Clavicular stress fracture in a cricket fast bowler: A case report

<p>Abstract</p> <p>Introduction</p> <p>Whilst rare, stress fractures of the clavicle have been described in other sports. To our knowledge, this is the first reported case of a stress fracture of the clavicle occurring in a cricket fast bowler.</p> <p>Case presentation</p> <p>A 23-year-old professional cricket fast bowler presented with activity related shoulder pain. Imaging demonstrated a stress fracture of the lateral third of the clavicle. This healed with rest and rehabilitation allowing a full return to professional sport.</p> <p>Conclusion</p> <p>This injury is treated with activity modification and technique adaptation. In a professional sportsman, this needs to be recognised early so that return to play can be as quick as possible.</p

Mutuality as a method: advancing a social paradigm for global mental health through mutual learning.

PURPOSE: Calls for "mutuality" in global mental health (GMH) aim to produce knowledge more equitably across epistemic and power differences. With funding, convening, and publishing power still concentrated in institutions in the global North, efforts to decolonize GMH emphasize the need for mutual learning instead of unidirectional knowledge transfers. This article reflects on mutuality as a concept and practice that engenders sustainable relations, conceptual innovation, and queries how epistemic power can be shared. METHODS: We draw on insights from an online mutual learning process over 8 months between 39 community-based and academic collaborators working in 24 countries. They came together to advance the shift towards a social paradigm in GMH. RESULTS: Our theorization of mutuality emphasizes that the processes and outcomes of knowledge production are inextricable. Mutual learning required an open-ended, iterative, and slower paced process that prioritized trust and remained responsive to all collaborators' needs and critiques. This resulted in a social paradigm that calls for GMH to (1) move from a deficit to a strength-based view of community mental health, (2) include local and experiential knowledge in scaling processes, (3) direct funding to community organizations, and (4) challenge concepts, such as trauma and resilience, through the lens of lived experience of communities in the global South. CONCLUSION: Under the current institutional arrangements in GMH, mutuality can only be imperfectly achieved. We present key ingredients of our partial success at mutual learning and conclude that challenging existing structural constraints is crucial to prevent a tokenistic use of the concept

Mutuality as a method: advancing a social paradigm for global mental health through mutual learning

Purpose: Calls for “mutuality” in global mental health (GMH) aim to produce knowledge more equitably across epistemic and power differences. With funding, convening, and publishing power still concentrated in institutions in the global North, efforts to decolonize GMH emphasize the need for mutual learning instead of unidirectional knowledge transfers. This article reflects on mutuality as a concept and practice that engenders sustainable relations, conceptual innovation, and queries how epistemic power can be shared. // Methods: We draw on insights from an online mutual learning process over 8 months between 39 community-based and academic collaborators working in 24 countries. They came together to advance the shift towards a social paradigm in GMH. // Results: Our theorization of mutuality emphasizes that the processes and outcomes of knowledge production are inextricable. Mutual learning required an open-ended, iterative, and slower paced process that prioritized trust and remained responsive to all collaborators’ needs and critiques. This resulted in a social paradigm that calls for GMH to (1) move from a deficit to a strength-based view of community mental health, (2) include local and experiential knowledge in scaling processes, (3) direct funding to community organizations, and (4) challenge concepts, such as trauma and resilience, through the lens of lived experience of communities in the global South. // Conclusion: Under the current institutional arrangements in GMH, mutuality can only be imperfectly achieved. We present key ingredients of our partial success at mutual learning and conclude that challenging existing structural constraints is crucial to prevent a tokenistic use of the concept

AMPK activation protects against diet induced obesity through Ucp1-independent thermogenesis in subcutaneous white adipose tissue

Obesity results from a chronic imbalance between energy intake and energy output but remains difficult to prevent or treat in humans. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an important regulator of energy homeostasis1,2,3 and is a molecular target of drugs used for the treatment of metabolic diseases, including obesity4,5. Here we show that mice expressing a gain-of-function AMPK mutant6 display a change in morphology of subcutaneous white adipocytes that is reminiscent of browning. However, despite a dramatic increase in mitochondrial content, Ucp1 expression is undetectable in these adipocytes. In response to a high-fat diet (HFD), expression of skeletal muscle–associated genes is induced in subcutaneous white adipocytes from the gain-of-function AMPK mutant mice. Chronic genetic AMPK activation results in protection against diet-induced obesity due to an increase in whole-body energy expenditure, most probably because of a substantial increase in the oxygen consumption rate of white adipose tissue. These results suggest that AMPK activation enriches, or leads to the emergence of, a population of subcutaneous white adipocytes that produce heat via Ucp1-independent uncoupling of adenosine triphosphate (ATP) production on a HFD. Our findings indicate that AMPK activation specifically in adipose tissue may have therapeutic potential for the treatment of obesity

cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites

Genome-level homology and phylogeny of Shewanella (Gammaproteobacteria: lteromonadales: Shewanellaceae)

