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Great Basin bristlecone pine (Pinus longaeva D.K. Bailey) presence in the Stansbury Mountains of northcentral Utah has been reported prior to the year 2020, but these reports lack adequate population characterization and the delineation of distinct stands of trees. In summer 2020, we identified and documented the presence of 5 separate stands of bristlecone pine in the Stansbury Mountains. These stands are removed from the nearest bristlecone populations in other mountain ranges by a distance of approximately 120 km; as such, they represent a unique outlier population of the species. We used GPS data to create a geographic information system (GIS) database delineating the 5 stands we identified, and we sampled tree age and size in one of the stands for comparison with other bristlecone pine populations in the Great Basin. We present here 2 hypotheses to explain the occurrence of bristlecone pine in the Stansbury Mountains: first, that this population is a relict from a time when bristlecone pine was widely distributed across the Great Basin; and second, that the species arrived in the range via long-distance dispersal mechanisms at some point during or after the Pleistocene/Holocene transition (ca. 12,000 14C YBP). Neotoma (woodrat) midden data suggest that bristlecone pine was absent or at least not widespread in the northern Bonneville Basin during the late Pleistocene, but midden data are sparse for the Stansbury Mountains and surrounding ranges. Additionally, we present possible migration pathways that the species could have taken to reach the Stansbury Mountains from the southern Bonneville Basin, where it was widespread during the late Pleistocene, using the largest extent of Lake Bonneville as a limiting boundary. Hypothesized migration vectors include windborne long-distance dispersal events or transport by granivorous birds. We also postulate that a small population of bristlecone pine may be present in the Oquirrh Mountains to the east of the Stansbury Mountains based upon the existence of similar habitat characteristics there, as well as our identification of a likely misdetermined 1964 voucher specimen from the Oquirrh Mountains that appears to be of bristlecone pine. [ABSTRACT FROM AUTHOR]

Great Basin bristlecone pine (Pinus longaeva D.K. Bailey) presence in the Stansbury Mountains of northcentral Utah has been reported prior to the year 2020, but these reports lack adequate population characterization and the delineation of distinct stands of trees. In summer 2020, we identified and documented the presence of 5 separate stands of bristlecone pine in the Stansbury Mountains. These stands are removed from the nearest bristlecone populations in other mountain ranges by a distance of approximately 120 km; as such, they represent a unique outlier population of the species. We used GPS data to create a geographic information system (GIS) database delineating the 5 stands we identified, and we sampled tree age and size in one of the stands for comparison with other bristlecone pine populations in the Great Basin. We present here 2 hypotheses to explain the occurrence of bristlecone pine in the Stansbury Mountains: first, that this population is a relict from a time when bristlecone pine was widely distributed across the Great Basin; and second, that the species arrived in the range via long-distance dispersal mechanisms at some point during or after the Pleistocene/Holocene transition (ca. 12,000 14C YBP). Neotoma (woodrat) midden data suggest that bristlecone pine was absent or at least not widespread in the northern Bonneville Basin during the late Pleistocene, but midden data are sparse for the Stansbury Mountains and surrounding ranges. Additionally, we present possible migration pathways that the species could have taken to reach the Stansbury Mountains from the southern Bonneville Basin, where it was widespread during the late Pleistocene, using the largest extent of Lake Bonneville as a limiting boundary. Hypothesized migration vectors include windborne long-distance dispersal events or transport by granivorous birds. We also postulate that a small population of bristlecone pine may be present in the Oquirrh Mountains to the east of the Stansbury Mountains based upon the existence of similar habitat characteristics there, as well as our identification of a likely misdetermined 1964 voucher specimen from the Oquirrh Mountains that appears to be of bristlecone pine. [ABSTRACT FROM AUTHOR]

The article "Cultural Policy" deals with the measures taken by the European Union to support the cultural sector after the effects of the COVID-19 pandemic. UNESCO estimates that worldwide about ten million jobs have been lost in the cultural and creative industries. The European Parliament calls for increased cultural promotion and the inclusion of the cultural and creative industries in financial support instruments. The Slovenian Presidency of the Council focuses on the preservation of European cultural heritage from the perspective of ecological sustainability, while the French Presidency of the Council focuses on the revival of the cultural and creative industries. The European Commission has published guidelines for the safe resumption of activities in the cultural and creative sector and has called on Member States to make use of the Recovery and Resilience Facility for the cultural sector. The financial volume of the Creative Europe cultural promotion program has been increased and measures have been taken to support Member States. The United Kingdom has lost access to ongoing EU programs after Brexit. There are also other programs with a cultural or creative industry focus, such as the New European Bauhaus and the European Agenda for Culture. The European Parliament calls for the fight against racism through art and culture and proposes to strategically include the topic of recovery and resilience of the cultural and creative industry in future work plans. [Extracted from the article]

