 0.001) in creatinine in plasma of both sexes were observed after chronic administration of RHT. Urea in the plasma was decreased very high significantly (p = 0.001) in plasma of male rats but increased very high significantly (p = 0.001) in the plasma of female rats. There was high significant increase (p = 0.002) in uric acid in male rats. On the contrary, no significant increase (p = 0.324) of uric acid was observed in female rats.