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Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme for nicotinamide adenine dinucleotide (NAD) synthesis and is involved in cancer cell proliferation through regulation of energy production pathways. Therefore, NAMPT inhibitors are promising drugs for cancer therapy by limiting energy supply of tumours. Herein, we demonstrated that the NAMPT inhibitor FK866 ((E)-N-(4-(1-Benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide) dose-dependently inhibited growth and cell motility of DU-145 prostate tumour spheroids and decreased the intracellular ATP concentration. The apoptosis marker cleaved caspase-3 remained unchanged, but the autophagy marker microtubule-associated protein 1A/1B-light chain 3 (LC3) was upregulated. Growth inhibition was reversed upon co-administration of NAD to the cell culture medium. FK866 decreased calcein as well as pheophorbide A efflux from tumour spheroids and increased doxorubicin toxicity, indicating interference with function of drug efflux transporters. DU-145 multicellular tumour spheroids expressed the stem cell associated markers CD133, CD44, Oct4, Nanog, Sox2, and drug transporters ABCB1, ABCG2, and ABCC1 which are associated with stem cell properties in cancer cells. The ABCB1 inhibitor zosuquidar, the ABCG2 inhibitor Ko143, and the ABCC1 inhibitor MK571 increased calcein retention. Neither protein expression of stem cell markers, nor drug transporters was significantly changed upon FK866 treatment. In conclusion, our data suggest that FK866 inhibits prostate cancer cell proliferation by interference with the energy metabolism, and function of drug efflux transporters., (© 2020 The Authors. Clinical and Experimental Pharmacology and Physiology published by John Wiley & Sons Australia, Ltd.)

Background: Diced cartilage in fascia has become the graft material of choice for dorsal grafts in rhinoplasty. Allogenic fascia lata has not yet been investigated as an isolated fascial graft or as a combined graft with ear and rib cartilage, especially in comparison with autologous fascia and over a long implantation period., Methods: Ten different grafts were built from either autologous or allogenic fascia lata alone or as diced cartilage in fascia grafts with diced costal or ear cartilage and implanted into the dorsal skin of 15 rabbits. After 3 or 9 months, the grafts were explanted and analyzed histologically. Chondrocytes and cartilage matrix characteristics, including calcification, ossification, formation of bone marrow, fibrosis ingrowth and fibrotic transformation, the presence of immune reactions, vascular ingrowth, regenerative capacity, and capsule formation, were examined in a semiquantitative manner., Results: All grafts were vital and without inflammatory response. The cartilage showed regular nuclei, a normal matrix, and regenerative capacity. A higher grade of calcification and ossification was observed in the fascia/cartilage grafts than in isolated cartilage grafts, and was more pronounced for costal cartilage. Both types of fascia were shown to be equally stable and without degradation. There were no significant differences in the diced cartilage in fascia grafts built with autologous compared to allogenic fascia., Conclusions: This study shows the equivalency of diced cartilage in fascia grafts and isolated fascial grafts using allogenic fascia lata compared to autologous fascia. The type of cartilage used accounts for different long-term characteristics of diced cartilage in fascia grafts.

Childhood autism or autism spectrum disorder (ASD) has been regarded as one of the most stable diagnostic categories applied to young children with psychiatric/developmental disorders. The stability over time of a diagnosis of ASD is theoretically interesting and important for various diagnostic and clinical reasons. We studied the diagnostic stability of ASD from childhood to early adulthood in the Faroe Islands: a total school age population sample (8-17-year-olds) was screened and diagnostically assessed for AD in 2002 and 2009. This paper compares both independent clinical diagnosis and Diagnostic Interview for Social and Communication Disorders (DISCO) algorithm diagnosis at two time points, separated by seven years. The stability of clinical ASD diagnosis was perfect for AD, good for "atypical autism"/PDD-NOS, and less than perfect for Asperger syndrome (AS). Stability of the DISCO algorithm subcategory diagnoses was more variable but still good for AD. Both systems showed excellent stability over the seven-year period for "any ASD" diagnosis, although a number of clear cases had been missed at the original screening in 2002. The findings support the notion that subcategories of ASD should be collapsed into one overarching diagnostic entity with subgrouping achieved on other "non-autism" variables, such as IQ and language levels and overall adaptive functioning.

We have followed up a 2002 population study of autism prevalence in 15-24-year olds in the Faroe Islands. The rate of ASD grew significantly from 0.56% in 2002 to 0.94% in 2009. Although these results are within the range of typical findings from other studies, there were some interesting details. There were-in addition to 43 originally diagnosed cases in 2002-24 newly discovered cases in 2009 and nearly half of them were females. It is possible that unfamiliarity with the clinical presentation of autism in females have played a significant role in this context. There was diagnostic stability for the overall category of ASD over time in the group diagnosed in childhood (7-16) years, but considerable variability as regards diagnostic sub-groupings.

