The diagnosis and treatment of elderly patients with acute exacerbation of chronic obstructive pulmonary disease and chronic bronchitis.

The syndrome of chronic obstructive pulmonary disease (COPD) consists of chronic bronchitis (CB), bronchiectasis, emphysema, and reversible airway disease that combine uniquely in an individual patient. Older patients are at risk for COPD and its components--emphysema, CB, and bronchiectasis. Bacterial and viral infections play a role in acute exacerbations of COPD (AECOPD) and in acute exacerbations of CB (AECB) without features of COPD. Older patients are at risk for resistant bacterial organisms during their episodes of AECOPD and AECB. Organisms include the more-common bacteria implicated in AECOPD/AECB such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Less-common nonenteric, gram-negative organisms including Pseudomonas aeruginosa, gram-positive organisms including Staphylococcus aureus, and strains of nontuberculosis Mycobacteria are more often seen in AECOPD/AECB episodes involving elderly patients with frequent episodes of CB or those with bronchiectasis. Risk-stratified antibiotic treatment guidelines appear useful for purulent episodes of AECOPD and episodes of AECB. These guidelines have not been prospectively validated for the general population and especially not for the elderly population. Using a risk-stratification approach for elderly patients, first-line antibiotics (e.g., amoxicillin, ampicillin, pivampicillin, trimethoprim/sulfamethoxazole, and doxycycline), with a more-limited spectrum of antibacterial coverage, are used in patients who are likely to have a low probability of resistant organisms during AECOPD/AECB. Second-line antibiotics (e.g., amoxicillin/clavulanic acid, second- or third-generation cephalosporins, and respiratory fluoroquinolones) with a broader spectrum of coverage are reserved for patients with significant risk factors for resistant organisms and those who have failed initial antibiotic treatment

SUSY Production From TeV Scale Blackhole at LHC

If the fundamental Planck scale is near a TeV, then we should expect to see TeV scale black holes at the LHC. Similarly, if the scale of supersymmetry breaking is sufficiently low, then we might expect to see light supersymmetric particles in the next generation of colliders. If the mass of the supersymmetric particle is of order a TeV and is comparable to the temperature of a typical TeV scale black hole, then such sparticles will be copiously produced via Hawking radiation: The black hole will act as a resonance for sparticles, among other things. In this paper we compared various signatures for SUSY production at LHC, and we contrasted the situation where the sparticles are produced directly via parton fusion processes with the situation where they are produced indirectly through black hole resonances. We found that black hole resonances provide a larger source for heavy mass SUSY (squark and gluino) production than the direct pQCD-SUSY production via parton fusion processes depending on the values of the Planck mass and blackhole mass. Hence black hole production at LHC may indirectly act as a dominant channel for SUSY production. We also found that the differential cross section d\sigma/dp_t for SUSY production increases as a function of the p_t (up to p_t equal to about 1 TeV or more) of the SUSY particles (squarks and gluinos), which is in sharp contrast with the pQCD predictions where the differential cross section d\sigma/dp_t decreases as p_t increases for high p_t about 1 TeV or higher. This is a feature for any particle emission from TeV scale blackhole as long as the temperature of the blackhole is very high (~ TeV). Hence measurement of increase of d\sigma/dp_t with p_t for p_t up to about 1 TeV or higher for final state particles might be a useful signature for blackhole production at LHC.Comment: Final Version, To Appear in Phys. Rev.

