Cholinergic control of morphine‐induced locomotion in rostromedial tegmental nucleus versus ventral tegmental area sites

M5 muscarinic acetylcholine receptors expressed on ventral tegmental dopamine (DA) neurons are needed for opioid activation of DA outputs. Here, the M5 receptor gene was bilaterally transfected into neurons in the ventral tegmental area (VTA) or the adjacent rostromedial tegmental nucleus (RMTg) in mice by means of a Herpes simplex viral vector (HSV) to increase the effect of endogenous acetylcholine. Three days after HSV‐M5 gene infusion in VTA sites, morphine‐induced locomotion more than doubled at two doses, while saline‐induced locomotion was unaffected. When the HSV‐M5 gene was infused into the adjacent RMTg, morphine‐induced locomotion was strongly inhibited. The sharp boundary between these opposing effects was found where tyrosine hydroxylase (TH) and cholinesterase labelling decreases (?4.00 mm posterior to bregma). The same HSV‐M5 gene transfections in M5 knockout mice induced even stronger inhibitory behavioural effects in RMTg but more variability in VTA sites due to stereotypy. The VTA sites where HSV‐M5 increased morphine‐induced locomotion receive direct inputs from many RMTg GAD‐positive neurons, and from pontine ChAT‐positive neurons, as shown by cholera‐toxin B retrograde tracing. Therefore, morphine‐induced locomotion was decreased by M5 receptor gene expression in RMTg GABA neurons that directly inhibit VTA DA neurons. Conversely, enhancing M5 receptor gene expression on VTA DA neurons increased morphine‐induced locomotion via cholinergic inputs.     

Expression analysis and clinical correlation of aquaporin 1 and 4 genes in human hippocampal sclerosis

Mesial temporal sclerosis (MTS) is the most frequent cause of drug resistant symptomatic partial epilepsy. The mechanism and genetic background of this unique pathology are not well understood. Aquaporins (AQP) are regulators of water homeostasis in the brain and are expressed in the human hippocampus. We explored the role of AQP genes in the pathogenetic mechanisms of MTS through an evaluation of gene expression in surgically removed human brain tissue. We analyzed AQP1 and 4 mRNA levels by quantitative real-time polymerase chain reaction and normalized to ABL and cyclophilin genes, followed by immunohistochemistry for AQP4. Relative expressions were calculated according to the delta Ct method and the results were compared using the Mann-Whitney U test. Brain specimens of 23 patients with epilepsy who had undergone surgery for MTS and seven control autopsy specimens were investigated. Clinical findings were concordant with previous studies and 61% of the patients were seizure-free in the postoperative period. AQP1 and 4 gene expression levels did not differ between MTS patients and control groups. Immunofluorescence analysis of AQP4 supported the expression results, showing no difference. Previous studies have reported contradictory results about the expression levels of AQP in MTS. To our knowledge, only one study has suggested upregulation whereas the other indicated downregulation of perivascular AQP4. Our study did not support these findings and may rule out the involvement of AQP in human MTS.     

Computer-assisted analysis contour lines of aesthetic unit for the assessment of lip augmentation

Background

Lip augmentation and changing contour lines have become more popular ways of improving the appearance. However, validated measures of lip fullness for quantification of outcomes are needed; ethnic background and personal goals can optimise outcomes while tailoring lip enhancement treatment to each individual’s anatomy. The aim of this study is to analyse the morphological features of the lip in detail and to clarify the objective parameters in related with the subjective ones regarding the lip augmentation and lip reconstruction.

Methods

Standard photographs of the lips of 200 young Anatolian adults were calculated with linear and angular components. The features of the lower third of the face were analysed with the software program. Linear analyses (heights of the upper lip, the upper vermilion, the lower lip height, the lower vermillion and the chin height) and angular analyses (the upper lip, the lower lip, the apex and Cupid’s bow angles) were measured as reference points. The lip shape was classified into five groups: thin, very thin, medium, full and very full.

Results

The lower third of the face was divided into three segments (Sn–Sto, Sm–Me and Sto–Sm), and the largest portion of the lower face was occupied by the chin and the smallest by the lower lip height in both genders. The upper vermilion height was 8.07?±?1.8 mm in males and 7.08?±?1.5 mm in females. The lower vermilion height was 10.1?±?2.4 mm in males and 9.7?±?1.9 mm in females. The upper lip angle was calculated as 30.3?±?9.6° in males and 24.2?±?6.2°mm in females. The lower lip angle was calculated as 38.3?±?9.7° in males and 36.5?±?6.4° in females. Meanwhile, the angular measurements of Cupid’s bow (i.e., the apex and the central angle of Cupid’s bow) were smaller in men than in women. When the lip was analyzed, the medium and full types in upper and lower lips accounted for substantial fractions in men, whereas medium and thin types were predominant also in women.