<p>Abstract</p> <p>Background</p> <p>The explosion in availability of whole genome data provides the opportunity to build phylogenetic hypotheses based on these data as well as the ability to learn more about the genomes themselves. The biological history of genes and genomes can be investigated based on the taxomonic history provided by the phylogeny. A phylogenetic hypothesis based on complete genome data is presented for the genus <it>Shewanella </it>(Gammaproteobacteria: Alteromonadales: Shewanellaceae). Nineteen taxa from <it>Shewanella </it>(16 species and 3 additional strains of one species) as well as three outgroup species representing the genera <it>Aeromonas </it>(Gammaproteobacteria: Aeromonadales: Aeromonadaceae), <it>Alteromonas </it>(Gammaproteobacteria: Alteromonadales: Alteromonadaceae) and <it>Colwellia </it>(Gammaproteobacteria: Alteromonadales: Colwelliaceae) are included for a total of 22 taxa.</p> <p>Results</p> <p>Putatively homologous regions were found across unannotated genomes and tested with a phylogenetic analysis. Two genome-wide data-sets are considered, one including only those genomic regions for which all taxa are represented, which included 3,361,015 aligned nucleotide base-pairs (bp) and a second that additionally includes those regions present in only subsets of taxa, which totaled 12,456,624 aligned bp. Alignment columns in these large data-sets were then randomly sampled to create smaller data-sets. After the phylogenetic hypothesis was generated, genome annotations were projected onto the DNA sequence alignment to compare the historical hypothesis generated by the phylogeny with the functional hypothesis posited by annotation.</p> <p>Conclusions</p> <p>Individual phylogenetic analyses of the 243 locally co-linear genome regions all failed to recover the genome topology, but the smaller data-sets that were random samplings of the large concatenated alignments all produced the genome topology. It is shown that there is not a single orthologous copy of 16S rRNA across the taxon sampling included in this study and that the relationships among the multiple copies are consistent with 16S rRNA undergoing concerted evolution. Unannotated whole genome data can provide excellent raw material for generating hypotheses of historical homology, which can be tested with phylogenetic analysis and compared with hypotheses of gene function.</p

Widespread Expression of BORIS/CTCFL in Normal and Cancer Cells

BORIS (CTCFL) is the paralog of CTCF (CCCTC-binding factor; NM_006565), a ubiquitously expressed DNA-binding protein with diverse roles in gene expression and chromatin organisation. BORIS and CTCF have virtually identical zinc finger domains, yet display major differences in their respective C- and N-terminal regions. Unlike CTCF, BORIS expression has been reported only in the testis and certain malignancies, leading to its classification as a “cancer-testis” antigen. However, the expression pattern of BORIS is both a significant and unresolved question in the field of DNA binding proteins. Here, we identify BORIS in the cytoplasm and nucleus of a wide range of normal and cancer cells. We compare the localization of CTCF and BORIS in the nucleus and demonstrate enrichment of BORIS within the nucleolus, inside the nucleolin core structure and adjacent to fibrillarin in the dense fibrillar component. In contrast, CTCF is not enriched in the nucleolus. Live imaging of cells transiently transfected with GFP tagged BORIS confirmed the nucleolar accumulation of BORIS. While BORIS transcript levels are low compared to CTCF, its protein levels are readily detectable. These findings show that BORIS expression is more widespread than previously believed, and suggest a role for BORIS in nucleolar function

Serotypes, virulence genes and intimin types of Shiga toxin (verocytotoxin)-producing Escherichia coli isolates from minced beef in Lugo (Spain) from 1995 through 2003

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) have emerged as pathogens that can cause food-borne infections and severe and potentially fatal illnesses in humans, such as haemorrhagic colitis (HC) and haemolytic uraemic syndrome (HUS). In Spain, like in many other countries, STEC strains have been frequently isolated from ruminants, and represent a significant cause of sporadic cases of human infection. In view of the lack of data on STEC isolated from food in Spain, the objectives of this study were to determine the level of microbiological contamination and the prevalence of STEC O157:H7 and non-O157 in a large sampling of minced beef collected from 30 local stores in Lugo city between 1995 and 2003. Also to establish if those STEC isolated from food possessed the same virulence profiles as STEC strains causing human infections. RESULTS: STEC were detected in 95 (12%) of the 785 minced beef samples tested. STEC O157:H7 was isolated from eight (1.0%) samples and non-O157 STEC from 90 (11%) samples. Ninety-six STEC isolates were further characterized by PCR and serotyping. PCR showed that 28 (29%) isolates carried stx(1 )genes, 49 (51%) possessed stx(2 )genes, and 19 (20%) both stx(1 )and stx(2). Enterohemolysin (ehxA) and intimin (eae) virulence genes were detected in 43 (45%) and in 25 (26%) of the isolates, respectively. Typing of the eae variants detected four types: γ1 (nine isolates), β1 (eight isolates), ε1 (three isolates), and θ (two isolates). The majority (68%) of STEC isolates belonged to serotypes previously detected in human STEC and 38% to serotypes associated with STEC isolated from patients with HUS. Ten new serotypes not previously described in raw beef products were also detected. The highly virulent seropathotypes O26:H11 stx(1 )eae-β1, O157:H7 stx(1)stx(2 )eae-γ1 and O157:H7 stx(2)eae-γ1, which are the most frequently observed among STEC causing human infections in Spain, were detected in 10 of the 96 STEC isolates. Furthermore, phage typing of STEC O157:H7 isolates showed that the majority (seven of eight isolates) belonged to the main phage types previously detected in STEC O157:H7 strains associated with severe human illnesses. CONCLUSION: The results of this study do not differ greatly from those reported in other countries with regard to prevalence of O157 and non-O157 STEC in minced beef. As we suspected, serotypes different from O157:H7 also play an important role in food contamination in Spain, including the highly virulent seropathotype O26:H11 stx(1 )eae-β1. Thus, our data confirm minced beef in the city of Lugo as vehicles of highly pathogenic STEC. This requires that control measures to be introduced and implemented to increase the safety of minced beef

