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1.

Purpose

This study aims to investigate nerve distribution patterns of human lower leg skeletal muscles using a modified Sihler’s staining method.

Methods

Sixteen lower leg from eight fresh adult cadavers were used in this study and all the skeletal muscles were dissected. The muscle specimens were classified according to Lim’s classification. The specimens were then stained by further modified Sihler’s staining technique. Data were analyzed according to research results.

Results

After the staining, we found four patterns of nerve distribution in human lower leg muscles: (1) Type 1: single nerve pattern in which the nerve branches into two either running parallel to each other or radiating in a spray pattern (such as the extensor digitorum longus, extensor hallucis longus, fibularis brevis and flexor hallucis longus). (2) Type 2: double nerve pattern, one being proximal and the other being distal (such as the extensor digitorum longus, flexor digitorum longus, flexor hallucis longus). (3) Type 3: multiple branch pattern (such as the tibialis anterior, fibularis longus, gastrocnemius, soleus, tibialis anterior and popliteus).

Conclusion

Our modified Sihler’s staining method is useful for research of large muscles and intramuscular nerves in human. These findings might provide guidance for clinicians for muscle reconstruction surgery.
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2.

Objective

We describe our experience for repair septal perforation with a septal flap and we analyse the route of the septal branch of the anterior ethmoidal artery (AEA) in the septum area with a radiological anatomy study in order to perform this flap.

Study design

We carry out a prospective analysis with computed tomography scan in the cadaver heads and we perform an endoscopic technique in the patients.

Methods

Ten nasal cavities were analysed in five adult cadaveric heads and two patients diagnosed with anterior septal perforation were surgically treated. Measurements in the cadaveric heads were obtained from a sagittal plane of the nasal septum. The anterior point corresponds to the projection of the anterior insertion of the middle turbinate in the frontal process of the maxilla over the nasal septum. The posterior point was obtained with a vertical line passing through the entrance of the AEA in the nasal septum.

Results

The mean distance between the anterior point and the posterior point was 7.35 mm with a standard deviation of 0.95 mm. The lowest value was 5.5 mm and the highest value was 8.7 mm. We observed good epithelialisation and closure of the perforation in all patients.

Conclusion

The unilateral septal flap pedicle by anterior ethmoidal artery may be used for small and medium perforations with a pedicle smaller than 1 cm posterior to the axilla.
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3.

Purpose

Adenosine deaminase 2 (ADA2) have been reported to cause vasculitic diseases and immunodeficiency recently. Patients present with stroke episodes and rashes mimicking polyarteritis nodosa (PAN). We report a patient who has been followed up with severe neutropenia and found an unexpectedly revealed novel mutation in CECR1 affecting ADA2.

Methods

We reviewed medical records and clinical history of the patient. No mutations in other known neutropenia genes such as ELA, G6PC3, HAX1, AP3B1, LAMTOR2, VPS13B, VPS45, GFI1, JAGN1, or WAS could be detected. Sanger sequencing was used to confirm the genetic variants in the patient and relatives.

Results

Genetic analysis by exome sequencing revealed a novel mutation in the gene CECR1 (c.G962A; p.G321E) which segregated perfectly in the relatives.

Conclusion

This is the first DADA2 patient presenting with severe neutropenia. We suggest that in patients with unexplained cytopenias combined with immunodeficiency, fevers of unknown origin and high inflammation markers, DADA2 should be considered.
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4.

?

Helicobacter bilis is a commensal bacterium causing chronic hepatitis and colitis in mice. In humans, enterohepatic Helicobacter spp. are associated with chronic hepatobiliary diseases.

Purpose

We aimed at understanding the microbial etiology in a patient with X-linked agammaglobulinemia presenting with suppurative cholangitis.

Methods

16S rDNA PCR directly performed on a liver biopsy retrieved DNA of H. bilis.

Results

Clinical outcome resulted in the normalization of clinical and biological parameters under antibiotic treatment by a combination of ceftriaxone, metronidazole, and doxycyclin followed by a 2-week treatment with moxifloxacin and a 2-month treatment with azithromycin.

Conclusion

In conclusion, these data suggest a specific clinical and microbiological approach in patients with humoral deficiency in order to detect H. bilis hepatobiliary diseases.
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5.

Background

Millions of people share a bed with their partner. Sleep und relationship could possibly influence each other.

Objectives

To identify and discuss connections between relationship and sleep quality.

Methods

Review of the literature in electronic databases.

