It is well accepted that the Americas were the last continents reached by modern humans, most likely through Beringia. However, the precise time and mode of the colonization of the New World remain ...hotly disputed issues. Native American populations exhibit almost exclusively five mitochondrial DNA (mtDNA) haplogroups (A–D and X). Haplogroups A–D are also frequent in Asia, suggesting a northeastern Asian origin of these lineages. However, the differential pattern of distribution and frequency of haplogroup X led some to suggest that it may represent an independent migration to the Americas. Here we show, by using 86 complete mitochondrial genomes, that all Native American haplogroups, including haplogroup X, were part of a single founding population, thereby refuting multiple-migration models. A detailed demographic history of the mtDNA sequences estimated with a Bayesian coalescent method indicates a complex model for the peopling of the Americas, in which the initial differentiation from Asian populations ended with a moderate bottleneck in Beringia during the last glacial maximum (LGM), around ∼23,000 to ∼19,000 years ago. Toward the end of the LGM, a strong population expansion started ∼18,000 and finished ∼15,000 years ago. These results support a pre-Clovis occupation of the New World, suggesting a rapid settlement of the continent along a Pacific coastal route.
Malignant tumors of the skin had been a rare entity 2 decades ago. Today they are spread rapidly worldwide. Malignant neoplasms of the skin, the largest human organ, may occur from all structures and ...layers. While previously skin cancer -occurred mainly after the age of 60, the incidence increases now in younger ages. Strong sunburns in the childhood and before the age of 20 are important risk factors for the development of malignancies of the skin. An increased exposure to UV rays is found especially in the facial skin, where basal cell carcinoma, squamous cell carcinoma, malignant melanoma and Merkel cell carcinomas are the most common malignancies. Early diagnosis of malignancies and therapy-oriented mostly surgical approaches are crucial for the prognosis of all skin cancers. Therefore under the aspect of the increasing incidence these topics will be pointed out according to the latest findings including current multimodal therapy concepts and future treatment options.
Summary Bisphosphonates are used as potent inhibitors in metastatic bone lesions. They can reduce skeletal burden and prevent bony metastases. They are integral in the treatment of some tumours like ...breast cancer, prostate cancer and multiple myeloma. As a side effect, these drugs also may cause severe jaw necrosis. Twenty-four patients with bisphosphonate-related jaw necrosis were analyzed in a clinical study. These necroses mostly appeared after administration of aminobisphosphonates. Recurrent avascular necroses were found after changing from Pramidronate to Zoledronate. All patients were treated by resection of necrotic bone. Repeated surgical interventions were required with about 25% of the patients. The management of patients with bisphosphonate-related jaw necrosis remains extremely difficult and includes surgical procedures as well as the eradicating of the necrotic bone including antibiotic therapy. The prevention of such complications consists in a minimization of dental surgical interventions and an avoidance of ulcers by dental prosthesis.
Eagle's syndrome is caused by an elongated or mineralised styloid process and characterised by facial and pharyngeal pain, odynophagia and dysphagia. Diagnosis is based on clinical findings. However ...radiologic imaging, like panoramic radiograph, helps to confirm the diagnosis. There are different treatments of the Eagle's syndrome. Anti-inflammatory medication (carbamazepime, corticosteroids) and/or surgical interventions are established. The aim of the different surgical techniques is to resect the elongated styloid process near the skull base.
A transoral, retromolar, para-tonsillar approach was performed to expose and resect the elongated calcified styloid process in a consecutive series of six patients. The use of different angled ring curettes, generally used in hypophysis surgery, facilitated the preparation of the styloid process through the surrounding tissue to the skull base, without a compromise to the surrounding tissue. Clinical examinations were performed pre- and postoperatively (3 month and after 1 year after surgery) in all patients.
No intra- or postoperative complications were observed. The hypophysis ring curettes facilitated the preparation of the styloid process to the skull base.
The transoral, retromolar, para-tonsillar approach is a secure and fast method to resect an elongated symptomatic styloid process. Side effects of the classical transoral trans-tonsillar approach did not occur.
The spatial distribution of the sodium ions in sodium rubidium borate glasses with composition (Na2O)x(Rb2O)1−xy(B2O3)1−y (0⩽x⩽1, y=0.2 and 0.3) has been studied by complementary high resolution and ...dipolar solid state NMR experiments. 11B{23Na} rotational echo double resonance (REDOR) measurements indicate that the trigonal BO3/2 groups and the four-coordinate BO4/2- units experience 23Na local dipolar fields of similar magnitudes, consistent with a random distribution of the overall cation population. Combined with this result, 23Na–23Na homonuclear second moments measured via 23Na spin echo decay spectroscopy reveal non-statistical mixing of sodium and rubidium ions in relation to each other, suggesting some preference of like-cation interactions. These results support the idea that the details of unlike-cation mixing are influenced by the size differences between the ions involved.
