Adaptation of sea turtles to climate warming: Will phenological responses be sufficient to counteract changes in reproductive output?

Sea turtles are vulnerable to climate change since their reproductive output is influenced by incubating temperatures, with warmer temperatures causing lower hatching success and increased feminization of embryos. Their ability to cope with projected increases in ambient temperatures will depend on their capacity to adapt to shifts in climatic regimes. Here, we assessed the extent to which phenological shifts could mitigate impacts from increases in ambient temperatures (from 1.5 to 3°C in air temperatures and from 1.4 to 2.3°C in sea surface temperatures by 2100 at our sites) on four species of sea turtles, under a "middle of the road" scenario (SSP2-4.5). Sand temperatures at sea turtle nesting sites are projected to increase from 0.58 to 4.17°C by 2100 and expected shifts in nesting of 26-43 days earlier will not be sufficient to maintain current incubation temperatures at 7 (29%) of our sites, hatching success rates at 10 (42%) of our sites, with current trends in hatchling sex ratio being able to be maintained at half of the sites. We also calculated the phenological shifts that would be required (both backward for an earlier shift in nesting and forward for a later shift) to keep up with present-day incubation temperatures, hatching success rates, and sex ratios. The required shifts backward in nesting for incubation temperatures ranged from -20 to -191 days, whereas the required shifts forward ranged from +54 to +180 days. However, for half of the sites, no matter the shift the median incubation temperature will always be warmer than the 75th percentile of current ranges. Given that phenological shifts will not be able to ameliorate predicted changes in temperature, hatching success and sex ratio at most sites, turtles may need to use other adaptive responses and/or there is the need to enhance sea turtle resilience to climate warming.

Experimental testing of a prototype cantilevered liquid-nitrogen-cooled silicon mirror.

This report presents testing of a prototype cantilevered liquid-nitrogen-cooled silicon mirror. This mirror was designed to be the first mirror for the new soft X-ray beamlines to be built as part of the Advanced Light Source Upgrade. Test activities focused on fracture, heat transfer, modal response and distortion, and indicated that the mirror functions as intended.

It was the best of times, it was the worst of times: a tale of two cities-Beijing and Shanghai-why the divergent COVID-19 control outcomes?

Coronavirus disease 2019 (COVID-19) both creates and complicates public health challenges. Yet, the pandemic also provides a unique lens for dissecting complex issues in global health that could benefit society in the long run. In this article, we discuss the underlying reasons that can help explain the divergent COVID-19 control outcomes between Beijing and Shanghai-two advanced metropolises that are similar in their municipal capacity, administrative capability and pandemic strategy. We hope insights from this investigation contribute to the development of disease prevention systems, such as context-specific and data-driven public health strategies that could yield optimal pandemic control outcomes with minimal unintended consequences, both amid and beyond COVID-19.

Propranolol versus steroids for the treatment of ulcerated infantile hemangiomas.

BACKGROUND: There has been a paradigm shift from steroids to propranolol for the pharmacologic treatment of infantile hemangiomas (IH); however, the outcomes for ulcerated IH are not well studied. The purpose of this study was to compare the efficacy of steroids and propranolol specifically for ulcerated IH. METHODS: A retrospective review was conducted on patients with ulcerated IH treated with propranolol or steroids at a single tertiary care institution between 2007 and 2014. Patient characteristics, hemangioma features, and outcomes, including time to heal and medication complications, were compared between propranolol and steroid patients. RESULTS: There were 29 patients treated with propranolol and 23 with steroids. There were no significant differences in the two treatment groups including age, race, sex, size, or insurance status. There were more head/neck IH in the steroid group. There was no significant difference in the percentage of healed lesions (93 vs. 74%, P = 0.12) or the median time to heal (80 vs. 126 days, p = 0.21) between groups. Overall complication rates also did not vary between medications (24 vs. 44%, P = 0.14). CONCLUSION: Propranolol is noninferior to steroids for the treatment of ulcerated IH; however, healing time is lengthy regardless of treatment. While side effect profiles differed between medications, the overall complication rate was similar.