Objective: To compare the hypoglycemic effect of the aqueous extract of Moringa oleifera (moringa), Smallanthus sonchifolius (yacon) and metformin on Rattus norvegicus, albino variety, with induced diabetes mellitus. Materials and methods: Preclinical, experimental, controlled and randomized study. Diabetes was induced intraperitoneally with a dose of alloxan at 130 mg/kg. A total of 24 male Rattus norvegicus, albino variety, Holfzman strain (6 per group) were used. They were divided as follows: control group (no treatment), metformin group (14 mg/kg), M. oleifera group (200 mg/kg), and S. sonchifolius group (140 mg/kg), treatments were administered via orogastric tube for 15 days. Glycemia levels were determined using an Accu-Chek® Instant electronic glycometer (Roche). Results: Decreased glycemia was observed in the treatment groups: M. oleifera (p = 0.009), S. sonchifolius (p = 0.002) and metformin (p = 0.002), by 313 mg/dL, 281.5 mg/dL and 415 mg/dL, respectively. When comparing glycemia in the treated and control groups, no difference was observed (P > 0.05) at 24 hours and four days of treatment; while at the eighth (P < 0.05) and fifteenth day (P < 0.01) the treated groups had lower glycemia than the control group, but it was similar among them. Conclusion: The aqueous extract of S. sonchifolius, M. oleifera, and metformin presented similar hypoglycemic effect in experimental rats with induced diabetes. [ABSTRACT FROM AUTHOR]

Objective: To compare the hypoglycemic effect of the aqueous extract of Moringa oleifera (moringa), Smallanthus sonchifolius (yacon) and metformin on Rattus norvegicus, albino variety, with induced diabetes mellitus. Materials and methods: Preclinical, experimental, controlled and randomized study. Diabetes was induced intraperitoneally with a dose of alloxan at 130 mg/kg. A total of 24 male Rattus norvegicus, albino variety, Holfzman strain (6 per group) were used. They were divided as follows: control group (no treatment), metformin group (14 mg/kg), M. oleifera group (200 mg/kg), and S. sonchifolius group (140 mg/kg), treatments were administered via orogastric tube for 15 days. Glycemia levels were determined using an Accu-Chek® Instant electronic glycometer (Roche). Results: Decreased glycemia was observed in the treatment groups: M. oleifera (p = 0.009), S. sonchifolius (p = 0.002) and metformin (p = 0.002), by 313 mg/dL, 281.5 mg/dL and 415 mg/dL, respectively. When comparing glycemia in the treated and control groups, no difference was observed (P > 0.05) at 24 hours and four days of treatment; while at the eighth (P < 0.05) and fifteenth day (P < 0.01) the treated groups had lower glycemia than the control group, but it was similar among them. Conclusion: The aqueous extract of S. sonchifolius, M. oleifera, and metformin presented similar hypoglycemic effect in experimental rats with induced diabetes. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the association between malnutrition, clinical parameters, and health-related quality of life in elderly hospitalized patients with Parkinson's disease (PD). Methods: Cross-sectional study of 92 hospitalized elderly patients with PD (mean age 73.6 ± 6.7 years) without dementia. The Mini Nutritional Assessment (MNA) was used to evaluate nutritional status. Motor impairment and non-motor symptoms burden (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS], Non-Motor Symptoms Questionnaire, and Hoehn & Yahr staging), depression (Becks Depression Inventory-II), and health-related quality of life (PD quality of life Questionnaire-39) were assessed. Results: Every second patient was malnourished or at risk of malnutrition. In the multivariable analysis, male gender, longer disease duration, higher Hoehn & Yahr and depression were associated with total MNA score. Besides non-motor symptoms and motor impairment, malnutrition was an independent predictor of poor health-related quality of life. In the multivariate analysis, malnutrition had a statistically significant effect on emotional well-being, mobility, social support, stigmatization, and cognition. The strongest association was found between malnutrition and emotional well-being. Conclusion: Elderly male persons with longer PD duration and higher disease stages are more likely to be malnourished or at risk for malnutrition. Malnutrition was mainly associated with poor emotional well-being, suggesting that treatment of depression and anxiety beside diet and physical activity can help improving nutrition status in these subjects. The MNA should not be used independent of other measures of cognition and depression in people with advanced PD. [ABSTRACT FROM AUTHOR]

In 2016 Mercedes-Benz SA introduced hybrid vehicles into their East London factory, pioneering high-voltage automotive manufacturing in the country. When the implementation decision was made, the factory was given less than a year to introduce this dangerous new technology at a level that met stringent international safety and quality standards, against a backdrop of a lack of applicable local legislation. This study creates a framework whereby future highvoltage automotive projects can be introduced safely, effectively, and efficiently. The implementation framework for automotive technology (IFAT) was validated against the data of Mercedes- Benz's C350e Plug-in Hybrid Project, and aims to support the local automotive industry in its preparations for e-mobility. [ABSTRACT FROM AUTHOR]

Ischemic stroke due to an acute occlusion of the extracranial internal carotid artery (eICA) is associated with high morbidity and mortality. The best treatment option remains unclear. This study aims to increase the available therapeutic experience documented for surgical recanalization of acute eICA occlusions. We retrospectively reviewed all hospital records of the University Hospital Jena between 2006 and 2018 to identified patients with acute ischemic stroke due to an occlusion of the eICA who underwent emergent surgical recanalization. We analyzed clinical data, surgical reports, imaging data, and outpatient records. The primary outcome parameter was the modified Rankin Scale (mRS) at 3 months. During the survey, 12 patients (mean age: 62.3 ± 10.8 years; range: 35-87) underwent emergent surgical recanalization for an acutely symptomatic eICA occlusion. All patients presented with neurological deficits with a mean National Institutes of Health Stroke Scale score at admission of 15.0 ± 5.1 (range 2-23). Patients were selected for surgery mainly due to the extent of the perfusion mismatch, while stroke severity and age were also considered. The median time from symptom onset to surgery was 309 ± 122 minutes (range 112-650 minutes). Complete recanalization was obtained in all 12 patients. No patient deteriorated postoperatively, no intracranial hemorrhage was observed, and no patient died in the following 3 months. Favorable outcomes (mRS: 0-2) after 3 months were achieved in 7 of 12 patients. The current study adds support to previous findings that the surgical recanalization of acute eICA occlusions is a possible and safe treatment option. However, a critical patient selection based on mismatch size in perfusion imaging is crucially important for successful treatment. [ABSTRACT FROM AUTHOR]