Results

Conflict and violence in relationships lead to decreases in both partners’ sleep quality. Constructive approaches to resolving conflicts is necessary for good sleep, and vice versa. Women prefer partners with sleep-wake rhythms matching their own and report higher relationship satisfactions when the couple’s chronotypes are compatible.

Conclusions

Sleep and circadian rhythms play important roles in relationships. When treating insomnia, the relationship and the partner’s sleep should be taken into account.
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6.

Background

Turkey, with a Muslim population of officially over 99 %, is one of the few secular states in the Muslim world. Although state institutions are not based on Islamic juridical and ethical norms, the latter play a significant role in defining people’s attitudes towards controversial issues in the modern world, especially when backed by opinions of Muslim scholars living in Turkey. Accordingly, opinions of Muslim scholars undoubtedly have an important effect on bioethical decisions made by institutions and individuals.

Objective(s)

To explore the ethical positions of Muslim scholars living in Turkey and their arguments used in the ethical assessment of embryonic stem cell research; to discuss the biological-moral tensions arising in medical research on human embryos.

Design

Qualitative study.

Setting

Muslim scholars located in different parts of Turkey.

Methods

Qualitative method, involving the collection of opinions of various scholars, by means of 15 individual semi-structured interviews, evaluated using thematic qualitative analysis.

Results

Positions regarding embryonic stem cell research differ among Muslim scholars in Turkey. On the other hand, even where positions are similar, they are often supported by different arguments.

Conclusion

Despite the heterogeneity of the arguments presented, the dominant position considers embryonic stem cell research as morally acceptable.
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7.

Objective

RBL-2H3 cells express Toll-like receptors, including TLR4. This study aims to assess various aspects of the TLR4 pathway.

Methods

RBL-2H3 cells were indirectly stained for cell surface TLR4, 25 CD14 and intracellular MyD88 proteins and analysed through flow cytometry for single-colour staining.

Results

While TLR4-receptors are expressed in RBL-2H3 cells, associated elements involved in the signaling pathway, CD14 and MyD88, are not.

Conclusion

Care should be taken if RBL-2H3 cells are used to study aspects of the innate immune system in mast cells.
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8.

Background

Trichothiodystrophy nonphotosensitive 1 (TTDN1) is a disease with mental retardation, brittle hair. Some cases of the diseases are caused by mutations of the MPLKIP gene.

Methods

We carefully identified the clinic characteristics, the sulfur level and pattern of the hair shafts of a female patient of with the symptom of hypergonadotropic hypogonadism, and of her parents and brother whose are healthy. We also collected the blood sample of the patient and performed the exon sequencing. One G insertion in MPLKIP was identified after analyzing the obtained exon sequencing profile. The G insertion sites in the patient, her parents and brother, were verified using Sanger sequencing. The G insertion in MPLKIP were compared to the dbSNP.

Results

The female patient of TTDN1 carries a homozygous G insertion (rs747470385) in the MPLKIP gene. The parents and brother of the patient are heterozygous carriers of the same mutation, but are healthy. The hair shafts of the patient had a tiger-tail pattern with relatively low sulfur levels. To the best of our knowledge, this is the first report that autosomal recessive inheritance of the G insertion in the MPLKIP gene results in TTDN1.

Conclusion

Our results indicate that the homozygotic G insertion in MPLKIP results in the TTDN1 with hypergonadotropic hypogonadism, while heterozygous carriers of the same mutation have no symptoms and healthy. These results provide novel insights into the association of mutations in MPLKIP and TTDN1 with hypergonadotropic hypogonadism.
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9.

Objective and design

Temporomandibular disorder (TMD) is a common painful condition in the temporomandibular joint (TMJ). Joint inflammation is believed to be a chief cause of pain in patients with TMD, through the release of pro-inflammatory cytokines that induce peripheral sensitization of nerve terminals followed by microglial stimulation.

Materials and subject

TMJ was induced in rats with the injection of complete Freund’s adjuvant (CFA) emulsion into the left TMJ capsule.

Treatment

The present study would assess the effects of micronized palmitoylethanolamide (m-PEA) on glial activation and trigeminal hypersensitivity.

Methods

Ten mg/kg m-PEA or corresponding vehicle was administered 1 h after CFA and mechanical allodynia and edema were evaluated at 24 and 72 h after CFA injection.