Tumor-derived mural-like cells coordinate with endothelial cells: role of YKL-40 in mural cell-mediated angiogenesis.

Tumor neo-vasculature is characterized by spatial coordination of endothelial cells with mural cells, which delivers oxygen and nutrients. Here, we explored a key role of the secreted glycoprotein YKL-40, a mesenchymal marker, in the interaction between endothelial cells and mesenchymal mural-like cells for tumor angiogenesis. Xenotransplantation of tumor-derived mural-like cells (GSDCs) expressing YKL-40 in mice developed extensive and stable blood vessels covered with more GSDCs than those in YKL-40 gene knockdown tumors. YKL-40 expressed by GSDCs was associated with increased interaction of neural cadherin/ß-catenin/smooth muscle alpha actin; thus, mediating cell-cell adhesion and permeability. YKL-40 also induced the interaction of vascular endothelial cadherin/ß-catenin/actin in endothelial cells (HMVECs). In cell co-culture systems, YKL-40 enhanced both GSDC and HMVEC contacts, restricted vascular leakage, and stabilized vascular networks. Collectively, the data inform new mechanistic insights into the cooperation of mural cells with endothelial cells induced by YKL-40 during tumor angiogenesis, and also enhance our understanding of YKL-40 in both mural and endothelial cell biology.

Breast cancer expression of YKL-40 correlates with tumour grade, poor differentiation, and other cancer markers.

BACKGROUND: Serum levels of a secreted glycoprotein YKL-40 are elevated in patients with a wide range of cancers including breast, colorectal, and ovarian cancers. Furthermore, these increased levels correlate with poorer survival of cancer patients, suggesting that serum levels of YKL-40 might be a prognostic biomarker. However, the tissue expression of YKL-40 and its relationship with clinical outcomes and other potential markers are poorly understood. METHODS: Tissue samples from invasive breast cancers, breast ductal carcinoma in situ (DCIS), and cancer-free reduction mammoplasty were enrolled. YKL-40 expression was measured using immunohistochemistry and evaluated by a semi-quantification assay. Statistical analyses explored the relationship of YKL-40 with clinical outcome and other breast cancer biomarkers. RESULTS: Breast ductal carcinoma in situ expressed low and moderate levels of YKL-40. In the subset of 203 patients with invasive cancer, YKL-40 levels were positively correlated with tumour grade (P<0.0001) and Her2/neu (P<0.01), but negatively correlated with oestrogen (P<0.0001) and progesterone receptor (P<0.0001). YKL-40 levels were inversely correlated with expressions of GATA3 (P=0.0137) and E-cadherin (P=0.0417). CONCLUSION: These data demonstrate that expression levels of YKL-40 are associated with tumour grade, poor differentiation, and other breast cancer markers, highlighting that tissue levels of YKL-40 serve as a valuable biomarker for breast cancer diagnosis and prognosis.

In tumors Salmonella migrate away from vasculature toward the transition zone and induce apoptosis.

Motile bacteria can overcome diffusion resistances that substantially reduce the efficacy of standard cancer therapies. Many reports have also recently described the ability of Salmonella to deliver therapeutic molecules to tumors. Despite this potential, little is known about the spatiotemporal dynamics of bacterial accumulation in solid tumors. Ultimately this timing will affect how these microbes are used therapeutically. To determine how bacteria localize, we intravenously injected Salmonella typhimurium into BALB/c mice with 4T1 mammary carcinoma and measured the average bacterial content as a function of time. Immunohistochemistry was used to measure the extent of apoptosis, the average distance of bacteria from tumor vasculature and the location of bacteria in four different regions: the core, transition, body and edge. Bacteria accumulation was also measured in pulmonary and hepatic metastases. The doubling time of bacterial colonies in tumors was measured to be 16.8 h, and colonization was determined to delay tumor growth by 48 h. From 12 and 48 h after injection, the average distance between bacterial colonies and functional vasculature significantly increased from 130 to 310 µm. After 48 h, bacteria migrated away from the tumor edge toward the central core and induced apoptosis. After 96 h, bacteria began to marginate to the tumor transition zone. All observed metastases contained Salmonella and the extent of bacterial colocalization with metastatic tissue was 44% compared with 0.5% with normal liver parenchyma. These results demonstrate that Salmonella can penetrate tumor tissue and can selectively target metastases, two critical characteristics of a targeted cancer therapeutic.