This article compares the long-term outcomes of two different strategies for coronary revascularization: conventional off-pump total arterial revascularization with bilateral internal mammary arteries (BIMA) and hybrid coronary revascularization (HCR). The study retrospectively analyzed patients who received either BIMA (n = 542) or HCR (n = 123) at a single institute. After adjusting for baseline differences, the study found that patients who received BIMA had better 10-year survival and freedom from repeat revascularization compared to those who received HCR. However, the HCR group had a higher incidence of chronic obstructive lung disease, while the BIMA group had a higher incidence of three-vessel coronary artery disease and left main disease. Overall, the study suggests that for otherwise fit patients, conventional off-pump revascularization with BIMA may be the preferred strategy. [Extracted from the article]

This article discusses the use of Minimal Invasive Total Arterial Coronary Artery Bypass Grafting (MICS-CABG) as a surgical approach for treating coronary artery disease in obese patients. The study compared the outcomes of MICS-CABG in obese (BMI >30) and nonobese (BMI<30) patients. The results showed that MICS-CABG is safe and feasible for both obese and nonobese patients, with no significant differences in perioperative and mid-term outcomes. The authors conclude that obesity should not be an exclusion criterion for MICS-CABG in high volume centers. [Extracted from the article]

Background/Aims: Vertebral artery dissection (VAD) is an important cause of ischemic stroke. In this observational study, clinical data, magnetic resonance (MR) and ultrasound (US) imaging findings and ischemic patterns were analyzed. Methods: Forty-seven patients with a diagnosis of VAD underwent clinical examination, US, MR of the brain and neck and MR angiography (MRA) of the cervical arteries. Vascular abnormalities and ischemic brain lesions were noted. Data were evaluated separately and compared for spontaneous and traumatic VAD subgroups. Results: The most common overall clinical symptom was vertigo followed by neck pain. In the traumatic subgroup, vertigo was relatively rare (p = 0.022). Most common MRA findings were vessel irregularity and vessel occlusions. Ischemic lesions occurred significantly more frequently after spontaneous than after traumatic VAD (p = 0.009). Unilateral VAD was significantly more common in non-dominant vertebral arteries (p < 0.001). Mortality after trauma was not only due to VAD complications but also due to other trauma-related injuries. Conclusion: The variability of MR and US imaging findings in patients with VAD is illustrated. The algorithm of management should be based on a multimodality approach involving patient history and clinical neurological examination. Several types of vessel abnormalities and ischemic lesion in diverse locations may point to arterial dissection, and the differential diagnosis of VAD must be kept in mind. [ABSTRACT FROM AUTHOR]

Background: In many functional magnetic resonance imaging (fMRI) studies, experimental design often depends on the eye state (i.e., whether the participants had their eyes open or closed). Closed eyes during an fMRI is the general convention, particularly when patients are in a resting-state, but the eye state is difficult to verify. Although knowledge of the impact of the eye state on brain activity is steadily growing, only a few research groups have implemented standardized procedures to monitor eye movements and eye state. These procedures involve advanced methods that are costly (e.g., fMRI-compatible cameras) and often time-consuming (e.g., EEG/EOG).Results: We present a simple method that distinguishes open from closed eyes utilizing functional MR images alone. The utility of this method was demonstrated on fMRI data from 14 healthy subjects who had to open and close their eyes according to a predetermined protocol (3.0 T MRI scanner, EPI sequence with 3 × 3 × 3 mm voxels, TR 2.52 s).Conclusion: The method presented herein is capable of extracting the movement direction of the eyes. All described methods are applicable for pre- and post-normalized MR images and are freely available through a MATLAB toolbox. [ABSTRACT FROM AUTHOR]

