Southern ocean carbon and heat impact on climate.

The Southern Ocean greatly contributes to the regulation of the global climate by controlling important heat and carbon exchanges between the atmosphere and the ocean. Rates of climate change on decadal timescales are therefore impacted by oceanic processes taking place in the Southern Ocean, yet too little is known about these processes. Limitations come both from the lack of observations in this extreme environment and its inherent sensitivity to intermittent processes at scales that are not well captured in current Earth system models. The Southern Ocean Carbon and Heat Impact on Climate programme was launched to address this knowledge gap, with the overall objective to understand and quantify variability of heat and carbon budgets in the Southern Ocean through an investigation of the key physical processes controlling exchanges between the atmosphere, ocean and sea ice using a combination of observational and modelling approaches. Here, we provide a brief overview of the programme, as well as a summary of some of the scientific progress achieved during its first half. Advances range from new evidence of the importance of specific processes in Southern Ocean ventilation rate (e.g. storm-induced turbulence, sea-ice meltwater fronts, wind-induced gyre circulation, dense shelf water formation and abyssal mixing) to refined descriptions of the physical changes currently ongoing in the Southern Ocean and of their link with global climate. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.

Broad responses and attitudes to having music in surgery (the BRAHMS study) - a South African perspective.

BACKGROUND: Music is played in operating theatres (OTs) throughout the world, though controversy around its use exists. While some clinicians may find background music favourable to the theatre mood and a way to augment surgical performance, there is concern raised over its distracting and noise-creating properties. METHODS: In this prospective observational study, between August and December 2021, 110 surgeons and registrars in South Africa responded to a survey investigating the way they use music, and their perceptions and attitudes towards its effect on the OT environment. RESULTS: In this cohort, 66% were male, 29% were consultants and the most common age range was 30-39 years old. Eighty per cent of respondents reported that music was played at least "sometimes", with 74% reporting that they enjoyed it. Easy Listening was the most played and preferred genre followed by Top 40/Billboard hits. Overwhelmingly, respondents reported that background music in the OT improved temperament, focus, mood, and performance, though over a quarter felt it worsened communication. Thirty-one per cent of respondents reported that the choice of music depended on the type of operation, and 70% would turn music down or off during crises. Those who enjoyed music in their spare time were significantly more likely to enjoy music in the OT and perceive it positively. CONCLUSION: This study provides a window into the surgeons' use of and attitudes to intraoperative music in South Africa. While overall, music is viewed positively by this cohort, some concerns remain regarding communication and distractedness. Further interventional and qualitative studies would be useful.

Soluble ECM promotes organotypic formation in lung alveolar model.

Micropatterned suspension culture creates consistently sized and shaped cell aggregates but has not produced organotypic structures from stable cells, thus restricting its use in accurate disease modeling. Here, we show that organotypic structure is achieved in hybrid suspension culture via supplementation of soluble extracellular matrix (ECM). We created a viable lung organoid from epithelial, endothelial, and fibroblast human stable cell lines in suspension culture. We demonstrate the importance of soluble ECM in organotypic patterning with the emergence of lumen-like structures with airspace showing feasible gas exchange units, formation of branching, perfusable vasculature, and long-term 70-day maintenance of lumen structure. Our results show a dependent relationship between enhanced fibronectin fibril assembly and the incorporation of ECM in the organoid. We successfully applied this technology in modeling lung fibrosis via bleomycin induction and test a potential antifibrotic drug in vitro while maintaining fundamental cell-cell interactions in lung tissue. Our human fluorescent lung organoid (hFLO) model represents features of pulmonary fibrosis which were ameliorated by fasudil treatment. We also demonstrate a 3D culture method with potential of creating organoids from mature cells, thus opening avenues for disease modeling and regenerative medicine, enhancing understanding of lung cell biology in health and lung disease.

A split-tattoo randomized Q-switched neodymium-doped yttrium-aluminium-garnet laser trial comparing the efficacy of a novel three-pass, one-session method with a conventional method in the treatment of blue/black tattoos in darker skin types.