We have investigated the dynamics in polycrystalline samples of l-methionine related to the structural transition at about 307K by incoherent inelastic and quasielastic neutron scattering, X-ray ...powder diffraction as well as ab-initio calculations. l-Methionine is a sulfur amino acid which can be considered a derivative of alanine with the alanine R-group CH3 exchanged by CH3S(CH2)2. Using X-ray powder diffraction we have observed at ~190K an anomalous drop of the c-lattice parameter and an abrupt change of the β-monoclinic angle that could be correlated to the anomalies observed in previous specific heat measurements. Distinct changes in the quasielastic region of the neutron spectra are interpreted as being due to the onset and slowing-down of reorientational motions of the CH3–S group, are clearly distinguished above 130K in crystalline l-methionine. Large-amplitude motions observed at low frequencies are also activated above 275K, while other well-defined vibrations are damped. The ensemble of our results suggests that the crystalline structure of l-methionine is dynamically highly disordered above 275K, and such disorder can be linked to the flexibility of the molecular thiol-ether group.
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•l-Methionine has a dynamically disordered structure at room temperature connected to the flexibility of the thiol-ether group.•It undergoes a structural phase transition at body temperature.•The room temperature structure is only recovered after 15min of relaxation time upon warming.•Reorientational dynamics of the methyl group appear as precursor to conformational changes in l-methionine.
To determine whether mental illness is associated with accessibility and remoteness.
A cross-sectional, population-based, computer-assisted telephone interview survey, stratified by Accessibility and ...Remoteness Index of Australia (ARIA) categories.
Secondary analysis of data collected from 2545 South Australian adults in October and November 2000.
Psychological distress and depression as determined by the Kessler 10 Psychological Distress Scale, the SF-12 measure of health status, and self-reported mental illness diagnosed by a doctor in the previous 12 months.
Overall, mental illness prevalence estimates were similar using the three measures of psychological distress (10.5%), clinical depression (12.9%) and self-reported mental health problem (12.7%). For each measure, there was no statistically significant variation in prevalence across ARIA categories, except for a lower than expected prevalence of depression (7.7%) in the "accessible" category. There was no trend suggesting higher levels of mental illness among residents of rural and remote regions.
The prevalence rates of psychological distress, depression and self-reported mental illness are high. However, we found no evidence that the prevalence of these conditions varies substantially across ARIA categories in South Australia. This finding may challenge existing stereotypes about higher levels of mental illness outside metropolitan Australia.
As an integrator of multiple nociceptive and/or inflammatory stimuli, TRPV1 is an attractive therapeutic target for the treatment of various painful disorders. Several TRPV1 antagonists have been ...advanced into clinical trials and the initial observations suggest that TRPV1 antagonism may be associated with mild hyperthermia and thermal insensitivity in man. However, no clinical efficacy studies have been described to date, making an assessment of risk:benefit impossible. Furthermore, it is not clear whether these early observations are representative of all TRPV1 antagonists and whether additional clinical studies with novel TRPV1 antagonists are required in order to understand optimal compound characteristics. In the present study we describe 2-(2,6-dichloro-benzyl)-thiazolo5,4-
dpyrimidin-7-yl-(4-trifluoromethyl-phenyl)-amine (JNJ-39729309) as a novel, TRPV1 antagonist. JNJ-39729209 displaced tritiated resiniferotoxin binding to TRPV1 and prevented TRPV1 activation by capsaicin, protons and heat. In-vivo, JNJ-39729209 blocked capsaicin-induced hypotension, induced a mild hyperthermia and inhibited capsaicin-induced hypothermia in a dose dependent manner. JNJ-39729209 showed significant efficacy against carrageenan- and CFA-evoked thermal hyperalgesia and exhibited significant anti-tussive activity in a guinea-pig model of capsaicin-induced cough. In pharmacokinetic studies, JNJ-39729209 was found to have low clearance, a moderate volume of distribution, good oral bioavailability and was brain penetrant. On the basis of these findings, JNJ-39729209 represents a structurally novel TRPV1 antagonist with potential for clinical development. The advancement of JNJ-39729209 into human clinical trials could be useful in further understanding the analgesic potential of TRPV1 antagonists.
The ability to predict cancer progression may help the clinical management of patients with penile squamous cell carcinoma. We studied 22 cases of squamous cell carcinoma of the penis diagnosed ...between 1989 and 1998. The depth of invasion was measured from the basement membrane of the squamous epithelium to the deepest invasive cancer cells. Cancer progression was defined as the development of lymph node metastasis or distant metastasis. The mean patient age was 63 years and the mean follow-up was 28 months. Ten patients developed cancer progression. The mean depth of invasion among patients with cancer progression was 9.8 mm, as compared to the mean depth of invasion of 4.0 mm among those patients without cancer progression (P = .02). Vascular invasion was also predictive of cancer progression (P = .02). Metastases developed in the majority (6 out of 7) of cases invading more than 6 mm, but developed only in a minority (4 out of 15) of cases invading 6 mm or less. We conclude that depth of invasion and vascular invasion are significant predictors of cancer progression for penile squamous cell carcinoma.
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