The prevalence of food allergies still continues to rise in western Europe. As the strict avoidance of food allergens represents a major issue in the management of this disease, information for consumers on food labels about allergenic ingredients is crucial. The European labelling law for foodstuffs excludes declarations of the ingredients on individually wrapped foodstuffs with outer packages and products whose largest single surface area falls below 10 cm(2). One potentially avoidable case, with fatal consequences due to this law and the current legal situation, is discussed herein. We suggest evaluating the benefits of a mandatory safety warning (symbol) for major allergenic food ingredients on every foodstuff package, without any exceptions based on the size of the product or the presence of secondary packages., (Copyright 2008 S. Karger AG, Basel.)

The Faroe Islands are considered to be a genetic isolate. This population study of the prevalence of autism sought to identify a representative cohort for future genetic studies. In 2002 all schools were screened for autism spectrum disorders. The target population were all children born in 1985 through 1994 and living in the Faroe Islands on December 31, 2002. Children who screened positive for autism characteristics were examined using the Diagnostic Interview for Social and Communication Disorders (DISCO). Of the children aged 8 through 17 years, 0.56% had childhood autism, Asperger syndrome or atypical autism. The male:female ratio was just under 6:1. The prevalence of autism in the Faroe Islands was very similar to that reported from many western countries.

So far no national or regional studies have been published in Germany regarding the number of fatal aviation accidents and results of autopsy findings. Therefore, we evaluated all fatal aviation accidents occurring in Lower Saxony from 1979 to 1996. A total of 96 aviation accidents occurred in this period involving 73 aeroplanes. The crashes resulted in the death of 154 people ranging in age from 19 to 68 years. The greatest number of victims in a single crash of an aircraft was (n=7). Other types of fatal accidents were crashes of aircraft and helicopter while on the ground (n=5), hot-air balloons (n=2), parachutes (n=10), hang glider accidents (n=5) and the striking of a bystander by a model airplane. Autopsies were performed on 68 of the 154 victims (44.2%), including 39 of the 73 pilots (53.4%). Some of the autopsies yielded findings relevant to the cause of the accident: gunshot wounds, the presence of alcohol or drugs in blood and preexisting diseases. Our findings emphasize the need for autopsy on all aviation accident victims, especially pilots, as this is the only reliable method to uncover all factors contributing to an accident.

Authors report on two cases of homicide and another case of suicide, all committed with captive-bolt livestock-stunners. The investigation of skull caps revealed roundish holes at the entry sites which were beveled-out in a paraboloid-like manner on the inner aspect. These defects were reproducible in test shots with various strengths of ammunition and different materials as targets.

Unlabelled: Up to now reliable data were available on cases of lethal child neglect in the area of the Federal Republic of Germany prior to reunification (the former West Germany). In a multicenter study we therefore examined the police and court records for such cases occurring in the period from 1 January 1985 to 2 October 1990 in nearly the entire area of Federal Republic of Germany., Results: The study center received information on 19 cases of lethal child neglect. Extrapolated to all institutes of legal medicine, this corresponds to 20 cases and thus 3.5 cases a year in the whole of West Germany in the period studied. There is to be added a dark-field which cannot be limited more precisely. However, the cases of fatal child neglect might have occurred much more seldom than fatal child abuse caused by use of physical violence. Slightly more than half the victims were younger than 1 year, the oldest one was 7 10/12 years old. Most frequently the children died of starvation and thirst. Mostly the mothers/nursing mothers killed the child alone or together with the victim's father/stepfather. In the majority of the cases there was not a close affection between parents and child. Nearly 30% female/male perpetrators suffered from chronic alcohol abuse. Only 15 (= 56%) of 27 female/male perpetrators were sentenced to imprisonment (period between 7 months on probation and 10 years). Mitigation circumstances existed for nearly half the persons sentenced to imprisonment. It is true that child neglect is a rarer crime, but the experts of legal medicine always have to indicate errors made during the external inspection of the corpse (among others failures to see indications of neglect).

Unlabelled: No reliable data are available on cases of lethal child abuse (by active force) in the area of Federal Republic of Germany prior to reunification (the former West Germany). In a multicenter study we therefore examined the police and court records for such cases occurring in the period 1 January 1985 to 2 October 1990 in nearly the entire area of Federal Republic of Germany., Results: The study center received information on 58 cases of lethal child abuse. Extrapolated to all institutes of legal medicine, this corresponds to 62 cases in all of West Germany in the period studied. An approximately equal number of unreported cases should be added to this figure. Including unreported cases, at least 20 cases of lethal child abuse occurred per year; thus only one in every two cases ever came to light. Almost two thirds of the victims were younger than one year old. At autopsy 59% exhibited signs of repeated abuse at autopsy. By far the most common cause of death was direct impact from a blunt object, usually to the head. Mostly, the male person to whom the victim relates most closely (father, stepfather, partner of the mother) has killed the child. Twenty-one of the 74 persons charged saw the charges against them dropped or were acquitted due to lack of evidence; 51 received sentences ranging from one year probation to life. In the remaining two cases the outcome of the trial was unknown. Signs of abuse were readily apparent at autopsy in almost all cases. The high number of unreported cases underscores the need to educate medical students and practicing physicians to be on the look-out for signs of abuse and argues for an increase in the rate of autopsy.