Results

CFA-injected animals showed TMJ edema and ipsilateral mechanical allodynia accompanied by a robust growth in GFAP protein-positive satellite glial cells and activation of resident macrophages in the TG. Moreover, m-PEA administration significantly reduced the degree of TMJ damage and pain, macrophage activation in TG and up-regulation of Iba1.

Conclusions

The results confirm that m-PEA could represent a novel approach for monitoring pain during trigeminal nerve sensitization.
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10.

Background

Studies have shown that sleep quality is negatively affected by perfectionism. Moreover, partner- or relationship-oriented perfectionism negatively influences relationship quality.

Objective

This paper aims to investigate the association of general perfectionism with sleep quality and relationship quality.

Materials and methods

A study assessing perfectionism, sleep quality, and relationship quality was performed via analyzing online questionnaires completed by 489 German adults from the general population.

Results

Participants with impaired sleep showed a higher level of maladaptive perfectionism (concern over mistakes and doubts, parental expectations, and criticism) than participants with good sleep, whereby the severity of sleep problems was not determining. Relationship quality is affected by perfectionism. However, this association is mediated by sleep quality.

Conclusion

Perfectionism is associated with worse sleep quality but not with worse relationship quality when sleep quality is integrated into the model as a mediator.
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11.
12.

Objective

To evaluate the evidence regarding the disease concept of histamine intolerance as a state of inadequate histamine inactivation.

Methods

Keyword-based systematic screening of the scientific literature and of public websites focusing on diagnostic and therapeutic procedures.

Results

Histamine intolerance is commonly diagnosed based solely on subjective reporting of symptoms instead of following systematic diagnostic procedures based on objective laboratory and physical parameters. The only effective long-term therapy is avoidance of histamine-containing food.

Conclusions

The concept of histamine intolerance as a metabolic disease is in need of more experimental and clinical evidence and affected patients will benefit from a clear, evidence-based diagnostic and therapeutic regime.
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13.

Purpose

To investigate the incidence and anatomical location of mandibular nutrient canals (NCs) originating from the mandibular canal using dental cone beam computed tomography (CBCT).

Methods

CBCT images from 105 patients were examined to evaluate the presence, number, diameter, and course of NCs.

Results

NCs and their foramina were bilaterally located in 17 (16.2 %) images. The mean diameters of NCs and foramina were 0.9 ± 0.4 (range, 0.2–3.2) mm and 0.9 ± 0.4 (0.2–2.1) mm, respectively. NCs coursed through the mandibular incisor region up to the lingual surface of the alveolar bone crest.

Conclusion

The present study revealed the frequency and distribution of NCs using CBCT image analysis. NCs are important because surgical injury to the neurovascular bundle within these canals can lead to excessive bleeding and postoperative paresthesia. The identification of NC on CBCT images may be useful during the harvesting of bone blocks or placement of endosseous implants in the anterior region of the mandible.
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14.

Objective and design

The aim of this study was to investigate the contribution of IL-33/ST2 axis in the onset and progression of acute liver injury using a mice model of drug-induced liver injury (DILI).

Material and treatments

DILI was induced by overdose administration of acetaminophen (APAP) by oral gavage in wild-type BALB/c, ST2-deficient mice and in different bone marrow chimeras. Neutrophils were depleted by anti-Ly6G and macrophages with clodronate liposomes (CLL).

Methods

Blood and liver were collected for biochemical, immunologic and genetic analyses. Mice were imaged by confocal intravital microscopy and liver non-parenchymal cells and hepatocytes were isolated for flow cytometry, genetic and immunofluorescence studies.

Results

Acetaminophen overdose caused a massive necrosis and accumulation of immune cells within the liver, concomitantly with IL-33 and chemokine release. Liver non-parenchymal cells were the major sensors for IL-33, and amongst them, neutrophils were the major players in amplification of the inflammatory response triggered by IL-33/ST2 signalling pathway.

Conclusion

Blockage of IL-33/ST2 axis reduces APAP-mediated organ injury by dampening liver chemokine release and activation of resident and infiltrating liver non-parenchymal cells.
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15.

Background

SNOMED CT is the most comprehensive medical terminology. However, its use for intelligent services based on formal reasoning is questionable.

Methods

The analysis of the structure of SNOMED CT is based on the formal top-level ontology DOLCE.

Results

The analysis revealed several ontological and knowledge-engineering errors, the most important are errors in the hierarchy (mostly from an ontological point of view, but also regarding medical aspects) and the mixing of subsumption relations with other types (mostly 'part of').

