Case Report for Two Siblings Carrying Neurofibromatosis Type 1 with a Rare NF1: c.5392C>T Mutation.

Neurofibromatosis type 1 (NF1) is a neurocutaneous syndrome caused by mutations on the NF1 gene, which is located at chromosome 17q11.2. Although an autosomal dominant inheritance pattern is well-established, about half of new cases are the result of de novo NF1 mutations. Neurofibromatosis type 1 has an incidence rate of 1/2600-3000 individuals, making it a major public health problem. The product of the NF1 gene, the neurofibromin protein, is known to play a critical role in cellular differentiation and in tumor suppression. Due to widespread expression of neurofibromin in numerous tissues, particularly in cutaneous and nervous systems, NF1 mutations cause a wide variety of clinical symptoms, including cutaneous and ocular lesions such as café au lait spots, axillary and inguinal freckling, multiple cutaneous neurofibromas, iris Lisch nodules, choroidal freckling and internal tumors. In this article, we report the cases of two siblings with NF1, a 21-year-old male and his 24-year-old sister, who have the same c.5392C>T mutation on the NF1 gene (p.Gln1798 Ter). Café au lait macules and freckling were the prominent clinical features in both siblings. However, a plexiform neurofibroma was also observed on the left arm of the sister, which is known to carry potential risk for malignant transformation. Although the mutation was previously described once, to the best of our knowledge, no case report has been published since then.

Involvement of spinal cannabinoid receptors in the antipruritic effects of WIN 55,212-2, a cannabinoid receptor agonist.

BACKGROUND: Cannabinoids have been used for their analgesic and euphoric effects for millennia, but recently the antipruritic effects of cannabis have been discovered. Considering the similarities between pain and itch sensations, we hypothesized that cannabinoid receptors may play a role in the antipruritic effects of cannabinoids. AIM: To analyse the role of the spinal cannabinoid receptors, CB1 and CB2, in the antipruritic effects of the cannabinoid agonist WIN 55,212-2. METHODS: Male Balb/c mice weighing 20-30 g were used. Scratching behaviour in the mice was produced by injection of serotonin 5 µg/50 µL intradermally into the nape of the neck. Scratching of the site of injection by the hind paws was video-recorded for 30 min. After testing different doses of WIN 55,212-2 [1, 3 and 10 mg/kg intraperitoneally (IP)], the effects of the CB1 receptor antagonist, AM-251 [1 µg/mouse administered intrathecally (IT)] and the CB2 receptor antagonist AM-630 (4 µg/mouse IT) on the antipruritic effects of WIN 55,212-2 were studied using a rotarod apparatus. RESULTS: WIN 55,212-2 (1, 3 or 10 mg/kg IP) dose-dependently decreased serotonin-induced scratches. The receptor antagonist CB1 partially reversed the effects of WIN 55,212-2 (P < 0.05); whereas CB2 had no statistically significant effect. WIN 55,212-2 impaired motor function only at the highest dose given (10 mg/kg, P < 0.05). CONCLUSIONS: Our findings support prior researches indicating that cannabinoids exert antipruritic effects. Moreover, our results show that the antipruritic effects of cannabinoids are partially mediated by spinal CB1 receptors.

Starch/PCL composite nanofibers by co-axial electrospinning technique for biomedical applications.

BACKGROUND: In this study, starch and polycaprolactone (PCL), composite nanofibers were fabricated by co-axial needle electrospinning technique. Processing parameters such as polymer concentration, flow rate and voltage had a marked influence on the composite fiber diameter. Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), mechanical and physical properties (such as density, viscosity and electrical conductivity) of the composite fibres were evaluated. Moreover, a cell culture test was performed in order to determine their cytotoxicity for wound dressing application. RESULTS: The effect of starch ratio in the solution on the properties and morphological structure of the fibers produced was presented. With lower starch concentration values, the fibers have greater ultimate tensile strength characteristic (mostly 4 and 5 wt%). According to SEM results, it can be figured out that the nanofibers fabricated have good spinnability and morphology. The mean diameter of the fibers is about 150 nm. According to results of cell culture study, the finding can be determined that the increase of starch in the fiber also increases the cell viability. CONCLUSIONS: Composite nanofibers of starch/PCL have been prepared using a co-axial needle electrospinning technique. PCL was successfully encapsulated within starch. Fiber formation was observed for different ratio of starch. With several test, analysis and measurement performed, some important parameters such as quality and effectuality of each fiber obtained for wound dressing applications were discussed in detail.