Summary Epileptic seizures rank among the most frequent neurologic symptoms during the neonatal period. Accumulating data from experimental animal studies and clinical trials in humans suggest that neonatal seizures could adversely affect normal brain development and result in long-term neurologic sequelae. Unfortunately, currently used anticonvulsive drugs are often ineffective in the neonatal period. One particularity of the immature neuronal network during neonatal development is that the neurotransmitter γ-aminobutyric acid (GABA) is mainly depolarizing, rather than hyperpolarizing as commonly observed in adults. This might, in part, explain not only the higher seizure propensity of the immature neuronal network, but also the limited anticonvulsive efficacy of GABA-enhancing drugs during early postnatal life. Accordingly, pharmacologic attenuation of GABAergic depolarization has been proposed as a strategy for neonatal seizure control. However, the underlying conjecture of a depolarizing mode of GABA action has been seriously challenged recently. In the present review, we will summarize the state of knowledge regarding GABAergic depolarization in early life and discuss how these data might impact a currently tested anticonvulsive strategy. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSC) are multipotent cells capable of differentiating into adipocytic, chondrocytic and osteocytic lineages on suitable stimulation. We have hypothesized that mechanical loading may influence MSC differentiation and alter their phenotype accordingly. Mouse bone marrow-derived MSC were established in vitro by differential adherence to plastic culture plates and grown in low glucose medium with 10% foetal calf serum and growth factors. Cells grew out and were subcultured up to 20 times. Differentiation protocols were followed for several cell lineages. Clones with trilineage potential were seeded in type I collagen gels and incubated in a tensioning force bioreactor and real-time cell-derived forces were recorded. Gels were fixed and sectioned for light and electron microscopy. Cell monolayers of parent and cloned mouse bone marrow-derived MSC differentiated into adipocytes, osteocytes and chondrocytes, but not into cardiomyocytes, myotubes or neuronal cells. When cast into type I collagen gels and placed in tensioning bioreactors, MSC differentiated into fibroblast-like cells typical of tissue stroma, and upregulated α-smooth muscle actin, but rarely upregulated desmin. Electron microscopy showed collagen and elastin fibre synthesis into the matrix. These experiments confirmed that MSC cell fate choice depends on minute, cell-derived forces. Applied force could assist in commercial manufacture of cultured bio-engineered prostheses for regenerative medicine as it mimics tissue stresses and constitutes a good model for development of tissue substitutes. [ABSTRACT FROM AUTHOR]

A large body of evidence suggests that the neurotransmitter GABA undergoes a developmental switch from being predominantly depolarizing- excitatory to predominantly hyperpolarizing-inhibitory. Recently published data, however, point to the possibility that the presumed depolarizing mode of GABA action during early development might represent an artifact due to an insufficient energy supply of the in vitro preparations used. Specifically, addition of the ketone body DL-β-hydroxybutyrate (βHB) to the extracellular medium was shown to prevent GABA from exerting excitatory effects. Applying a complementary set of minimally invasive optical and electrophysiological techniques in brain slices from neonatal mice, we investigated the effects of βHB on GABA actions in immature cells of the upper cortical plate. Fluorescence imaging revealed that GABA-mediated somatic [Ca2+] transients, that required activation of GABAA receptors and voltage-gated Ca2+ channels, remained unaffected by βHB. Cell-attached current-clamp recordings showed that, in the presence of βHB, GABA still induced a membrane potential depolarization. To estimate membrane potential changes quantitatively, we used cell-attached recordings of voltage-gated potassium currents and demonstrated that the GABA-mediated depolarization was independent of supplementation of the extracellular solution with βHB. We conclude that, in vitro, GABA depolarizes immature cells of the upper cortical plate in the presence of the ketone body βHB. Our data thereby support the general concept of an excitatory-to-inhibitory switch of GABA action during early development. [ABSTRACT FROM AUTHOR]

Background: We used a PCR-based approach to study the prevalence of genetic sequences related to a gammaretrovirus, xenotropic murine leukemia virus-related virus, XMRV, in human prostate cancer. This virus has been identified in the US in prostate cancer patients and in those with chronic fatigue syndrome. However, with the exception of two patients in Germany, XMRV has not been identified in prostate cancer tissue in Europe. Most putative associations of new or old human retroviruses with diseases have turned out to be due to contamination. We have looked for XMRV sequences in DNA extracted from formalin-fixed paraffin- embedded prostate tissues. To control for contamination, PCR assays to detect either mouse mitochondrial DNA (mtDNA) or intracisternal A particle (IAP) long terminal repeat DNA were run on all samples, owing to their very high copy number in mouse cells. Results: In general agreement with the US prevalence, XMRV-like sequences were found in 4.8% of prostate cancers. However, these were also positive, as were 21.5% of XMRV-negative cases, for IAP sequences, and many, but not all were positive for mtDNA sequences. Conclusions: These results show that contamination with mouse DNA is widespread and detectable by the highly sensitive IAP assay, but not always with less sensitive assays, such as murine mtDNA PCR. This study highlights the ubiquitous presence of mouse DNA in laboratory specimens and offers a means of rigorous validation for future studies of murine retroviruses in human disease. [ABSTRACT FROM AUTHOR]

Validation of body-mass relationships requires a careful statistical analysis of data of normal weight individuals. BMI (ratio between body mass and square of body height) and BSI values (ratio between mass and cube of body height) have been calculated for 99 persons with ages between 1 day and 76 years. These BMI or BSI values have been used for least squares fits yielding mean BMI or BSI values, their variances (providing precision), and average deviations of individual BMI/BSI values from the BMI/BSI means. The latter allows limits to over- and underweight. For adults we found mean values of BSI of 12.36 and confirmed 21.7 for the mean BMI; but the BSI was 1.4 times more precise than the BMI. For children shorter than 1.3m and younger than 8 years we found the BMI average of 15.9 and over-/underweight limits of 17.4/14.4 being significantly smaller than and incompatible with the recommended BMI values. [ABSTRACT FROM AUTHOR]