Tattoos with blue/black ink show good lightening of pigment after treatment with 1064 nm Q-switched (QS) neodymium-doped yttrium-aluminium-garnet (Nd:YAG) laser. In this randomized trial, we compared the efficacy of a novel three pass, one session procedure (R15 method) with a conventional method for treating blue/black tattoos in darker skin types. Tattoos were treated with 1064 nm QS Nd:YAG Laser with a spot size of 4 mm, fluence of 5 J/cm2 and frequency of 5 Hz. The tattoo pigment lightening was comparable with both methods. Thread-like tattoos had significantly better pigment lightening with fewer side effects than the broad band-like tattoos. We would like to recommend the R15 method of the QS Nd:YAG laser for thread-like tattoos, which can save patients' time, cut short the frequency of their hospital visits and, more importantly, decrease the cost involved in it.

Dual-energy CT-generated bone marrow oedema maps improve timely visualisation and recognition of acute lower extremity fractures.

AIM: To assesses whether utilising bone marrow oedema (BMO) maps improved fracture read times and reader confidence in a large series of acute lower extremity trauma dual-energy computed tomography (DECT) studies. MATERIALS AND METHODS: One hundred and six DECT studies, including 60 fracture cases and 46 non-fracture cases, were evaluated retrospectively in this cross-sectional study. Three-dimensional (3D) BMO maps were generated for each study and coded to display skeletal anatomy in blue and marrow oedema in green. Studies were interpreted by two readers in two timed stages (without and with BMO maps). Readers identified the number, anatomical location, and comminution of fractures. Reader confidence (five-point Likert scale) for fracture identification and anatomical regions where oedema was present was also recorded. RESULTS: Decreased read times (p<0.01) were observed when readers utilised BMO maps for their fracture search. The presence of oedema on BMO maps corresponded with associated fracture in 75.7% reads. No differences in reader confidence were observed as a result of using this BMO-guided technique (>95%, 5/5 for both readers with and without the aid of BMO maps). CONCLUSIONS: DECT BMO maps improve the speed of radiological identification of suspected acute lower extremity fractures with preserved reader confidence. It may help emergent detection of fractures, important for patient management and outcomes.

qSR: a quantitative super-resolution analysis tool reveals the cell-cycle dependent organization of RNA Polymerase I in live human cells.

We present qSR, an analytical tool for the quantitative analysis of single molecule based super-resolution data. The software is created as an open-source platform integrating multiple algorithms for rigorous spatial and temporal characterizations of protein clusters in super-resolution data of living cells. First, we illustrate qSR using a sample live cell data of RNA Polymerase II (Pol II) as an example of highly dynamic sub-diffractive clusters. Then we utilize qSR to investigate the organization and dynamics of endogenous RNA Polymerase I (Pol I) in live human cells, throughout the cell cycle. Our analysis reveals a previously uncharacterized transient clustering of Pol I. Both stable and transient populations of Pol I clusters co-exist in individual living cells, and their relative fraction vary during cell cycle, in a manner correlating with global gene expression. Thus, qSR serves to facilitate the study of protein organization and dynamics with very high spatial and temporal resolutions directly in live cell.

HR-TEM and FT-Raman dataset of the caffeine interacted Phe-Phe peptide nanotube for possible sensing applications.

Sensing ability of caffeine interaction with Phe-Phe annotates (PNTs), is presented (Govindhan et al., 2017; Karthikeyan et al., 2014; Tavagnacco et al., 2013; Kennedy et al., 2011; Wang et al., 2017) [1-5] in this data set. Investigation of synthesized caffeine carrying peptide nanotubes are carried out by FT-Raman spectral analysis and high resolution transmission electron microscopy (HR-TEM). Particle size of the caffeine loaded PNTs is < 40 nm. The FT-Raman spectrum signals are enhanced in the region of 400-1700 cm-1. These data are ideal tool for the applications like biosensing and drug delivery research (DDS).

LR8 Expression in fibroblasts of healthy and fibrotic human tissues.