Based on the description of the findings of four cases of self-strangulation with multiple knotting of the strangling device examined by the authors general criminological and specific forensic criteria for differential diagnosis of suicide and commission of the offence by another person are discussed. Though multiple knotting of the strangling device, caught hair and parts of clothes and concomitant injuries may also be seen in cases of suicide, they primarily justify the suspicion that the death was caused by another person. If it is one of those rare cases of self-strangulation with multiple knotting, the presence of symptoms of congestion in the head area, which may occasionally be absent in other cases of strangulation, is necessary for pathophysiological reasons.

The early phase of wound repair after liver incisions was investigated by histological, enzyme-histochemical, and biochemical methods in guinea pigs. There are considerable differences in cellular and histochemical reactions in comparison to incisions of the skin: 1. The rapid leukocytic reaction showed little change during the observation interval (48 h). In short survival times epithelial cells show signs of hypoxidosis and loss of glycogen at the edge of an incision. Proliferation of organ-specific and mesenchymal cells was observed after more than 24 h. 2. Alterations of the investigated enzymes in the traumatic area are important diagnostic parameters in the early stages of wound healing. 3. In the early 12 h after injury distinct increase of histamine was observed, while serotonin was noticed to decrease. 4. Therefore, the determination of wound age in the early wound reactions after injuries of the liver should include enzymehistochemical methods.

It is reported about a female patient with two lipomas of the liver. The special diagnosis and the differentiation against metastases and other malignant tumors of the liver are only possible by means of computertomography. Scintigraphy and sonography do not allow a differential diagnosis. On the one hand lipoma of the liver is a very rare and benign disease but on the other hand a correct diagnosis may be - like in this case - very important because of therapy and prognosis.

Camera-Kinematography is a nearly noninvasive method to investigate regional motion of the myocard, and allows evaluation of the function of the heart. About 20 min after injection of 15-20 mCi of 99mTC-Human-Serum-Albumin, when the tracer is distributed homogenously within the bloodpool, data acquisition starts. Myocardial wall motion is represented in an appropriate quasi three-dimensional form. In this representation scars can be revealed as "silent" (akinetic) regions, aneurysms by asynchronic motion. Time activity curves for arbitrarily chosen regions can be calculated and give an equivalent for regional volume changes. 16 patients with an old infarction have been investigated. In fourteen cases the location and extent of regions with abnormal motion could be evaluated. Only two cases of a small posterior wall infarction did not show deviations from normal contraction pattern.

First clinical results of patients with diseases of the lungs. The previous experiences on patients with diseases of the lungs reveal that the regional function diagnostics of the lungs may be extended and improved by functional scintigraphic radiospirometry. Because of the determination of regional lung volumes restrictive lung diseases can be differentiated and analysed more exactly than it has been possible before by the examinations of perfusion and ventilation alone. A further advance of the determination of lung volume is that the question of functional operability can be cleared up exactly. In our opinion the routine use of the functional scintigraphic radiospirometry is justified. A contraindication for this kind of examination should only be pregnancy.

The diagnostic accuracy of CT in cases of lumbar disk prolapse was investigated on the basis of a group of 158 of our own patients who were divided into three separate groups. CT findings were compared on the one hand with myelograms and on the other with results of surgery. Simultaneously performed myelographic and CT examinations produced different diagnostic findings in 7 out of 80 lumbar disks (approx. 9%). These deviating findings ranged from gradual differences (in 3 cases) to completely contradictory findings (in 4 cases). In 31 patients who underwent surgery, approximately the same amount of false-positive and false-negative findings were obtained in preoperative diagnosis using CT as with myelography. The overall accuracy calculated for non-invasive computerized tomography was 93.7%, while for myelography it was 90.7%. Out of a further 91 patients in whom myelography was not performed and whose condition was checked surgically, the diagnosis had been established correctly by CT in 88. This represents a degree of accuracy of 96%. The vertical and lateral location of the disk prolapses as determined by CT corresponded with findings at surgery in every case. It is concluded from the results of these investigations that CT should be given absolute priority over myelography in the diagnosis of lumbar disk prolapse and that if there is a correlation between clinical history, neurological deficiency symptoms, and CT findings, myelography is unnecessary, even for surgery. Only if there are discrepancies between the findings myelography is indicated as a supplementary examination. CT and myelography are examination methods which complement, rather than complete with one another.