Expression and reconstitution of the bioluminescent Ca2+ reporter aequorin in human embryonic stem cells, and exploration of the presence of functional IP3 and ryanodine receptors during the early stages of their differentiation into cardiomyocytes

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Science China Life Sciences 59 (2016): 811-824, doi:10.1007/s11427-016-5094-6.In order to develop a novel method of visualizing possible Ca2+ signaling during the early differentiation of hESCs into cardiomyocytes and avoid some of the inherent problems associated with using fluorescent reporters, we expressed the bioluminescent Ca2+ reporter, apo-aequorin, in HES2 cells and then reconstituted active holo-aequorin by incubation with f-coelenterazine. The temporal nature of the Ca2+ signals generated by the holo-f-aequorin-expressing HES2 cells during the earliest stages of differentiation into cardiomyocytes was then investigated. Our data show that no endogenous Ca2+ transients (generated by release from intracellular stores) were detected in 1–12-day-old cardiospheres but transients were generated in cardiospheres following stimulation with KCl or CaCl2, indicating that holo-f-aequorin was functional in these cells. Furthermore, following the addition of exogenous ATP, an inositol trisphosphate receptor (IP3R) agonist, small Ca2+ transients were generated from day 1 onward. That ATP was inducing Ca2+ release from functional IP3Rs was demonstrated by treatment with 2-APB, a known IP3R antagonist. In contrast, following treatment with caffeine, a ryanodine receptor (RyR) agonist, a minimal Ca2+ response was observed at day 8 of differentiation only. Thus, our data indicate that unlike RyRs, IP3Rs are present and continually functional at these early stages of cardiomyocyte differentiation.This work was supported by the Hong Kong Theme-based Research Scheme award (T13-706/11-1), the Hong Kong Research Grants Council (RGC) General Research Fund awards (662113, 16101714, 16100115), the ANR/RGC joint research scheme award (A-HKUST601/13), and the Innovation and Technology Commission (ITCPD/17-9). HYSC was supported by a Hong Kong University Grants Council post-graduate studentship (T13-706/11- 11PG)

Metatranscriptome of human faecal microbial communities in a cohort of adult men

The gut microbiome is intimately related to human health, but it is not yet known which functional activities are driven by specific microorganisms\u27 ecological configurations or transcription. We report a large-scale investigation of 372 human faecal metatranscriptomes and 929 metagenomes from a subset of 308 men in the Health Professionals Follow-Up Study. We identified a metatranscriptomic \u27core\u27 universally transcribed over time and across participants, often by different microorganisms. In contrast to the housekeeping functions enriched in this core, a \u27variable\u27 metatranscriptome included specialized pathways that were differentially expressed both across participants and among microorganisms. Finally, longitudinal metagenomic profiles allowed ecological interaction network reconstruction, which remained stable over the six-month timespan, as did strain tracking within and between participants. These results provide an initial characterization of human faecal microbial ecology into core, subject-specific, microorganism-specific and temporally variable transcription, and they differentiate metagenomically versus metatranscriptomically informative aspects of the human faecal microbiome

Experimental manipulation of immune-mediated disease and its fitness costs for rodent malaria parasites

<p>Abstract</p> <p>Background</p> <p>Explaining parasite virulence (harm to the host) represents a major challenge for evolutionary and biomedical scientists alike. Most theoretical models of virulence evolution assume that virulence arises as a direct consequence of host exploitation, the process whereby parasites convert host resources into transmission opportunities. However, infection-induced disease can be immune-mediated (immunopathology). Little is known about how immunopathology affects parasite fitness, or how it will affect the evolution of parasite virulence. Here we studied the effects of immunopathology on infection-induced host mortality rate and lifetime transmission potential – key components of parasite fitness – using the rodent malaria model, <it>Plasmodium chabaudi chabaudi</it>.</p> <p>Results</p> <p>Neutralizing interleukin [IL]-10, an important regulator of inflammation, allowed us to experimentally increase the proportion of virulence due to immunopathology for eight parasite clones. <it>In vivo </it>blockade of the IL-10 receptor (IL-10R) with a neutralizing antibody resulted in a shorter time to death that was independent of parasite density and was particularly marked for normally avirulent clones. This suggests that IL-10 induction may provide a pathway to avirulence for <it>P. c. chabaudi</it>. Despite the increased investment in transmission-stage parasites observed for some clones in response to IL-10R blockade, experimental enhancement of immunopathology incurred a uniform fitness cost to all parasite clones by reducing lifetime transmission potential.</p> <p>Conclusion</p> <p>This is the first experimental study to demonstrate that infection-induced immunopathology and parasite genetic variability may together have the potential to shape virulence evolution. In accord with recent theory, the data show that some forms of immunopathology may select for parasites that make hosts less sick.</p