LR8 gene was first reported in a subpopulation of cultured human lung fibroblasts expressing the receptor for C1q-globular domain, and it was not detectable in cultured endothelial cells and smooth muscle cells. LR8 mRNA levels were higher in fibrotic lungs. In this study we assessed LR8 production in human tissues and determined if the distribution of fibroblasts producing LR8 is affected in fibrosis. Normal and fibrotic tissue sections from human liver, lung and kidneys were immunostained with antibodies to LR8 and examined for the presence of fibroblasts staining positively and negatively. The cells were also examined for co-expression of α-smooth muscle actin (SMA), a marker for myofibroblasts. The results showed that LR8 was expressed by fibroblasts, smooth muscle cells, endothelial cells, bile duct cells, pulmonary alveolar cells and distal and proximal kidney tubule cells. Connective tissues of normal and fibrotic tissues contained fibroblasts staining positively and negatively with anti- LR8 antibody. The number of LR8-positive cells was higher in fibrotic tissues, but differences were not statistically significant. Fibroblasts producing both LR8 and SMA were present in higher numbers in fibrotic tissues as compared to normal tissues and the differences were statistically significant (p<0.05). Our results show that fibroblast subtypes differing in LR8 expression are present in human tissues, and that in fibrotic tissues cells co-expressing LR8 and SMA are present. Our results indicate that LR8 expressing cells may participate in the early stages of fibrotic diseases and that fibroblasts expressing LR8, not LR8 negative cells, have potential to become myofibroblasts in fibrotic tissues.

Regulating dynamic signaling between hematopoietic stem cells and niche cells via a hydrogel matrix.

Hematopoietic stem cells (HSC) reside in unique bone marrow niches and are influenced by signals from surrounding cells, the extracellular matrix (ECM), ECM-bound or diffusible biomolecules. Here we describe the use of a three-dimensional hydrogel to alter the balance of HSC-generated autocrine feedback and paracrine signals generated by co-cultured niche-associated cells. We report shifts in HSC proliferation rate and fate specification in the presence of lineage positive (Lin+) niche cells. Hydrogels promoting autocrine feedback enhanced expansion of early hematopoietic progenitors while paracrine signals from Lin+ cells increased myeloid differentiation. We report thresholds where autocrine vs. paracrine cues alter HSC fate transitions, and were able to selectively abrogate the effects of matrix diffusivity and niche cell co-culture via the use of inhibitory cocktails of autocrine or paracrine signals. Together, these results suggest diffusive biotransport in three-dimensional biomaterials are a critical design element for the development of a synthetic stem cell niche.

Assessment of resuscitation as measured by markers of metabolic acidosis and features of injury.

AIMS: The best time for definitive orthopaedic care is often unclear in patients with multiple injuries. The objective of this study was make a prospective assessment of the safety of our early appropriate care (EAC) strategy and to evaluate the potential benefit of additional laboratory data to determine readiness for surgery. PATIENTS AND METHODS: A cohort of 335 patients with fractures of the pelvis, acetabulum, femur, or spine were included. Patients underwent definitive fixation within 36 hours if one of the following three parameters were met: lactate < 4.0 mmol/L; pH ≥ 7.25; or base excess (BE) ≥ -5.5 mmol/L. If all three parameters were met, resuscitation was designated full protocol resuscitation (FPR). If less than all three parameters were met, it was designated an incomplete protocol resuscitation (IPR). Complications were assessed by an independent adjudication committee and included infection; sepsis; PE/DVT; organ failure; pneumonia, and acute respiratory distress syndrome (ARDS). RESULTS: In total, 66 patients (19.7%) developed 90 complications. An historical cohort of 1441 patients had a complication rate of 22.1%. The complication rate for patients with only one EAC parameter at the point of protocol was 34.3%, which was higher than other groups (p = 0.041). Patients who had IPR did not have significantly more complications (31.8%) than those who had FPR (22.6%; p = 0.078). Regression analysis showed male gender and injury severity score to be independent predictors of complications. CONCLUSIONS: This study highlights important trends in the IPR and FPR groups, suggesting that differences in resuscitation parameters may guide care in certain patients; further study is, however, required. We advocate the use of the existing protocol, while research is continued for high-risk subgroups. Cite this article: Bone Joint J 2017;99-B:122-7.

