Antibiotics changed medical practice by significantly decreasing the morbidity and mortality associated with bacterial infection. However, infectious diseases remain the leading cause of death in the ...world. There is global concern about the rise in antimicrobial resistance (AMR), which affects both developed and developing countries. AMR is a public health challenge with extensive health, economic, and societal implications. This paper sets AMR in context, starting with the history of antibiotics, including the discovery of penicillin and the golden era of antibiotics, before exploring the problems and challenges we now face due to AMR. Among the factors discussed is the low level of development of new antimicrobials and the irrational prescribing of antibiotics in developed and developing countries. A fundamental problem is the knowledge, attitude, and practice (KAP) regarding antibiotics among medical practitioners, and we explore this aspect in some depth, including a discussion on the KAP among medical students. We conclude with suggestions on how to address this public health threat, including recommendations on training medical students about antibiotics, and strategies to overcome the problems of irrational antibiotic prescribing and AMR.
100 Questions in Livestock Helminthology Research Morgan, Eric R.; Aziz, Nor-Azlina A.; Blanchard, Alexandra ...
Trends in parasitology,
January 2019, 2019-01-00, 20190101, 2019-01, 2019, Letnik:
35, Številka:
1
Journal Article
Recenzirano
Odprti dostop
An elicitation exercise was conducted to collect and identify pressing questions concerning the study of helminths in livestock, to help guide research priorities. Questions were invited from the ...research community in an inclusive way. Of 385 questions submitted, 100 were chosen by online vote, with priority given to open questions in important areas that are specific enough to permit investigation within a focused project or programme of research. The final list of questions was divided into ten themes. We present the questions and set them briefly in the context of the current state of knowledge. Although subjective, the results provide a snapshot of current concerns and perceived priorities in the field of livestock helminthology, and we hope that they will stimulate ongoing or new research efforts.
Important questions on helminths of livestock were elicited across the research community and prioritised by online vote.
The approach contrasts with traditional review formats and seeks to identify questions agreed to be both important and feasibly addressed by focused research projects.
A shortlist of 100 questions is presented with supporting text to provide perspective.
The article is intended to stimulate new and ongoing research on helminth infections, in support of sustainable global livestock health and productivity.
Stem cell differentiation is guided by contact with the physical microenvironment, influence by both topography and mechanical properties of the matrix. In this study, the combined effect of ...substratum nano-topography and mechanical stiffness in directing mesenchymal stem cell (MSC) chondrogenesis was investigated. Three polyesters of varying stiffness were thermally imprinted to create nano-grating or pillar patterns of the same dimension. The surface of the nano-patterned substrate was coated with chondroitin sulfate (CS) to provide an even surface chemistry, with cell-adhesive and chondro-inductive properties, across all polymeric substrates. The surface characteristic, mechanical modulus, and degradation of the CS-coated patterned polymeric substrates were analyzed. The cell morphology adopted on the nano-topographic surfaces were accounted by F-actin distribution, and correlated to the cell proliferation and chondrogenic differentiation outcomes. Results show that substratum stiffness and topographical cues affected MSC morphology and aggregation, and influenced the phenotypic development at the earlier stage of chondrogenic differentiation. Hyaline-like cartilage with middle/deep zone cartilage characteristics was generated on softer pillar surface, while on stiffer nano-pillar material MSCs showed potential to generate constituents of hyaline/fibro/hypertrophic cartilage. Fibro/superficial zone-like cartilage could be derived from nano-grating of softer stiffness, while stiffer nano-grating resulted in insignificant chondrogenesis. This study demonstrates the possibility of refining the phenotype of cartilage generated from MSCs by manipulating surface topography and material stiffness.