Conclusions

With the help of certain software, this research has made possible to define the best cosmetical redesign solution of lip construction and augmentation with a natural appearance for the patient.Level of Evidence: Level III, diagnostic study.

     

Delay in Presentation,Diagnosis, and Treatment for Breast Cancer Patients in Jordan

Breast cancer is the most common cancer, and one of the leading causes of death for females in Jordan and many countries in the world. Studies have shown that delay in symptoms presentation, diagnosis or treatment would result in poor prognosis. There has been no published study from Jordan on delays in patient presentation, delays in diagnosis, or delays in treatment. Therefore, we conducted this study to assess these important quality indicators aiming to improve prognosis for breast cancer patients in Jordan. This project was a cross‐sectional study on female breast cancer patients in Jordan. The total number of participants was 327. The proportion of patients with presentation delay, diagnosis delay, and treatment delay was 32.2%, 49.1%, or 32.4%, respectively. The main reported reasons for delay in presentation were ignorance of the nature of the problem (65.6%), limited/lack of knowledge that symptoms were suggestive of cancer diagnosis (16.7%), and misdiagnosis (16.7%). Predictors of delay and mean time for presentation, diagnosis, and treatment were identified. Our results reveal that breast cancer patients in Jordan are experiencing delays in presentation, diagnosis, and treatment. This could justify the advanced stages at diagnosis and poor outcomes for breast cancer patients in Jordan. We recommend revising the current early detection and down‐staging programs in Jordan.     

Identification of Three Novel and One Known Mutation in the WFS1 Gene in Four Unrelated Turkish Families: The Role of Homozygosity Mapping in the Early Diagnosis

Objective:Bi-allelic mutations in the wolframin gene (WFS1) cause Wolfram syndrome 1 (WS1 or DIDMOAD) characterized by non-autoimmune diabetes mellitus, optic atrophy, diabetes insipidus, sensorineural deafness, urinary tract abnormalities, and neuropsychiatric disorders. Patients presenting with an incomplete phenotype of WS1 were evaluated using homozygosity mapping and subsequent whole-exome sequencing.Methods:Four unrelated consanguineous Turkish families, including seven affected children, and their unaffected parents and siblings were evaluated. Homozygosity mapping was performed, followed by whole-exome sequencing of WFS1. Mutations were classified according to results of “in silico” analyses, protein prediction, and functional consequences.Results:Homozygosity mapping confirmed shared homozygous regions on chromosome 4 (chr4p16.1) between the affected individuals, that was absent in their unaffected siblings. Exome sequencing identified three novel (c.1215T>A, c.554G>A, c.1525_1540dup) and one known (c.1522_1523delTA) mutations in WFS1. All mutations were predicted to cause stop codon leading to early termination of protein synthesis and complete loss-of-function. All patients were found to be homozygous for the change, with parents and other unaffected siblings being carriers.Conclusion:Our study expands the mutation spectrum of WSF1 mutations with three novel mutations. Homozygosity mapping may provide enrichment for molecular genetic analysis and early diagnosis of WS1 patients with incomplete phenotype, particularly in consanguineous pedigrees.     

Gastrointestinal amyloidosis: A focused review

Amyloidosis, a heterogenous group of disorders, is characterized by the extracellular deposition of autologous, insoluble, fibrillar misfolded proteins. These extracellular proteins deposit in tissues aggregated in ß-pleated sheets arranged in an antiparallel fashion and cause distortion to the tissue architecture and function. In the current literature, about 60 heterogeneous amyloidogenic proteins have been identified, out of which 27 have been associated with human disease. Classified as a rare disease, amyloidosis is known to have a wide range of possible etiologies and clinical manifestations. The exact incidence and prevalence of the disease is currently unknown. In both systemic and localized amyloidosis, there is infiltration of the abnormal proteins in the layers of the gastrointestinal (GI) tract or the liver parenchyma. The gold standard test for establishing a diagnosis is tissue biopsy followed by Congo Red staining and apple-green birefringence of the Congo Red-stained deposits under polarized light. However, not all patients may have a positive tissue confirmation of the disease. In these cases additional workup and referral to a gastroenterologist may be warranted. Along with symptomatic management, the treatment for GI amyloidosis consists of observation or localized surgical excision in patients with localized disease, and treatment of the underlying pathology in cases of systemic amyloidosis. In this review of the literature, we describe the subtypes of amyloidosis, with a primary focus on the epidemiology, pathogenesis, clinical features, diagnosis and treatment strategies available for GI amyloidosis.