Activity and expression of progesterone metabolizing 5α-reductase, 20α-hydroxysteroid oxidoreductase and 3α(β)-hydroxysteroid oxidoreductases in tumorigenic (MCF-7, MDA-MB-231, T-47D) and nontumorigenic (MCF-10A) human breast cancer cells

BACKGROUND: Recent observations indicate that human tumorous breast tissue metabolizes progesterone differently than nontumorous breast tissue. Specifically, 5α-reduced metabolites (5α-pregnanes, shown to stimulate cell proliferation and detachment) are produced at a significantly higher rate in tumorous tissue, indicating increased 5α-reductase (5αR) activity. Conversely, the activities of 3α-hydroxysteroid oxidoreductase (3α-HSO) and 20α-HSO enzymes appeared to be higher in normal tissues. The elevated conversion to 5α-pregnanes occurred regardless of estrogen (ER) or progesterone (PR) receptor levels. To gain insight into these differences, the activities and expression of these progesterone converting enzymes were investigated in a nontumorigenic cell line, MCF-10A (ER- and PR-negative), and the three tumorigenic cell lines, MDA-MB-231 (ER- and PR-negative), MCF-7 and T-47D (ER- and PR-positive). METHODS: For the enzyme activity studies, either whole cells were incubated with [(14)C]progesterone for 2, 4, 8, and 24 hours, or the microsomal/cytosolic fraction was incubated for 15–60 minutes with [(3)H]progesterone, and the metabolites were identified and quantified. Semi-quantitative RT-PCR was employed to determine the relative levels of expression of 5αR type1 (SRD5A1), 5αR type 2 (SRD5A2), 20α-HSO (AKR1C1), 3α-HSO type 2 (AKR1C3), 3α-HSO type 3 (AKR1C2) and 3β-HSO (HSD3B1/HSD3B2) in the four cell lines using 18S rRNA as an internal control. RESULTS: The relative 5α-reductase activity, when considered as a ratio of 5α-pregnanes/4-pregnenes, was 4.21 (± 0.49) for MCF-7 cells, 6.24 (± 1.14) for MDA-MB-231 cells, 4.62 (± 0.43) for T-47D cells and 0.65 (± 0.07) for MCF-10A cells, constituting approximately 6.5-fold, 9.6-fold and 7.1 fold higher conversion to 5α-pregnanes in the tumorigenic cells, respectively, than in the nontumorigenic MCF-10A cells. Conversely, the 20α-HSO and 3α-HSO activities were significantly higher (p < 0.001) in MCF-10A cells than in the other three cell types. In the MCF-10A cells, 20α-HSO activity was 8-14-fold higher and the 3α-HSO activity was 2.5-5.4-fold higher than in the other three cell types. The values of 5αR:20α-HSO ratios were 16.9 – 32.6-fold greater and the 5αR:3α-HSO ratios were 5.2 – 10.5-fold greater in MCF-7, MDA-MB-231 and T-47D cells than in MCF-10A cells. RT-PCR showed significantly higher expression of 5αR1 (p < 0.001), and lower expression of 20α-HSO (p < 0.001), 3α-HSO2 (p < 0.001), 3α-HSO3 (p < 0.001) in MCF-7, MDA-MB-231 and T-47D cells than in MCF-10A cells. CONCLUSION: The findings provide the first evidence that the 5αR activity (leading to the conversion of progesterone to the cancer promoting 5α-pregnanes) is significantly higher in the tumorigenic MCF-7, MDA-MB-231 and T-47D breast cell lines than in the nontumorigenic MCF-10A cell line. The higher 5αR activity coincides with significantly greater expression of 5αR1. On the other hand, the activities of 20α-HSO and 3α-HSO are higher in the MCF-10A cells than in MCF-7, MDA-MB-231 and T-47D cells; these differences in activity correlate with significantly higher expression of 20α-HSO, 3α-HSO2 and 3α-HSO3 in MCF-10A cells. Changes in progesterone metabolizing enzyme expression (resulting in enzyme activity changes) may be responsible for stimulating breast cancer by increased production of tumor-promoting 5α-pregnanes and decreased production of anti-cancer 20α – and 3α-4-pregnenes