Conclusion

The found errors impede formal reasoning. The paper presents a possible way to correct these problems.
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16.

Purpose

For the past few years, anterior exposure for surgery of the lumbar spine has gained popularity for the treatment of disk disease or spondylosis. Cancellous bone remains the gold standard for fusion. Iliac crest bone harvesting is safe but there are donor site complications. Bone substitutes exist, like recombinant human bone morphogenic protein-2 rhBMP-2. This alternative offers a high rate of fusion but with local and general complications. The aim of our study is to show the feasibility of an endopelvic approach for iliac bone crest harvesting to avoid donor site complication.

Method

Twenty anterior retroperitoneal lumbar spine approaches have been realized in the anatomy department of the University of Bordeaux. The volumes of cancellous bone have been measured and procedure complications have been reported.

Results

The mean volume of cancellous bone was 5.9 cc, the maximum volume was 8.2 cc and the minimum volume was 4.5 cc. No complications have been reported during the approach or the bone harvesting.

Conclusions

Anterior retroperitoneal approach for iliac bone crest harvesting is a safe way to obtain sufficient volume of cancellous bone for a single lumbar spinal fusion. This exposure avoids the risks of an iliac crest donor site complications or rhBMP-2 complications.
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17.

Background

Hypohidrotic ectodermal dysplasia (HED) is a common recessive X-linked hereditary disease that affects the development of ectoderm. Gene mutations of ectodysplasin A (EDA) play key roles in process of this disease. In our preliminary study, three unknown mutation sites (c.878?T?>?G, c.663-697del and c.587-615del) were detected from the pedigrees of HED.

Methods

Conservation analysis of the related homologous proteins in 3 unknown EDA gene mutation sites was conducted using the University of California Santa Cruz (UCSC) Genome Browser database. SIFT and PolyPhen-2, the online gene function prediction software, were utilized to predict the pathogenicity of point mutation of c.878?T?>?G.

Results

All three unknown mutation sites were located in the highly-conserved region of EDA and possessed strong amino acid conservation among different species. In addition, the results of the pathogenicity prediction of point mutation of c.878?T?>?G by SIFT (P?=?0.00) and PolyPhen-2 (S?=?0.997) demonstrated that the mutation site had considerable pathogenicity theoretically.

Conclusions

The EDA mutations of c.878?T?>?G, c.663-697del and c.587-615del may be responsible for the pathogenesis of HED in their pedigrees.
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18.
19.

Background

There are currently limited pathways into a career in health policy research in Australia, due in part to a serious absence of health policy research capability in Australian universities.

Discussion

We define what we consider health policy research and education should comprise. We then examine what is currently on offer and propose ways to strengthen health policy research in Australia.

Summary

This paper, which is part analysis and part commentary, is offered to provoke wider debate about how health policy research can be nurtured in Australia.
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20.

Objective and design

Evaluating the pro-/anti-inflammatory activity of the C-terminal cleavage product of osteopontin in comparison to angiotensin 1–7.

Material and subjects

Human coronary endothelial cells (hcEC) treated with conditioned media from human U937 macrophages.

Treatment

Macrophages were (pre)treated with C-terminal, full-length or N-terminal osteopontin (OPN-C, OPN-FL, OPN-N, respectively), angiotensin II, angiotensin 1–7 or TNF-α. OPN-C modulatory capacity was compared to that of Ang1–7 in inhibiting subsequent Ag II, OPN-FL or OPN-N-induced macrophage-mediated endothelial inflammation.

Methods

Protein expression of NFκB, IκB, vCAM-1 and iCAM-1 was assessed using western blot. Promotor activation by NFκB was also assessed by dual-luciferase reporter assay.

Results

Conditioned media of macrophages treated with OPN-C induced hcECs’ NfκB activation to a lower degree than OPN-FL or OPN-N. Priming of macrophages with angiotensin 1–7 attenuated the endothelial pro-inflammatory effect induced by subsequent exposure of the macrophages to angiotensin II, OPN-FL or OPN-N. This was evidenced by both NfκB activation and vCAM and iCAM expression. In contrast, priming macrophages with OPN-C did not significantly attenuate the subsequent response to the pro-inflammatory cytokines.

Conclusions

OPN-C induces lower macrophage-induced endothelial inflammation compared to OPN-FL or OPN-N, but unlike angiotensin 1–7, fails to prevent endothelial inflammation induced by subsequent pro-inflammatory macrophage stimulation.
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