Mccoygibbons6979

Rotator cuff tears are a common pathology in the shoulder and generally have two underlying etiologies traumatic and degenerative. Little is known about the molecular underpinning of these etiologies. Here we queried transcript level differences in tear etiology stratified by sex in 31 patients with rotator cuff tears. Tendon tissues were isolated from females (N = 16) and males (N = 15) with traumatic (N = 16) or degenerative (N = 15) tears during arthroscopy. Differentially expressed transcripts were identified by RNA-seq and biological processes were probed computationally. Expression of some transcripts was validated by real-time quantitative polymerase chain reaction (qPCR). We identified 339 and 336 transcripts differentially expressed by tear etiology in females and males, respectively, at a fold-change greater than |2|. In females, GSTM1, MT1G, S1008A, ACSM3, DSC, FAM110C, and VNN2 were elevated in traumatic tears representing metabolic/catabolic processes, and immune response whereas CHAD, CLEC3A, IBSP, TNMD, APLNR, and CPA3 were elevated in degenerative tears representing tissue morphogenesis and developmental processes, angiogenesis, and extracellular matrix organization. In males, ELOA3B, CXCL8, ADM, TNS4, and SPOCK1 were elevated in traumatic tears representing localization of endoplasmic reticulum, chromosome organization, leukocyte/neutrophil degranulation, and protein transport whereas MYL2, TNNC1, MB, CPA3, APLNR, and CA3 were highly upregulated in degenerative tears representing muscle cell differentiation and development and angiogenesis. Numerous novel lncRNAs were identified to be differentially expressed by tear etiology in both sexes. Real-time qPCR confirmed RNA-seq data. This study improves our understanding of tendon biology based on underlying etiology (trauma or degeneration) in a sex-specific manner. These findings may help drive clinical decision-making in females and males with traumatic and degenerative shoulder injuries.Stearyl alcohol is found in various cosmetics and topical medications and is regarded as safe. Allergic contact dermatitis is reported due to this chemical on rare occasions. We report seven cases, comprising three men and four women aged between 36 and 62 between the years 2013 to 2019, of allergic contact dermatitis due to the use of topical medication, where the patient showed a positive result to a patch test using stearyl alcohol. There were 10 topical medications that we considered to be the cause of this three were from Oronine® H ointment, two from Eurax® cream, one from Eurax H cream, and four from topical antifungal medications. All these medications contained stearyl alcohol. Seven cases of patch tests with stearyl alcohol all showed positive results. Moreover, having done a patch test with cetyl alcohol, two out of three tests showed positive. When researching allergic contact dermatitis due to topical medications, it is important to test for allergy to stearyl alcohol as well as their main ingredients, because it is contained in numerous products and has the ability to cause allergic contact dermatitis.Skin sense organs, cutaneous sensilla, are a well-known feature of the integument of squamate reptiles and particularly geckos. They vary widely in morphology among species and are thought to be mechanosensitive, associated with prey capture and handling, tail autotomy and placement of the adhesive toepads in pad-bearing species. Some authors suggest that they may also sense abiotic environmental features, such as temperature or humidity. Here, we describe the morphology and distribution of cutaneous sensilla among body regions of nine Australian gecko species, in four genera. We hypothesised that if sensilla morphology was distinct, or sensilla density high, around the mouth, on the tail and on extremities, sensilla were likely used for these direct tactile functions. We found that sensilla morphology was uniform among body regions within species, but varied among species, while sensilla densities varied among species and body regions. In all species studied, sensilla density was highest on the labials and the dorsal tail scales and low on the feet, head and body, providing strong support for the hypothesis that sensilla serve tactile mechanoreceptive functions for prey capture and handling and for predator avoidance, but not for toepad placement. We suggest sensilla density may be explained by mechanoreception, whereas structure may be influenced by other factors.Advanced prostate cancer often develops into bone metastasis, which is characterized by aberrant bone formation with chronic pain and lower chances of survival. No treatment exists as yet for osteoblastic bone metastasis in prostate cancer. The indolamine melatonin (N-acetyl-5-methoxytryptamine) is a major regulator of the circadian rhythm. Melatonin has shown antiproliferative and antimetastatic activities but has not yet been shown to be active in osteoblastic bone lesions of prostate cancer. Our study investigations reveal that melatonin concentration-dependently decreases the migratory and invasive abilities of two osteoblastic prostate cancer cell lines by inhibiting FAK, c-Src, and NF-κB transcriptional activity via the melatonin MT1 receptor, which effectively inhibits integrin α2 β1 expression. Melatonin therapy appears to offer therapeutic possibilities for reducing osteoblastic bone lesions in prostate cancer.Direct oral anticoagulants (DOACs) are now an option in the prevention and treatment of venous thromboembolic events (VTE) in patients with active cancer. Pharmacokinetics of DOACs are largely influenced by efflux transporters derived from ABC transporters, notably by P-glycoprotein (P-gp). The aim of this study was to assess the potential P-gp-mediated drug-drug interactions between 11 tyrosine kinase inhibitors (TKIs) with apixaban and rivaroxaban. Bidirectional permeabilities of apixaban and rivaroxaban were investigated across MDCK-MDR1 models, to determine half maximal inhibitory concentration (IC50 ). Several categories of interaction risks based on IC50 values can be distinguished depending on the TKI and DOAC used. IC50 values of less than 10 μM were observed with the combination of erlotinib, nilotinib with both DOACs, and with dabrafenib and apixaban. IC50 values between 10 and 100 μM were seen for axitinib, crizotinib, dasatinib, imatinib, and lapatinib with apixaban, and for axitinib, crizotinib, dabrafenib, idelalisib, imatinib, and vemurafenib with rivaroxaban. A risk of drug-drug interaction was found in vitro between TKIs and DOACs. In vivo pharmacokinetic studies are needed to ensure the safety of prescribing DOACs in cancer patients on TKI therapy, in order to avoid major, potentially preventable bleeding events.