YKL-40, a secreted glycoprotein, promotes tumor angiogenesis.

Tumor angiogenesis is of paramount importance in solid tumor development. Elevated serum levels of YKL-40, which is a secreted heparin-binding glycoprotein, have been associated with a worse prognosis from various advanced human cancers. Yet the role of YKL-40 activity in these cancers is still missing. In this study, we showed that ectopic expression of YKL-40 in MDA-MB-231 breast cancer cells and in HCT-116 colon cancer cells led to larger tumor formation with an extensive angiogenic phenotype than did control cancer cells in mice. Affinity-purified recombinant YKL-40 protein promoted vascular endothelial cell angiogenesis in vitro, the effects of which are similar to the activities observed using MDA-MB-231 and HCT-116 cell-conditioned medium after transfection with YKL-40. Furthermore, YKL-40 was found to induce coordination of membrane-bound receptor syndecan-1 and integrin alpha(v)beta(3) and to activate an intracellular signaling cascade, including focal adhesion kinase and mitogen-activated protein kinase extracellular signal-related kinase1/2 in endothelial cells. Moreover, blockade of YKL-40 using small-interfering RNA gene knockdown suppressed tumor angiogenesis in vitro and in vivo. Immunohistochemical analysis of human breast cancer showed a correlation between YKL-40 expression and blood vessel density. These findings provide novel insights into angiogenic activities and molecular mechanisms of YKL-40 in cancer development.

Outer membrane protein (OMP) based vaccine for Neisseria meningitidis serogroup B.

A family of outer membrane lipoproteins of Neisseria meningitidis, LP2086, has been shown to induce serum bactericidal activity against a broad variety of meningococcal strains. Two sub-families of serologically distinct LP2086 proteins (A and B) have been identified. In the present study, we have shown that polyclonal anti-serum against rLP2086 is protective in vivo in an infant rat passive-protection model. Additionally, the LP2086 protein is displayed on the surface of 91% meningococcal strains as measured in a whole cell ELISA using polyclonal anti-sera raised against these proteins. We also demonstrate based on the reactivity of anti-rLP2086 antibody with recombinantly expressed C- and N-terminal fragments of rLP2086 in a Western blot assay that the C-terminal fragment of LP2086 dictates sub-family specificity and the N-terminal fragment determines the family specificity. A formulation containing family A and B of LP2086 potentially would provide broad protection against a majority of Neisseria meningitidis strains.

Prolonged inhibition of muscle carnitine palmitoyltransferase-1 promotes intramyocellular lipid accumulation and insulin resistance in rats.