The role of macrophages in the pathogenesis of mycosis fungoides.

BACKGROUND: Macrophages are classified into classically activated (M1) and alternatively activated (M2) macrophages. Decrease in macrophage number in tumour tissue with treatment has been reported. AIM: The aim of this study was to determine whether treatment has an effect on the number of dermal M1 and M2 macrophages in patients with mycosis fungoides (MF). METHODS: In total, 21 patients (8 women, 13 men; age range 42-73 years) were included in this study. We determined markers for dermal M1 (inducible nitric oxide synthase and CD68) and M2 (markers: CD163 and CD206) macrophages using double immunohistochemistry to reduce the error rate, and then counted the cells. RESULTS: The number of dermal M1 cells was significantly lower pretreatment compared with post-treatment (P < 0.01). The numbers of dermal M2 cells were also numerically decreased by treatment. These results did not change significantly after exclusion of the patients who had recurrence (n = 2). There were no statistically significant differences between groups classified by stage, lesion type or treatment outcome. CONCLUSION: Macrophage numbers are decreased in MF after treatment of tumour tissue.

Corticosteroid hypersensitivity in allergic rhinitis.

Corticosteroid hypersensitivity in allergic rhinitis. BACKGROUND: intranasal corticosteroid (IC) is the most effective treatment method in allergic rhinitis patients who are unresponsive to antihistamines. The literature reports an approximate 20% treatment failure for instances where IC is used for the treatment allergic rhinitis. Hypersensitivity reaction to corticosteroids may be one of the causes of this treatment failure. OBJECTIVE: to discover the incidence and confounding factors of corticosteroid hypersensitivity in patients with allergic rhinitis. METHODS: after 31 patients were excluded, 150 consecutive patients who were prospectively evaluated in our outpatient clinics with the diagnosis of allergic rhinitis and 50 age- and sex- matched healthy volunteers were included in this study. To diagnose allergic rhinitis, the symptoms of patients and a skin prick test were used. A skin patch test was used to determine corticosteroid hypersensitivity. Total IgE values and total eosinophil count were obtained for all patients. Total symptom scores were calculated for the severity of symptoms and to determine the response to therapy using intranasal corticosteroids. RESULTS: the incidence of corticosteroid hypersensitivity determined via the skin patch test was 14.0% (21 out of 150 patients). A difference was observed for patch test positivity results between the study and control groups (14% vs. 0%, respectively). Serum IgE levels and total eosinophil count were higher among patients who had corticosteroid hypersensitivity (p:0.005 and p:0.004, respectively). Patients unresponsive to intranasal corticosteroids had a higher incidence of corticosteroid hypersensitivity (71.4% vs. 4.4%, p<0.00 1). CONCLUSION: our study is the largest to date investigating CH in patients with allergic rhinitis and patients with allergic rhinitis have been found to have a high incidence (14%) of corticosteroid hypersensitivity, which may affect the response of patients to intranasal corticosteroid treatment.

Ankylosing spondylitis and a diagnostic dilemma: coccydynia.

OBJECTIVES: Coccydynia is defined as pain in or around the tail bone area. The most common cause of coccydynia is either a trauma such as a fall directly on to the coccyx or repetitive minor trauma. The etiology remains obscure in up to 30% of patients. The literature on the contribution of rheumatic diseases to coccydynia is scarce. Our objective was to investigate the prevalence of coccydynia in ankylosing spondylitis (AS) patients. METHODS: One hundred and seven consecutive patients with AS were evaluated for coccydynia were enrolled between January and November 2012 for a cross-sectional analysis. Seventy-four consecutive patients were followed for mechanical back pain as controls and the AS patients were interviewed for the presence of coccydynia. The data collected was evaluated on SPSS® version 11.5 and Microsoft Excel® Programmes. RESULTS: Prevalence of coccydynia in AS (38.3%) was significantly higher than the control group (p<0.0001) in both female and male AS patients (female AS vs. control=40.9% vs. 18.4%, p=0.015 and male AS vs. control=36.5% vs. 8.0%, p=0.005). Both genders were affected equally in the AS group whereas coccydynia was slightly more frequent in female patients in the control group. CONCLUSIONS: Coccydynia is a previously neglected symptom of AS and it is almost three times more common in AS than in non-specific chronic low back pain. Our observation may implicate that inflammatory diseases have a role in the etiology of coccydynia, especially in those without a history of recent or past trauma and coccydynia may be a factor associated with the severity of AS as well.