Objective: Various studies have shown that bone marrow stem cells can rescue mice from acute renal tubular damage under a conditioning advantage (irradiation or cisplatin treatment) favouring donor cell engraftment and regeneration; however, it is not known whether bone marrow cells (BMCs) can contribute to repair of acute tubular damage in the absence of a selection pressure for the donor cells. The aim of this study was to examine this possibility. Materials and methods: Ten-week-old female mice were assigned into control non-irradiated animals having only vehicle treatment, HgCl2-treated non-irradiated mice, HgCl2-treated non-irradiated mice infused with male BMCs 1 day after HgCl2, and vehicle-treated mice with male BMCs. Tritiated thymidine was given 1 h before animal killing. Results: Donor BMCs could not alleviate non-irradiated mice from acute tubular damage caused by HgCl2, deduced by no reduction in serum urea nitrogen combined with negligible cell engraftment. However, donor BMCs could home to the bone marrow and spleen and display proliferative activity. This is the first report to show that despite no preparative myeloablation of recipients, engrafted donor BMCs can synthesize DNA in the bone marrow and spleen. Conclusions: Exogenous BMCs do not rescue non-irradiated mice from acute renal tubular damage caused by HgCl2, despite establishment of chimerism and cell proliferation in bone marrow and spleen. [ABSTRACT FROM AUTHOR]

Objective: Our previous studies have demonstrated that endogenous bone marrow cells (BMCs) contribute to renal tubular regeneration after acute tubular injury. The aim of this study was to examine which fraction of BMCs, haematopoietic lineage marrow cells (HLMCs) or mesenchymal stem cells (MSCs), are effective. Materials and methods: Six-week-old female mice were lethally irradiated and were transplanted with female enhanced green fluorescent protein-positive (GFP+), plastic non-adherent marrow cells (as a source of HLMCs) plus cloned cultured male GFP− MSCs. Four weeks later, they were assigned into two groups: control mice with vehicle treatment and mice treated with HgCl2. Tritiated thymidine was given 1 h before animal killing which occurred at intervals over 2 weeks. Kidney sections were stained for a tubular epithelial marker, cell origin indicated by GFP immunohistochemistry or Y chromosome in situ hybridization; periodic acid-Schiff staining was performed, and samples were subjected to autoradiography. One thousand consecutive renal tubular epithelial cells per mouse, in S phase, were scored as either female (indigenous) GFP+ (HLMC-derived) or male (MSC-derived). Results: Haematopoietic lineage marrow cells and MSCs stably engrafted into bone marrow and spleen, but only HLMC-derived cells, not MSCs, were found in the renal tubules and were able to undergo DNA synthesis after acute renal injury. A few MSCs were detected in the renal interstitium, but their importance needs to be further explored. Conclusion: Haematopoietic lineage marrow cells, but not cloned cultured MSCs, can play a role not only in normal wear-and-tear turnover of renal tubular cells, but also in repair after tubular injury. [ABSTRACT FROM AUTHOR]

Up to halfway or two thirds of the way through the last century, the treatments available for the treatment of shoulder injuries were mainly conservative, and in many cases the results observed after external immobilization in different splints, fixation devices or plaster casts for 3 or more weeks were not satisfactory. With the development and introduction of really adequate operative methods it became possible to perform reconstruction and functional rehabilitation tailored to the different injuries, with much better anatomical and functional results. Due consideration must also be given to the patients' wishes and any economic restrictions imposed by hospital managements and healthcare insurances. Conservative measures are being pushed more and more into the background, and a good many of them are already completely forgotten. Remembering them also evokes appropriate appreciation of the successes that have become possible through operative procedures. [ABSTRACT FROM AUTHOR]

Abstract: Several types of CNS injury and various diseases are associated with the development of a glial scar. Astrocytes are major components of the glial scar. They are interconnected by gap junctions, with connexin43 (Cx43) being the most prominent channel protein. We applied a model of focal cerebral ischemia to study the spatio-temporal expression of glial fibrillary acidic protein, as well as of Cx43 mRNA and protein in gliotic tissue up to 60 days after injury. Reactive astrocytes enveloping the lesion up-regulated their Cx43 mRNA and protein. A band of reactive astrocytes filling in the lesion exhibited elevated Cx43 and showed a high degree of proliferation. Because of these findings, we hypothesize a role for Cx43 in glial scar formation, specifically in the proliferation of astrocytes. [Copyright &y& Elsevier]

Background: Infection of pancreatic necrosis is the most dangerous complication of acute necrotizing pancreatitis. Infection is undoubtedly caused by the endogenous flora of the host. This is why prophylaxis with a broad-spectrum antibiotic is considered an effective procedure. However, two aspects should be taken into consideration when choosing the antibiotic; it should have the spectrum of action consistent with the pathogens and it should penetrate effectively to the necrotic tissue of the pancreas. The aim of the study was to estimate the efficacy of piperacillin/tazobactam penetration into pancreatic necrosis in patients who received intravenous infusion of piperacillin/tazobactam at a dose of 4.5 g every 8 h for 14–21 days, as the prophylaxis in the treatment of acute necrotizing pancreatitis. Patients and methods: Necrotic tissue of the pancreas and the inflammatory ascites surrounding the pancreas were derived from 15 patients (male, 10; female, 5; mean age 46 years), who underwent laparatomy due to pancreatic necrosis after treatment for 14–21 days. Tissue/fluid samples were investigated for the concentration of the antibiotic by fluoroscopic/spectroscopic methods of registration in an HPLC system. Results: The mean concentration of piperacillin/tazobactam was established as 120 mg/kg (SD±34) in the necrotic pancreatic tissue and as 183 mg/kg (SD±37) in the inflammatory pancreatic ascites. Conclusions: In patients with acute necrotizing pancreatitis, the study indicates effective penetration of piperacillin/tazobactam to the necrotic pancreatic tissue and to the inflammatory ascites surrounding the pancreas. [ABSTRACT FROM AUTHOR]