Oral supplementation of trans-cinnamaldehyde reduces uropathogenic Escherichia coli colonization in a mouse model.

Urinary tract infections (UTIs) in the United States result in more than 7 million hospital visits per year. Uropathogenic Escherichia coli (UPEC) is responsible for more than 80% of UTIs. Although antibiotics are the drug of choice to control UTIs, their repeated use has resulted in the emergence of antibiotic-resistant UPEC. Thus, there is a need for effective alternate strategies to control UPEC infections. This study investigated the efficacy of trans-cinnamaldehyde (TC), a food-grade molecule present in cinnamon, in reducing UPEC colonization and pathogenesis in the lower UTI. Female C57BL/6 mice (6-8 weeks old) were fed ad libitum with 0, 0·1, 0·2 and 0·4% TC containing mouse chow for 10 days. Following TC supplementation, animals were experimentally infected with UPEC by transurethral catheterization. Mice were euthanized on days 1, 2 and 4 postinfection, and the bladder, urethra and urine were collected for bacterial enumeration. Prophylactic TC supplementation significantly (P ≤ 0·05) reduced UPEC colonization in the urinary bladder and urethra compared to the control. Results indicate that TC could potentially be used as an oral supplement to control UPEC-associated lower UTIs, however, follow-up clinical trials are warranted. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we have demonstrated that oral supplementation of trans-cinnamaldehyde (TC) reduced uropathogenic Escherichia coli (UPEC)-associated lower urinary tract infection (UTI) in mice. Specifically, in-feed supplementation of TC significantly decreased UPEC populations in the urethra and bladder, thereby reducing the infectious load. These findings are particularly significant given the increase in incidence and prevalence of antibiotic-resistant UTIs. Our study offers new insights into the potential use of natural antimicrobials including TC, the active ingredient in cinnamon, as a nonantibiotic-based natural dietary intervention in the prophylaxis of lower UTIs.

Population Pharmacokinetics and Pharmacodynamics of the Calcimimetic Etelcalcetide in Chronic Kidney Disease and Secondary Hyperparathyroidism Receiving Hemodialysis.

Etelcalcetide is a novel calcimimetic in development for the treatment of secondary hyperparathyroidism (SHPT). A population pharmacokinetic/pharmacodynamic (PK/PD) model was developed relating etelcalcetide exposures to markers of efficacy (parathyroid hormone [PTH]) and safety (calcium) using data from three clinical studies. The semimechanistic model was developed that included allosteric activation pharmacology and understanding of calcium homeostasis. The temporal profiles for all biomarkers were well described by the model. The cooperativity constant was 4.94, confirming allosteric activation mechanism. Subjects with more severe disease (higher PTH baseline) were predicted to experience less pronounced reduction in PTH (percentage change from baseline), but more reduction in calcium (Ca; percentage change from baseline). There was no evidence that dose adjustment by any covariate was needed. Model-based simulations provided quantitative support to several elements of dosing, such as starting dose, monitoring, and titration timing for registration trials.

Development and initial validation of the Cat HEalth and Wellbeing (CHEW) Questionnaire: a generic health-related quality of life instrument for cats.

OBJECTIVES: The aims of the study were to define factors that owners consider relevant to the health-related quality of life (HRQoL) of cats, to develop an instrument based on this information, and to evaluate the validity and reliability of the final instrument (the Cat HEalth and Wellbeing [CHEW] Questionnaire). METHODS: Psychometric research techniques and guidance from the US Food and Drug Administration on outcome measures were used to develop a valid and reliable instrument. Fifty-four cat owners and caregivers participated in the qualitative research, while 1303 cat owners were included in the quantitative validation phase (development dataset, n = 648; validation dataset, n = 655). A random subset of cat owners (n = 391) also participated in test-retest evaluation. Qualitative research was used to generate a draft instrument, which was then subjected to quantitative validation techniques. These included item reduction, domain identification, data quality assessment, and exploratory and confirmatory analysis to develop a final instrument, which underwent confirmatory reliability and validity assessment. RESULTS: A draft instrument with 11 domains and 100 items based on qualitative research underwent online quantitative validation testing which refined the instrument to eight domains and 33 items. Confirmatory reliability and validity assessment showed that the final instrument had good validity, was able to discriminate between cats by age and overall health status, and demonstrated good internal and test-retest reliability. CONCLUSIONS AND RELEVANCE: The CHEW Questionnaire was developed and validated. Additional research is needed to verify its ability to differentiate cats with and without disease, and to assess its potential as a screening tool.