Predictive factors for treatment success of epidural steroid injections in patients with lumbar spinal surgery.

OBJECTIVE: The efficacy of epidural steroid injections (ESIs) in the treatment of radicular pain in patients undergoing lumbar spinal surgery is still unclear. The aim of this study was to investigate the factors affecting the success of ESIs in the treatment of ongoing radicular pain in patients undergoing lumbar spinal surgery. PATIENTS AND METHODS: This study was designed as a single-center, retrospective study, and was conducted at a Pain Management Center of a tertiary care center. A total of 260 patients with failed back surgery syndrome who received fluoroscopy-guided lumbar ESI were included. Treatment success was defined as ≥50% reduction in the numeric rating scale score at the one-month follow-up. The patients were divided into the treatment success and the treatment failure groups. RESULTS: The presence of spinal instrumentation was significantly lower in the treatment success group (p=0.045). Symptom duration and the numeric rating scale score at 1 hour were significantly lower in the treatment success group (p<0.05). The use of triamcinolone acetonide in the treatment success group was found to be significantly higher than in the treatment failure group (p=0.027). CONCLUSIONS: The short duration of symptoms and the absence of instrumentation seem to be prognostic factors that positively affect the success of ESI treatment in operated patients. A ≥50% pain reduction in the first hour after the procedure is a valuable indicator that treatment success can be achieved in the short term. Finally, the steroid type can also affect the treatment results.

Correlation between 25-hydroxy vitamin D levels and COVID-19 severity in pregnant women: a cross-sectional study.

OBJECTIVE: To evaluate the relationship between 25-hydroxy vitamin D (25(OH)D) levels and disease severity in hospitalized COVID-19 positive pregnant women. METHODS: The COVID-19 (+) pregnant women (confirmed by PCR test) were classified as asymptomatic, mild symptomatic, and severe disease according to their symptoms and laboratory results. Severe COVID-19 criteria were respiratory symptoms and/or findings. The following laboratory results were considered as poor prognostic factors: the number of lymphocytes <800/µl and/or CRP value >10 times the upper limit of the normal range and/or ferritin value >500 ng/ml and/or D-Dimer value >1000 µg/l. The patients were divided into two groups; asymptomatic or mild symptomatic group (Group 1), and severe disease and/or poor prognostic factor group (Group 2). The 25(OH)D levels were compared between groups. ROC curve analysis was used to analyze the cutoff value for vitamin D to predict the severity of COVID-19. RESULTS: 25(OH)D levels were found to be statistically significantly lower in group 2 (15.5 (10.25) ng/ml in Group 1, 13 (12) ng/ml in Group 2, p = .010). The 25(OH)D level under 14.5 ng/ml was associated with severe COVID-19 and/or poor prognostic factors (p = .010). The risk of severe COVID-19 and/or having poor prognostic factors was 1.87 times higher among pregnant women who had 25(OH)D levels below 14.5 ng/ml. This value was found to have 54.1% sensitivity and 61.3% specificity in predicting severe COVID-19 and/or poor prognostic laboratory findings in pregnant women. CONCLUSION: There is a relationship between vitamin D status and the severity of COVID-19 in pregnant women. During the pandemic period, vitamin D supplementation for pregnant women should gain more importance.

Olfactory bulb volume and olfactory sulcus depth in patients with Behçet's disease.