B Background: b The short-term Results of reconstruction of the hepatic duct injury are excellent; the long-term outcome is however doubtful. B Conclusion: b The result of reconstruction depends on causes of the referral that in turn arise from the subsequent intervention taken in the hospitals. [Extracted from the article]

Trefoil factor family (TFF) peptides have many in vivo and in vitro effects on restitution, wound healing, apoptosis, cell motility, adhesion and vectorial ion pumping, amongst others. 125I-TFF peptides bind to cell membranes with classical saturable ability. It would be surprising if there were not TFF-protein interactions that would explain these actions, but to date no convincing TFF-binding partner has been shown which unambiguously takes part in any of these functions. Nevertheless, several TFF-binding proteins exist, including the small intestinal CRP-ductin (muclin), which binds TFF2, and the recently described gastric foveolar proteins TFIZ1 (TFF1-binding) and blottin (TFF2-binding), any of which may yet interact in novel ways to elicit TFF-mediated events. This review describes the expression and, where known, the functions of such proteins. [ABSTRACT FROM AUTHOR]

The regeneration of sensory nerve fibres is regulated by trophic factors released from their target tissue, particularly the basal epidermis, and matrix molecules. Means to modulate this response may be useful for the treatment of neuromas and painful hypertrophic scars and of sensory deficits in skin grafts and flaps. We have developed an in vitro model of sensory neuron regeneration on human skin in order to study the mechanisms of sensory dysfunction in pathological conditions. Adult rat sensory neurons were co-cultured with unfixed cryosections of normal or injured (crushed) human skin for 72 h. Neurons were immunostained for growth-associated protein-43 and the neurite lengths of neuronal cell bodies situated in various skin regions were measured. Two-way analysis of variance was performed. Neurites of sensory cell bodies on epidermis of normal skin were the shortest, with a mean ± SEM of 75±10 μm, whereas those of cells on the dermo-epidermal junction were the longest, with a mean ± SEM of 231±18 μm. Neurons on the dermo-epidermal junction of injured skin had significantly longer neurites than those on the same region of normal skin (mean ± SEM = 289±21 μm). Regeneration of sensory neurons may be influenced by extracellular matrix molecules, matrix-binding growth factors and trophic factors. Altered substrate or trophic factors in injured skin may explain the increase of neurite lengths. This in vitro model may be useful for studying the molecular mechanisms of sensory recovery and the development of neuropathic pain following peripheral nerve injury. [ABSTRACT FROM AUTHOR]

A Christian approach to the issues that constitute bioethics is inevitable for us who cherish the truth of historic, creedal, trinitarian Christianity. Scripture teaches and the Greek and Latin Church Fathers as well as the Reformers aver that man, created in the image of God, has an inherent, if vestigial, sense of right and wrong and a conscience however marred by the fall and by rebellion. We must believe that we share this most basic ecumenism with all humanity, not because of rational observation and analysis of nature, but because Scripture reveals it. We who are convinced of the truth of historic, creedal, trinitarian Christianity have a high view of Scripture and hold it to be infallible and utterly trustworthy irrespective of the importance we assign to our specific post-biblical traditional distinctives. This is a narrower but much more vital ecumenism than the first. Faithful adherence to Scripture inevitably manifests itself in remarkably similar priorities and values, often, lamentably, not because of, but in spite of, ourselves. [ABSTRACT FROM AUTHOR]

The present study is a crossvalidation in the Fair Oaks Raleigh Hills Hospital of a 1970 outcome study by Wiens et al. from the Portland Raleigh Hills Hospital. The 1975 Fair Oaks crossvalidation sample included all 275 patients treated during 1975. These results were further recrossvalidated using all 290 patients treated in the Fair Oaks hospital during 1976. Results were 12-mo abstinence levels of 63% for the 1970 Portland sample and 39% and 50%, respectively, for the two Fair Oaks cross-validation samples. If the more stringent total abstinence without a slip of a single drink was the outcome measure used, these 1975 and 1976 12-mo abstinence levels became 33% and 43%, respectively. Additional analyses revealed the important role in these outcome rates of such demographic variables as Medicare recipient status, marital status, employment status, and a combined status of married and employed. [ABSTRACT FROM AUTHOR]

The study objective was to study whether the microsatellite instability of colorectal carcinoma has impact on the angiogenesis activity in the liver metastases. The endothelial progenitor cells fraction (CD309+) was enumerated within the subpopulation of CD34+CD45+ cell and CD34+CD45- cells by flow cytometer in the blood samples. B Conclusion: b The MSI colorectal cancers are characterized by the overexpression of circulating EPCs and VEGF which may facilitate their growth and metastases. [Extracted from the article]