Pulse electromagnetic fields (PEMFs) have been shown to recruit calcium-signaling cascades common to chondrogenesis. Here we document the effects of specified PEMF parameters over mesenchymal stem ...cells (MSC) chondrogenic differentiation. MSCs undergoing chondrogenesis are preferentially responsive to an electromagnetic efficacy window defined by field amplitude, duration and frequency of exposure. Contrary to conventional practice of administering prolonged and repetitive exposures to PEMFs, optimal chondrogenic outcome is achieved in response to brief (10 minutes), low intensity (2 mT) exposure to 6 ms bursts of magnetic pulses, at 15 Hz, administered only once at the onset of chondrogenic induction. By contrast, repeated exposures diminished chondrogenic outcome and could be attributed to calcium entry after the initial induction. Transient receptor potential (TRP) channels appear to mediate these aspects of PEMF stimulation, serving as a conduit for extracellular calcium. Preventing calcium entry during the repeated PEMF exposure with the co-administration of EGTA or TRP channel antagonists precluded the inhibition of differentiation. This study highlights the intricacies of calcium homeostasis during early chondrogenesis and the constraints that are placed on PEMF-based therapeutic strategies aimed at promoting MSC chondrogenesis. The demonstrated efficacy of our optimized PEMF regimens has clear clinical implications for future regenerative strategies for cartilage.
Abstract Background The posterior tibial slope (PTS) is an important consideration in knee arthroplasty. However, there is still no consensus for the optimal slope. The objectives of this study were ...(1) to reliably determine the native PTS in this population using 3-dimensional computed tomography scans and (2) to determine the normal reference range for PTS in this population. Methods One hundred computed tomography scans of disease-free knees were analyzed. A 3-dimensional reconstructed image of the tibia was generated and aligned to its anatomic axis in the coronal and sagittal planes. The tibia was then rotationally aligned to the tibial plateau (tibial centroid axis) and PTS was measured from best-fit planes on the surface of the proximal tibia and individually for the medial and lateral plateaus. This was then repeated with the tibia rotationally aligned to the ankle (transmalleolar axis). Results When rotationally aligned to the tibial plateau, the mean PTS, medial PTS, and lateral PTS were 11.2° ± 3.0 (range, 4.7°-17.7°), 11.3° ± 3.2 (range, 2.7°-19.7°), and 10.9° ± 3.7 (range, 3.5°-19.4°), respectively. When rotationally aligned to the ankle, the mean PTS, medial PTS, and lateral PTS were 11.4° ± 3.0 (range, 5.3°-19.3°), 13.9° ± 3.7 (range, 3.1°-24.4°), and 9.7° ± 3.6 (range, 0.8°-17.7°), respectively. Conclusion The PTS in the normal Asian knee is on average 11° (mean) with a reference range of 5°-17° (mean ± 2 standard deviation). This has implications to surgery and implant design.
Background:
There is clinical and experimental evidence for altered adenosine signalling in the fetoplacental circulation in pregnancies complicated by diabetes, leading to adenosine accumulation in ...the placenta. However, the consequence for fetoplacental vasocontractility is unclear. This study examined contractility to adenosine of chorionic vessels from type 1 diabetes mellitus, gestational diabetes mellitus and normal pregnancies.
Methods:
Chorionic arteries and veins were isolated from human placenta from normal, gestational diabetes mellitus and type 1 diabetes mellitus pregnancies. Isometric tension recording measured responses to adenosine and the thromboxane A2 analogue U46619 (thromboxane A2 mediates fetoplacental vasoconstriction to adenosine). Adenosine and thromboxane prostanoid receptor protein expression was determined by immunoblotting.
Results:
Adenosine elicited contractions in chorionic arteries and veins which were impaired in both gestational diabetes mellitus and type 1 diabetes mellitus. Contractions to potassium chloride were unchanged. Adenosine A2A and A2B receptor protein levels were not different in gestational diabetes mellitus and normal pregnancies. Contractions to U46619 were unaltered in gestational diabetes mellitus arteries and increased in type 1 diabetes mellitus arteries. Overnight storage of vessels restored contractility to adenosine in gestational diabetes mellitus arteries and normalized contraction to U46619 in type 1 diabetes mellitus arteries.
Conclusion:
These data are consistent with the concept of aberrant adenosine signalling in diabetes; they show for the first time that this involves impaired adenosine contractility of the fetoplacental vasculature.