OBJECTIVE: To investigate olfactory bulb volume and olfactory sulcus depth in patients with Behçet's disease, using magnetic resonance imaging. METHODS: Cranial magnetic resonance imaging scans of 27 adults with Behçet's disease (10 males and 17 females) and 27 healthy controls were examined. Olfactory bulb volume and olfactory sulcus depth were measured on coronal, T2-weighted, spectral pre-saturation with inversion recovery sequences. RESULTS: Bilateral olfactory bulb volume and right-sided olfactory sulcus depth were significantly lower in the Behçet's disease group than in the control group (p < 0.05). Left-sided olfactory sulcus depth increased with Behçet's disease duration. In both groups, olfactory bulb volume was significantly higher in the left than the right side. There were no gender differences for olfactory bulb volume and olfactory sulcus depth. Positive correlations were determined between right- and left-sided olfactory bulb volume values and between right- and left-sided olfactory sulcus depth values. CONCLUSION: Behçet's disease may decrease olfactory functions, related to lower olfactory bulb volume and olfactory sulcus depth. The affected vascular system and possibly damaged neural system, nasal mucosal lesions, and prolonged nasal mucociliary clearance time may cause olfactory dysfunction. Patient follow up is recommended, with magnetic resonance imaging examinations of the olfactory system if necessary.

The influence of stream bed hydraulic conductivity on sustaining baseflow in rivers.

This study presents the results of the influence of stream bed hydraulic conductivity on baseflow sustainability by using a coupled model of surface and subsurface hydrology. The model provides a coupled solution to the dynamic interactions between a river and a surfacial aquifer and is used to numerically study the effect of stream bed conductivity on the overall system response. To achieve this objective, the model is formulated to include a one-dimensional river flow model and a two-dimensional vertically averaged groundwater flow model in an unconfined aquifer. The coupling is achieved at the river bed via a hydraulic flux that is described as a function of river bed conductivity and the gradient between river stage and groundwater head. The model incorporates the concept of simultaneous presence of the two hydrologic processes for simulating the dynamic interactions and uses a novel numerical technique to solve the two systems concurrently. These interactions are analyzed by numerical experimentation under different hydraulic conductivity conditions. The influence of hydraulic conductivity and hydraulic gradient is studied under steady and unsteady flow regimes to assess the occurrence of baseflow. The analysis also reveals critical insights into the governing mechanisms that provide and sustain the baseflow in rivers.

Analysis of the anti-allodynic effects of combination of a synthetic cannabinoid and a selective noradrenaline re-uptake inhibitor in nerve injury-induced neuropathic mice.

BACKGROUND: Combining drugs not only reduces specific adverse effects of each of the drug at a higher dose but also may lead to enhanced efficacy. Tapentadol is a recently discovered analgesic possessing µ-opioid receptor agonism and noradrenaline re-uptake inhibition in a single molecule. Taking into consideration, the pharmacological similarities between opioids and cannabinoids, we assumed that combination of cannabinoids with noradrenaline re-uptake inhibitors might also be effective. We therefore aimed to determine whether combining 1:1, 1:3 and 3:1 fixed ratios of the synthetic cannabinoid WIN 55,212-2 and the selective noradrenaline re-uptake inhibitor maprotiline exert anti-allodynic synergy on nerve-injured neuropathic mice. METHODS: Partial tight ligation of the sciatic nerve was made in mice; on pre-operative and post-operative 15 days basal mechanical allodynia, cold allodynia and motor function were assessed using von Frey filaments, hot/cold plate and rota rod apparatus. RESULTS: Mechanical and cold allodynia developed in all groups on post-operative 15 days. Development of cold allodynia was statistically significant in all groups (p < 0.05); therefore, cold allodynia was used in combination studies. As shown by isobolographic analysis, interactions of 1:1 and 3:1 ratios of WIN 55,212-2:maprotiline combinations were supra-additive, whereas 1:3 ratio was sub-additive. CONCLUSIONS: Overall, our data suggest that combination of a cannabinoid with a selective noradrenaline re-uptake inhibitor may offer a beneficial treatment option for neuropathic pain.

Depression and psychosocial factors in Turkish women with fibromyalgia syndrome.