Information on the incidence of adrenal trauma and its association with other injuries is limited. Our objective was to study the incidence of adrenal haemorrhage, its association with other injuries, clinical parameters, and long-term outcomes.

All patients treated for severe abdominal trauma (Level 1) at Karolinska University Hospital, Solna, between January 1, 2013 and December 31, 2018 were included. Patients with a radiological picture of adrenal haematoma were selected. The injury severity score (ISS) was analysed in the entire cohort. Data were collected from the electronic medical files.

In total, 1.7% (n = 29/1743) was affected by adrenal trauma. Right adrenal trauma (n = 20/29;69%) was more common than left (n = 6/29;21%, p < 0.01), and 10% were bilateral (n = 3/29). There was no difference in volume in right versus left adrenal trauma [(median 13 (interquartile range (IQR) (7-15) versus 8 (5-13)] ml, p = 0.30). ISS was 23.4 (17-43) in adrenal haematoma patients, higher compared with other trauma patients 16 (8-27) (n = 1714)(p < 0.001). Rib fractures, pneumothorax, and liver lacerations were the three most common findings in association with adrenal trauma. The underlying cause in 48% of the cases was fallingfrom height (≥3 m). Biochemical data demonstrated normal sodium and potassium levels while the lowest haemoglobin level was 72 g/l. At follow-up, 4 (2-6) years after the trauma, except for three patients who died as in-patients, all other persons were still living. None seemed to have adrenal insufficiency.

Adrenal trauma is rare and does not seem to be associated with clinical features of adrenal insufficiency, even if the bleeding is bilateral.

Adrenal trauma is rare and does not seem to be associated with clinical features of adrenal insufficiency, even if the bleeding is bilateral.

We aim to seek expert opinion and gain consensus on the risks associated with a range of prescribing scenarios, preventable using e-prescribing systems, to inform the development of a simulation tool to evaluate the risk and safety of e-prescribing systems (ePRaSE).

We conducted a two-round e-Delphi survey where expert participants were asked to score pre-designed prescribing scenarios using a five-point Likert scale to ascertain the likelihood of occurrence of the prescribing event, likelihood of occurrence of harm and the severity of the harm.

Twenty-four experts consented to participate with 15 pand 13 participants completing rounds 1 and 2, respectively. Experts agreed on the level of risk associated with 136 out of 178 clinical scenarios with 131 scenarios categorised as high or extreme risk.

We identified 131 extreme or high-risk prescribing scenarios that may be prevented using e-prescribing clinical decision support. The prescribing scenarios represent a variety of categories, with drug-diseas has achieved expert consensus on the risk associated with a range of clinical scenarios with most of the scenarios categorised as extreme or high risk. These prescribing scenarios represent the breadth of preventable prescribing error categories involving both basic and advanced clinical decision support. We will use the findings of this study to inform the development of the e-prescribing risk and safety evaluation tool.Persisters are a subpopulation that exhibit growth suppression, antibiotic tolerance, and regrowth after antibiotic removal, without any genetic mutations, which causes the recalcitrance and recurrence of infectious diseases. Persisters are majorly induced through the repression of energy metabolism, but some exceptions have been reported. We have previously shown that ldhA, which encodes lactate dehydrogenase, induces Escherichia coli persisters, resulting in a state of high-energy metabolism. However, the detailed mechanism of persister formation upon ldhA expression remains elusive. learn more In the present study, we focused on the SOS response pathway via the DNA repair pathway that consumes adenosine triphosphate and revealed that the SOS response pathway is activated upon ldhA expression even before antimicrobial treatment. Metabolome analysis of ldhA-overexpressing cells revealed that nucleotide metabolic pathways, such as de novo purine biosynthesis, were activated to prepare a nucleotide pool, as substrate for repairing ofloxacin-induced DNA damage. We provide a novel persister model that contributes to survival as a species by "accidentally" activating the SOS response even before receiving antimicrobial stress.