Osteoarthritis (OA) contributes to significant medical and socioeconomic burden in many populations. Its prevalence is expected to rise continuously owing to the combined effects of aging and ...increase in risk factors, including obesity, physical inactivity, and joint injuries. Pain is a hallmark presentation of OA. Topical nonsteroidal anti‐inflammatory drugs (NSAIDs) are recommended by many international guidelines as an early treatment option of the management of osteoarthritic pain. However, the use of topical NSAIDs remains low in Malaysia and appears not to be a preferred agent in managing OA pain by prescribers. There is also limited guidance from local medical bodies on the use of topical NSAIDs to manage OA pain. This consensus recommendation is intended to serve as a practical guide for healthcare practitioners on the use of topical NSAIDs in the management of OA pain. Eight statements and recommendations were finalized covering the areas of OA burden, topical NSAIDs formulations, safety and efficacy of topical NSAIDs, and patient education. Robust evidence is available to support the efficacy and safety of topical NSAIDs, with its benefits further strengthened by ease of use and access. Taking these into consideration, we recommend that healthcare practitioners advocate for the early use of topical NSAIDs over oral NSAIDs for mild‐to‐moderate OA pain, while engaging in a shared decision‐making process with patients for optimal clinical outcomes.
The role for mechanical stimulation in the control of cell fate has been previously proposed, suggesting that there may be a role of mechanical conditioning in directing mesenchymal stromal cells ...(MSCs) towards specific lineage for tissue engineering applications. Although previous studies have reported that calcium signalling is involved in regulating many cellular processes in many cell types, its role in managing cellular responses to tensile loading (mechanotransduction) of MSCs has not been fully elucidated. In order to establish this, we disrupted calcium signalling by blocking stretch-activated calcium channel (SACC) in human MSCs (hMSCs) in vitro. Passaged-2 hMSCs were exposed to cyclic tensile loading (1 Hz + 8% for 6, 24, 48, and 72 hours) in the presence of the SACC blocker, gadolinium. Analyses include image observations of immunochemistry and immunofluorescence staining from extracellular matrix (ECM) production, and measuring related tenogenic and apoptosis gene marker expression. Uniaxial tensile loading increased the expression of tenogenic markers and ECM production. However, exposure to strain in the presence of 20 μM gadolinium reduced the induction of almost all tenogenic markers and ECM staining, suggesting that SACC acts as a mechanosensor in strain-induced hMSC tenogenic differentiation process. Although cell death was observed in prolonged stretching, it did not appear to be apoptosis mediated. In conclusion, the knowledge gained in this study by elucidating the role of calcium in MSC mechanotransduction processes, and that in prolonged stretching results in non-apoptosis mediated cell death may be potential useful for regenerative medicine applications.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Meat represents an important part of the diet for many adults, supplying essential amino acids and micronutrients. However, high red and processed meat (RPM) intake is implicated in the development ...of cardiovascular disease and dyslipidemia. This study aimed to reduce RPM consumption in healthy, non-obese omnivores (21-48 years), who ate RPM ≥4 times per week, and to investigate its effect on cardiovascular risk factors using a single-group longitudinal study design (comprising an initial 4-week baseline period, followed by a 12-week intervention). Participants (16M : 21F) were assessed before (BL) and after (T0) the pre-intervention period and before (T0), at week 6 (T6) and at the end of intervention (T12). In a subset (8M : 15F), haematological parameters were measured at BL, T6 and T12. Compared with BL, protein intake from RPM reduced by 67% at T6 and 47% at T12 (4-day dietary records). BMI, body fat mass, and blood pressure did not change over the intervention in the whole cohort, but mean total, LDL and HDL cholesterol were reduced in males at T12 (effect sizes −0.52, −0.41 and −0.15 mmol l
−1
, respectively; each
P
< 0.01), with no change in total : HDL ratio observed. In the study sub-set, haemoglobin concentration, plus red and white cell count fell during the intervention (estimated effect size
ηp
2
0.300, 0.301 and 0.354, respectively; each
P
< 0.001). It was possible for omnivores to approximately halve their RPM intake, and in males this dietary change appeared to reduce blood lipid concentrations. However, acute dietary changes to RPM intake may have had an unfavourable impact on haematological parameters.
Reductions in red meat intake lowered LDL in men, but may have unfavourable short term impact on blood cell numbers.
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