Cross-sectional studies in human subjects have used 1H magnetic resonance spectroscopy (HMRS) to demonstrate that insulin resistance correlates more tightly with the intramyocellular lipid (IMCL) concentration than with any other identified risk factor. To further explore the interaction between these two elements in the rat, we used two strategies to promote the storage of lipids in skeletal muscle and then evaluated subsequent changes in insulin-mediated glucose disposal. Normal rats received either a low-fat or a high-fat diet (20% lard oil) for 4 weeks. Two additional groups (lowfat + etoxomir and lard + etoxomir) consumed diets containing 0.01% of the carnitine palmitoyltransferase-1 inhibitor, R-etomoxir, which produced chronic blockade of enzyme activity in liver and skeletal muscle. Both the high-fat diet and drug treatment significantly impaired insulin sensitivity, as measured with the hyperinsulinemic-euglycemic clamp. Insulin-mediated glucose disposal (IMGD) fell from 12.57 +/- 0.72 in the low-fat group to 9.79 +/- 0.59, 8.96 +/- 0.38, and 7.32 +/- 0.28 micromol x min(-1) x 100 g(-1) in the low-fat + etoxomir, lard, and lard + etoxomir groups, respectively. We used HMRS, which distinguishes between fat within the myocytes and fat associated with contaminating adipocytes located in the muscle bed, to assess the IMCL content of isolated soleus muscle. A tight inverse relationship was found between IMGD and IMCL, the correlation (R = 0.96) being much stronger than that seen between IMGD and either fat mass or weight. In conclusion, either a diet rich in saturated fat or prolonged inhibition of fatty acid oxidation impairs IMGD in rats via a mechanism related to the accumulation of IMCL.

Visceral organ mass and cellularity in growth-restricted and refed beef steers.

Beef steers were fed in two phases to compare the effects of diet and intake on growth and cellularity of visceral organs. During the growing phase (237 to 327 kg), steers were fed either a high (C) or low (F) concentrate diet. Diet F was available ad libitum (FA), whereas diet C was available either ad libitum (CA) or on a limited basis (CL) to match live weight gains of the FA group. During the finishing phase (327 to 481 kg), all steers received diet C either ad libitum (CA-CA, CL-CA, and FA-CA) or restricted (CL-CL and FA-CL) to 70% of the intakes of corresponding CA steers. Marked nutritional effects on liver growth (e.g., -25 and -15% in CL and FA, respectively, relative to CA) were due mainly to changes in cell size (i.e., protein:DNA), with smaller changes in cell numbers (i.e., DNA). Hyperplasia and hypertrophy played a role in growth of the forestomachs, although cell numbers and sizes tended to change in opposite directions, limiting magnitudes of changes in organ mass. Protein synthetic capacity (i.e., RNA) varied as well, often in parallel with cell number. This result differed from that observed in intestines, which maintained constant cell sizes but underwent marked changes in cell number. For liver, amounts of absorbed nutrients seemed to be the main factor driving hypertrophy. The organs of the gastrointestinal tract responded to physical and chemical signals, as shown by the effects of dietary fiber on growth of the forestomachs and intestines. Forestomachs responded mainly to diet fiber content, whereas the intestines responded to diet type and nutrient supply. Feeding programs for beef animals often include changes in diet type and periods of feed limitation, and these in turn affect visceral organ growth and metabolism. Because visceral organs are a major contributor to whole-body energy expenditures, factors affecting these tissues must be understood. This study supports the concept that workload determines organ size, but dietary factors influencing workload clearly vary for each organ.

Removal of minute foreign bodies.

The precise localization and surgical removal of the broken tip of an acupuncture needle is reported. The needle was suspected of causing chronic suppuration and sinus formation in the patient's leg. A localizing guide-wire was inserted pre-operatively under fluoroscopic control. Subsequent surgical removal of the foreign body was carried out swiftly and simply with the aid of an image intensifier.

Airway management practices in emergency medicine residencies.

The Core Content for Emergency Medicine (EM) recommends that all emergency physicians be trained to manage the airway, including administering paralytic agents for endotracheal intubation. This study analyzed compliance with the recommendations by reviewing airway management practices at EM residencies. All 96 EM residency directors were sent a 10-item survey characterizing airway management practices at residency-affiliated emergency departments (EDs). The 91 respondents (95%) represented residencies with 120 affiliated hospitals. Paralytic agents routinely were used during intubations in 114 of the EDs (95%). Forty-nine of the Eds (41%) never requested an anesthesiologist for intubations, and 8 Eds (7%) mandated anesthesiology presence during paralytic agent administration. The Department of Anesthesiology never performed quality assurance (QA) evaluations in at least 64 EDs (53%). The Department of Emergency Medicine performed QA checks less than two thirds of the time in at least 44 EDs (36%). The majority of EM residencies are complying with the Core Content recommendations by actively performing intubations using paralytic agents. Anesthesiologists are infrequently consulted in residency-affiliated EDs. Quality assurance of ED intubations is not rigorously monitored by emergency and anesthesiology departments.