AIM: The aim of this study was to evaluate the demographic qualifications, frequency of depression, degree of pain, and the correlations between these factors in Turkish women with fibromyalgia syndrome (FS). METHODS: Fifty-three women with FS and 54 healthy women were included in the study. The visual analogue scale (VAS) was applied to evaluate the degree of pain and Beck depression inventory (BDI) for depression. RESULTS: Mean age of the FS and the healthy women groups was 42.6+/-9.6 (21-63) and 39.4+/-13.2 (24-60) years respectively; which were statistically similar (P>0.05). Of the patients, 69.8% were married, and the mean years of education was 8.7+/-4.8 years. Marriage among relatives was found in 18.4% of the patients. The mean VAS score of the patients was 7.2+/-1.7 cm with the mean duration of pain 5+/-4.6 years. Mean BDI scores of FS patients and the healthy group were 15.7+/-8.7 and 10.2+/-5.5 respectively; the difference between the 2 groups was statistically significant (P<0.05). According to the BDI scores, 90% of FS patients were classified as depressed; among them, 50% had minor, 38% moderate, and 2% severe depression. FS patients who were married to a relative had higher scores of BDI (r=0.414, P=0.013). There was negative correlation between BDI score and patients' total year of education (r=-0.295, P=0.037); and the husband's education level (r=-0.367, P=0.030). According to BDI, the c2 test revealed significant depression in patients with sleep-disorders (P=0.009). CONCLUSIONS: We found a significant degree of depression in Turkish female FS patients. This situation is found to be correlated with the education level of both patient and husband; marital status, and sleep-disorder; it is suggested that these factors should be taken into consideration in the diagnosis, treatment and follow-up of FS patients.

Involvement of Descending Serotonergic and Noradrenergic Systems and their Spinal Receptor Subtypes in the Antinociceptive Effect of Dipyrone.

The antinociceptive effect of dipyrone is partly due to its action upon pain-related central nervous system structures. Despite intensive research, the precise mechanisms mediating its analgesic effects remain unclear. Here, we aimed to determine whether neurotoxic destruction of descending inhibitory pathways affect dipyrone-induced antinociception and whether various spinal serotonergic and adrenergic receptors are involved in this antinociception. The nociceptive response was assessed by the tail-flick test. Mice injected with dipyrone (150, 300, 600 mg/kg, i.p.) elicited dose-related antinociception. The neurotoxins 5,7-dihydroxytryptamine (50 µg/mouse) and 6-hydroxydopamine (20 µg/mouse) are applied intrathecally to deplete serotonin and noradrenaline in the spinal cord. 3 days after neurotoxin injections, a significant reduction in the antinociceptive effect of dipyrone was observed. Intrathecal administration of monoaminergic antagonists (10 µg/mouse), the 5-HT2a antagonist ketanserin, the 5-HT3 antagonist ondansetron, the 5-HT7 antagonist SB-258719, α1-adrenoceptor antagonist prazosin, α2-adrenoceptor antagonist yohimbine, and the ß-adrenoceptor antagonist propranolol also attenuated dipyrone antinociception. We propose that descending serotonergic and noradrenergic pathways play pivotal role in dipyrone-induced antinociception and spinal 5-HT2a, 5-HT3, and 5-HT7-serotonergic and α1, α2, and ß-adrenergic receptors mediate this effect.

Electrohydrodynamic Preparation of Nanomedicines.

The preparation of nanomedicines can be achived using a host of methods ranging from wet-chemical approaches to more engineering related techniques. As a maturing branch of nanotechnology, nanomedcines are being tailored to serve multiple pharmaceutic and biomedical related funcitons (e.g. targeted delivery, imaging, healing, sensing which may require the utilisaiton of one or more actives or excipients. In some instances, handling of materials (such as sensitive biomolecules or active pharmaceutical ingredient) becomes a limiting factor along with issues related to fabrication steps (loss or degradation of active components and functional materials, deposition location & procedure (removal of formed structures, process environment sensitivity and scale-up potential. This short review focuses on the electrohydrodynamic preparation of emerging nanomedicines that have potential to serve as therapeutic platforms. An insight into the underpinning process (jet-formation, related paramerts (material and process and strucutral outcomes (particles and fibres is given in relation to highlighted research. The ambient temperature processing, user friendly preparation and present industrial scale up potential (now in kg/hr make such processes valuable in the preparation of future nano-scaled and sensitive dosage forms.

Value of Examination Under Fluoroscopy for the Assessment of Sacroiliac Joint Dysfunction.