The study objective was to study whether the microsatellite instability of colorectal carcinoma has impact on the angiogenesis activity in the liver metastases. The endothelial progenitor cells fraction (CD309+) was enumerated within the subpopulation of CD34+CD45+ cell and CD34+CD45- cells by flow cytometer in the blood samples. B Conclusion: b The MSI colorectal cancers are characterized by the overexpression of circulating EPCs and VEGF which may facilitate their growth and metastases. [Extracted from the article]

B Background: b The short-term results of reconstruction of the hepatic duct injury are excellent; the long-term outcome is however doubtful. B Conclusion: b The result of reconstruction depends on causes of the referral that in turn arise from the subsequent intervention taken in the hospitals. [Extracted from the article]

[Display omitted] • Treatment with PLX5622 leads to a dose-dependent depletion of microglia. • Treatment with PLX5622 differentially affected cytokines in young and aged mice. • Low doses lead to reduction in inflammation circumventing the astrocyte activation. • Depletion of microglia led to decreased expression of the senescence marker p16. • Brain inflammation can be reduced by reducing the microglial cell population. Chronic macrophage activation was implicated as one of the main culprits for chronical, low-grade inflammation which significantly contributes to development of age-related diseases. Microglia as the brain macrophages have been recently implicated as key players in neuroinflammation and neurodegeneration in the aged brain. Microglial cell functions are indispensable in early development, however, activation or senescence of microglia in aging cells may be detrimental. Depletion of microglia using genetical or pharmacological approaches leads to opposite results regarding effects on brain cognition. In this study we pharmacologically depleted microglia using orally delivered low and high doses of the CSF1R inhibitor PLX5622 and assessed the expression levels of known inflammation markers (TNF-α, IL1-β, IL-6, IL-10), glia markers (Iba-1 and Gfap) and specific senescence marker p16Ink4a in the aged murine brain. Our results indicate that treatment with low and high doses of PLX5622 leads to a dose-dependent depletion of microglial cells with similar levels in young and aged mice. We also show that treatment with low and high PLX5622 differentially affected cytokine levels in young and old brains. By using low doses we could achieve reduction in inflammation circumventing the astrocyte activation. Removal of microglia cells led to decreased expression of the senescence marker p16Ink4a in the aged brain, indicating a relevant contribution of these cells to the expression of this marker and their senescent status in the healthy aging brain. Our results indicate that increased and detrimental brain inflammation in aged murine brain can be impaired by selectively reducing the microglial cell population. [ABSTRACT FROM AUTHOR]

• We determined microglia expression of critical metabolic rate limiting enzymes. • We found different metabolic changes occurring in senescent vs. aged microglia cells. • Senescent microglia display glycolysis activation and hypermetabolic state. • Aged microglia are rather in a state of hypometabolism. • Metabolic changes in aged microglia may present a novel therapeutical target. Microglia, the resident immune cells of the central nervous system, are critically involved in maintaining brain homeostasis. With age, microglia display morphological and functional alterations that have been associated with cognitive decline and neurodegeneration. Although microglia seem to participate in an increasing number of biological processes which require a high energy demand, little is known about their metabolic regulation under physiological and pathophysiological conditions and during aging/senescence. Here, we determined mRNA expression levels of critical rate limiting enzymes in several key metabolic pathways including glycolysis, pentose phosphate pathway, fatty acid oxidation and synthesis in association with oxidative phosphorylation in microglia, both under aging and senescent conditions. We found strong evidence for different metabolic changes occuring in senescent vs. aged microglia cells. While senescent microglia display a hypermetabolic state as indicated by increased expression of key enzymes involved in glycolysis and pentose phosphate pathway, aging microglia are rather in a state of hypometabolism. Our findings indicate that studies involving aging and senescent microglia require a clear differentiation between these microglial states due to profound metabolic differences observed here. Understanding metabolic changes in senescent and aged microglia may lead to novel strategies to decrease over-activation of these cells due to aging, which is associated to the process of inflamm-aging and neurodegeneration. [ABSTRACT FROM AUTHOR]

The integral membrane zinc metalloprotease ZMPSTE24 plays a key role in the proteolytic processing of farnesylated prelamin A, the precursor of the nuclear scaffold protein lamin A. Failure of this processing step results in the accumulation of permanently farnesylated forms of prelamin A which cause the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS), as well as related progeroid disorders, and may also play a role in physiological aging. ZMPSTE24 is an intriguing and unusual protease because its active site is located inside of a closed intramembrane chamber formed by seven transmembrane spans with side portals in the chamber permitting substrate entry. The specific features of prelamin A that make it the sole known substrate for ZMPSTE24 in mammalian cells are not well-defined. At the outset of this work it was known that farnesylation is essential for prelamin A cleavage in vivo and that the C-terminal region of prelamin A (41 amino acids) is sufficient for recognition and processing. Here we investigated additional features of prelamin A that are required for cleavage by ZMPSTE24 using a well-established humanized yeast system. We analyzed the 14-residue C-terminal region of prelamin A that lies between the ZMPSTE24 cleavage site and the farnesylated cysteine, as well 23-residue region N-terminal to the cleavage site, by generating a series of alanine substitutions, alanine additions, and deletions in prelamin A. Surprisingly, we found that there is considerable flexibility in specific requirements for the length and composition of these regions. We discuss how this flexibility can be reconciled with ZMPSTE24's selectivity for prelamin A. [ABSTRACT FROM AUTHOR]