Inaccessible Masturbation, Impossible Mourning: Collective Melancholia, the Prohibition on Female Sexual Subjects in India, and Masturbation Fantasy as a Zone of the Strange.

This paper explores a subjective experience-and identification-that a cohort of Indian women identifies as "home." This experience of "home" provides an attachment to a collective melancholia that keeps in place a prohibited female sexual subjectivity. The paper provides a brief historical overview of the prohibition of female sexual subjectivity and erotic agency in India. Following this, it discusses women's masturbation fantasies that illustrate the toggle between women's permitted and prohibited identifications. A clinical case example is presented to illustrate the hopelessness and mourning inherent in the psychoanalytic journey into subjectivity, a journey involving a departure from a shared cultural history.

Dichotomy between the Hole and Electron Behavior in Multiband Superconductor FeSe Probed by Ultrahigh Magnetic Fields.

Magnetoresistivity ρ(xx) and Hall resistivity ρ(xy) in ultrahigh magnetic fields up to 88 T are measured down to 0.15 K to clarify the multiband electronic structure in high-quality single crystals of superconducting FeSe. At low temperatures and high fields we observe quantum oscillations in both resistivity and the Hall effect, confirming the multiband Fermi surface with small volumes. We propose a novel approach to identify from magnetotransport measurements the sign of the charge carriers corresponding to a particular cyclotron orbit in a compensated metal. The observed significant differences in the relative amplitudes of the quantum oscillations between the ρ(xx) and ρ(xy) components, together with the positive sign of the high-field ρ(xy), reveal that the largest pocket should correspond to the hole band. The low-field magnetotransport data in the normal state suggest that, in addition to one hole and one almost compensated electron band, the orthorhombic phase of FeSe exhibits an additional tiny electron pocket with a high mobility.

Linear magnetoresistance caused by mobility fluctuations in n-doped Cd(3)As(2).

Cd(3)As(2) is a candidate three-dimensional Dirac semimetal which has exceedingly high mobility and nonsaturating linear magnetoresistance that may be relevant for future practical applications. We report magnetotransport and tunnel diode oscillation measurements on Cd(3)As(2), in magnetic fields up to 65 T and temperatures between 1.5 and 300 K. We find that the nonsaturating linear magnetoresistance persists up to 65 T and it is likely caused by disorder effects, as it scales with the high mobility rather than directly linked to Fermi surface changes even when approaching the quantum limit. From the observed quantum oscillations, we determine the bulk three-dimensional Fermi surface having signatures of Dirac behavior with a nontrivial Berry phase shift, very light effective quasiparticle masses, and clear deviations from the band-structure predictions. In very high fields we also detect signatures of large Zeeman spin splitting (g∼16).

Takotsubo cardiomyopathy following electroconvulsive therapy: an increasingly recognised phenomenon.

Treatment of patients with severe depressive illnesses requiring electroconvulsive therapy (ECT) is challenging. This is compounded by the presence of physical comorbidities and potential complications. We report the case of a patient, on long-term bisoprolol, who developed acute epigastric pain and dyspnoea shortly after receiving ECT for treatment-refractory depression. An ECG showed new-onset ischaemic changes and a troponin-I level was elevated at 12 h. A diagnosis of Takotsubo cardiomyopathy was reached following angiography, which demonstrated left ventricular hypokinesia in the absence of coronary artery disease. With supportive treatment the patient made a good recovery. This report highlights the risk of developing Takotsubo cardiomyopathy following ECT despite ß-adrenergic receptor blockade, and adds to a growing number of cases reporting this complication. Clinicians involved in the care of patients undergoing ECT must be aware of this complication and should consider Takotsubo cardiomyopathy in patients who develop atypical chest pain after ECT.