BACKGROUND: Pain emanating from the sacroiliac (SI) joint can have variable radiation patterns. Single physical examination tests for SI joint pain are inconsistent with multiple tests increasing both sensitivity and specificity. OBJECTIVE: To evaluate the use of fluoroscopy in the diagnosis of SI joint pain. STUDY DESIGN: Prospective double blind comparison study. SETTING: Pain clinic and radiology setting in urban Veterans Administration (VA) in New Orleans, Louisiana. METHODS: Twenty-two adult men, patients at a southeastern United States VA interventional pain clinic, presented with unilateral low back pain of more than 2 months' duration. Patients with previous back surgery were excluded from the study. Each patient was given a Gapping test, Patrick (FABERE) test, and Gaenslen test. A second blinded physician placed each patient prone under fluoroscopic guidance, asking each patient to point to the most painful area. Pain was provoked by applying pressure with the heel of the palm in that area to determine the point of maximum tenderness. The area was marked with a radio-opaque object and was placed on the mark with a fluoroscopic imgage. A site within 1 cm of the SI joint was considered as a positive test. This was followed by a diagnostic injection under fluoroscopy with 1 mL 2% lidocaine. A positive result was considered as more than 2 hours of greater than 75% reduction in pain. Then, in 2-3 days this was followed by a therapeutic injection under fluoroscopy with 1 mL 0.5% bupivacaine and 40 mg methylprednisolone. RESULTS: Each patient was reassessed after 6 weeks. The sensitivity and specificity in addition to the positive and negative predictive values were determined for both the conventional examinations, as well as the examination under fluoroscopy. Finally, a receiver operating characteristic (ROC) curve was constructed to evaluate test performance. The sensitivity and specificity of the fluoroscopic examination were 0.82 and 0.80 respectively; Positive predictive value and negative predictive value were 0.93 and 0.57 respectively. The area under ROC curve was 0.812 which is considered a "good" test; however the area under ROC for the conventional examination were between 0.52-0.58 which is considered "poor to fail". LIMITATIONS: Variation in anatomy of the SI joint, small sample size. CONCLUSIONS: Multiple structures of the SI joint complex can result in clinical symptoms of pain. These include intra-articular structures (degenerative arthritis, and inflammatory conditions) as well as extra-articular structures (ligaments, muscles, etc.).

Preparation and evaluation of cerium oxide-bovine hydroxyapatite composites for biomedical engineering applications.

The fabrication and characterization of bovine hydroxyapatite (BHA) and cerium oxide (CeO2) composites are presented. CeO2 (at varying concentrations 1, 5 and 10wt%) were added to calcinated BHA powder. The resulting mixtures were shaped into green cylindrical samples by powder pressing (350MPa) followed by sintering in air (1000-1300°C for 4h). Density, Vickers microhardness (HV), compression strength, scanning electron microscopy (SEM) and X-ray diffraction (XRD) studies were performed on the products. The sintering behavior, microstructural characteristics and mechanical properties were evaluated. Differences in the sintering temperature (for 1wt% CeO2 composites) between 1200 and 1300°C, show a 3.3% increase in the microhardness (564 and 582.75HV, respectively). Composites prepared at 1300°C demonstrate the greatest compression strength with comparable results for 5 and 10wt% CeO2 content (106 and 107MPa) which are significantly better than those for 1wt% and those that do not include any CeO2 (90 and below 60MPa, respectively). The results obtained suggest optimal parameters to be used in preparation of BHA and CeO2 composites, while also highlighting the potential of such materials in several biomedical engineering applications.

SAPHO syndrome: misdiagnosed and operated.

SAPHO is a rare disorder that results in synovitis, acne, pustulosis, hyperostosis and osteitis. Patients with this syndrome typically present with musculoskeletal complaints, frequently localized to the anterior chest wall. However, diagnosis can be difficult in case of involvement of only one symptomatic bone without skin lesions. Awareness of SAPHO syndrome is necessary for accurate diagnosis and to prevent inappropriate and unnecessary treatment.

Reflex sympathetic dystrophy arising in a patient with familial Mediterranean fever.

A 14-year-old girl with familial Mediterranean fever (FMF) had had acute attacks of fever, abdominal pain, and arthritis for 4 years. Her last arthritis attack was protracted, leading to reflex sympathetic dystrophy (RSD) in her right lower extremity. Physical therapy along with sympathetic ganglion block and corticosteroid therapy was used for the treatment. To our knowledge, this is the first reported case of RSD arising in a patient with FMF. Early recognition of RSD in FMF patients is important, and physical therapy should be applied along with medical treatment.