Background. Medication is often changed after hospital discharge in people with Parkinson's disease (PD). Objective. This observational study aimed to describe changes in PD medication after discharge and explore their association with self-reported adherence and clinical parameters. Methods. During hospitalisation sociodemographic characteristics, the Movement Disorder Society-sponsored revision of the Unified PD Rating Scale for motor function (MDS-UPDRS III), Hoehn and Yahr (H&Y) stage, levodopa equivalent daily dose (LEDD), Beck Depression Inventory II (BDI-II) score, Montreal Cognitive Assessment (MoCA) score, nonmotor symptoms questionnaire (NMSQ), and Stendal Adherence to Medication Score (SAMS) were collected in 125 people with PD. A semistructured interview was conducted 1 month after discharge to determine the extent and reasons for medication changes. Results. Thirty-eight patients (30.4%) changed their PD medication after discharge. Most changes (20.8%) were performed by physicians while 9.6% of patients changed their medication by themselves due to side effects, missing effect of the medication, missing knowledge about the indication, running out of medication, or nonspecific reason. This led to decreased doses while changes by physicians resulted in both increase and decrease of doses as well as new drug prescription. Patients without changes, patients with changes performed by them, and patients with changes performed by physicians did not differ in age, disease duration, MDS-UPDRS III, LEDD, NMSQ, MoCA, BDI-II, gender, marital status, or education. However, patients who themselves made the changes were more likely to be nonadherent according to baseline SAMS. Patients who made changes after discharge had higher SAMS modification and forgetting subscores than patients without changes or with changes made by physicians. Conclusion. Both intended and unintended nonadherence occur in patients who change medication after discharge. The use of an adherence questionnaire during inpatient treatment may help detect patients with higher risk of changing medication after discharge. [ABSTRACT FROM AUTHOR]

The task of learning predefined sequences of interrelated motor actions is of everyday importance and has also strong clinical importance for regaining motor function after brain lesions. A solid understanding of sequence learning in stroke patients can help clinicians to optimize and individualize rehabilitation strategies. Moreover, to investigate the impact of a focal lesion on the ability to successfully perform motor sequence learning can enhance our comprehension of the underlying physiological principles of motor sequence learning. In this article, we will first provide an overview of current concepts related to motor sequence learning in healthy subjects with focus on the involved brain areas and their assumed functions according to the temporal stage model. Subsequently, we will consider the question of what we can learn from studies investigating motor sequence learning in stroke patients. We will first focus on the implications of lesion location. Then, we will analyze whether distinct lesion locations affect specific learning stages. Finally, we will discuss the implications for clinical rehabilitation and suggest directions for further research. [ABSTRACT FROM AUTHOR]

Aims To examine the diversity of Staphylococcus aureus isolated from nasal swabs of ruminants in Rwanda. Methods and results A total of 454 nasal swabs from 203 cows, 170 goats, and 81 sheep were examined for the presence of S. aureus , and 30 S. aureus isolates were detected and characterized pheno- and genotypically. Resistance to penicillin and/or tetracycline was observed. The isolates were assigned to eight different spa types (t21057 (novel), t10103, t18853, t20842, t318, t355, t458, and t9432) belonging to six clonal complexes (CCs) (CC152, CC30, CC3591, CC3666, CC522, and CC97). Panton–Valentine leukocidin (PVL) genes (lukF-PV/lukS-PV), the bovine leukocidin genes (lukM/lukF-P83), and the human and bovine variants of the toxic shock syndrome toxin gene tst-1 variants were detected. Conclusion These findings demonstrate that the nares of ruminants in Rwanda are colonized with mastitis-associated S. aureus , including lineages that are also carried by humans, underscoring the zoonotic risk, especially for livestock keepers. These results highlight the crucial importance of hygiene measures when handling livestock. [ABSTRACT FROM AUTHOR]

In this randomized controlled intervention trial, we investigated whether intense visual stimulation through television watching can enhance visual information processing and motor learning performance. 74 healthy young adults were trained in a motor skill with visual information processing demands while being accommodated in a controlled environment for five days. The experimental manipulation (n = 37) consisted of prolonged television watching (i.e., 8 h/day, + 62.5% on average) to induce intense exposure to visual stimulation. The control group (n = 37) did not consume visual media. The groups were compared by motor learning performance throughout the study as well as pre/post visual attention parameters and resting-state network connectivity in functional MRI. We found that the intervention group performed significantly better in the motor learning task (+ 8.21% (95%-CI[12.04, 4.31], t(70) = 4.23, p < 0.001) while showing an increased capacity of visual short-term memory (+ 0.254, t(58) = − 3.19, p = 0.002) and increased connectivity between visual and motor-learning associated resting-state networks. Our findings suggest that the human brain might enter a state of accentuated visuomotor integration to support the implementation of motor learning with visual information processing demands if challenged by ample input of visual stimulation. Further investigation is needed to evaluate the persistence of this effect regarding participants exposed to accustomed amounts of visual media consumption. Clinical Trials Registration: This trial was registered in the German Clinical Trials Register/Deutsches Register klinischer Studien (DRKS): DRKS00019955. [ABSTRACT FROM AUTHOR]