Survey of follow-up systems in emergency medicine residencies: analysis and proposal.

OBJECTIVE: For educational purposes, the Residency Review Committee for Emergency Medicine requires that emergency medicine residencies "provide a mechanism for each resident to obtain information on outcomes of patients the resident has evaluated in the emergency department." The authors analyzed the current patient follow-up systems of emergency medicine residencies and, based upon survey results propose a comprehensive organized system of follow-up. METHODS: The 84 emergency medicine residency directors listed in the 1991 Society for Academic Emergency Medicine Handbook were polled regarding the current follow- up systems at all hospitals affiliated with their residencies. The survey contained 11 items, including two five-point Likert scales for rating system effectiveness and satisfaction. A description of each hospital's follow-up system was requested, and other comments were reviewed. RESULTS: The 72 (86%) respondents represented residencies with a total of 138 affiliated hospitals, of which 89 (64.5%) had formal follow-up systems. Of those 89 hospitals, 39% (n = 80) residency directors reported that fewer than half of their residents used the systems, 63% (n = 87) had mandatory compliance policies; 53% had the capability for residents to obtain discharge summaries on admitted patients; and 66% (n = 83) had mechanisms for follow-up of patients released from the emergency department. Twenty-three percent of the systems were considered effective, with ratings of 4 or higher and only 31% received satisfaction ratings of 4 or more. CONCLUSIONS: Most emergency residency-affiliated hospitals in our survey had follow-up systems in place. Of existing systems, only a minority were rated by residency directors as effective or satisfactory. A model for a comprehensive system of patient follow-up is proposed.

Cystic fibrosis in the United Kingdom, 1968-1988: incidence, population and survival.

A thorough survey was conducted of patients with cystic fibrosis living in the UK from 1977 onwards. This was supplemented with death certificate data back to 1968. There was one case identified for each 2475 births. The total number of cases in the UK rose linearly from 4086 in 1977 to 5426 in 1988 and is estimated to be 6000 in 1992. The probability of survival improved in the period under study for all age groups and in both sexes. It was worst in the first year of life, dropped sharply thereafter but then increased steadily with age. There has been a very marked improvement over the years in survival in the first year of life, but a lesser one in older age groups. Male mortality was greater than that in females in the first year of life, but less in subsequent years giving, overall, worse survival for females. A set of cohort and 'current' survival graphs for the two sexes are given.

Cold-induced urticaria and angioedema: diagnosis and management.

The physical urticarias compromise a heterogeneous group of disorders characterized by their propensity to form urticarial lesions after exposure to certain physical stimuli, such as heat, vibration, or cold. Although generally benign, systemic hypotension and angioedematous airway compromise are known life-threatening complications. We present the case of a man who experienced benign angioedematous changes in response to cold exposure, and discuss the clinical course, diagnosis, and management of cold urticaria.

Synchronous eruption of cotton-induced granulomas 45 years after exposure: report of an unusual case.

A 58-year-old woman developed multiple, recurrent abscesses and subcutaneous nodules over both buttocks during a 12-year period. Microbiological studies of surgical biopsy specimens were inconclusive for a specific infectious cause, but histochemical preparations on several separate occasions revealed an exuberant foreign body reaction to raw cotton fibers. Interestingly, the patient gave a detailed history of sliding down piles of cotton hulls during her childhood, some 45 years earlier. With a probable cause-and-effect relationship established, we postulate a dramatically delayed foreign body granulomatous reaction to cotton fibers.