Versatile platform for nanotechnology based on circular permutations of chaperonin protein

The present invention provides chaperonin polypeptides which are modified to include N-terminal and C-terminal ends that are relocated from the central pore region to various different positions in the polypeptide which are located on the exterior of the folded modified chaperonin polypeptide. In the modified chaperonin polypeptide, the naturally-occurring N-terminal and C-terminal ends are joined together directly or with an intervening linker peptide sequence. The relocated N-terminal or C-terminal ends can be covalently joined to, or bound with another molecule such as a nucleic acid molecule, a lipid, a carbohydrate, a second polypeptide, or a nanoparticle. The modified chaperonin polypeptides can assemble into double-ringed chaperonin structures. Further, the chaperonin structures can organize into higher order structures such as nanofilaments or nanoarrays which can be used to produce nanodevices and nanocoatings

Long-term use of antibiotics and risk of colorectal adenoma

Objective—Recent evidence suggests that antibiotic use, which alters the gut microbiome, is associated with an increased risk of colorectal cancer. However, the association between antibiotic use and risk of colorectal adenoma, the precursor for the majority of colorectal cancers, has not been investigated. Design—We prospectively evaluated the association between antibiotic use at age 20–39 and 40–59 (assessed in 2004) and recent antibiotic use (assessed in 2008) with risk of subsequent colorectal adenoma among 16,642 women aged ≥60 enrolled in the Nurses’ Health Study who underwent at least one colonoscopy through 2010. We used multivariate logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results—We documented 1,195 cases of adenoma. Increasing duration of antibiotic use at age 20–39 (Ptrend=0.002) and 40–59 (Ptrend=0.001) was significantly associated with an increased risk of colorectal adenoma. Compared to non-users, women who used antibiotics for ≥2 months between age 20–39 had a multivariable OR of 1.36 (95% CI: 1.03–1.79). Women who used ≥2 months of antibiotics between age 40–59 had a multivariable OR of 1.69 (95% CI: 1.24–2.31). The associations were similar for low-risk vs. high-risk adenomas (size ≥1 cm, or with tubulovillous/villous histology, or ≥3 detected lesions), but appeared modestly stronger for proximal compared with distal adenomas. In contrast, recent antibiotic use within the past 4 years was not associated with risk of adenoma (Ptrend=0.44). Conclusions—Long-term antibiotic use in early to middle adulthood was associated with increased risk of colorectal adenoma

Rozpoznawanie i leczenie zaostrzeń przewlekłej obturacyjnej choroby płuc i przewlekłego zapalenia oskrzeli u chorych w podeszłym wieku

Na zespół przewlekłej obturacyjnej choroby płuc (POChP) składają się przewlekłe zapalenie oskrzeli (PZO), rozstrzenie oskrzeli, rozedma i odwracalne zmiany w drogach oddechowych, które tworzą swoiste połączenia u poszczególnych chorych. Chorzy w podeszłym wieku są narażeni na ryzyko zachorowania na POChP i jej składowe &#8212; rozedmę, PZO i rozstrzenie oskrzeli. Zakażenia bakteryjne i wirusowe odgrywają rolę w zaostrzeniach POChP i w zaostrzeniach PZO bez cech POChP. Chorzy w podeszłym wieku podczas epizodów zaostrzeń POChP i PZO są narażeni na ryzyko działania opornych bakterii, do których należą często stwierdzane w zaostrzeniach POChP i PZO między innymi Haemophilus influenzae, Moraxella catarrhalis i Streptococcus pneumoniae. Rzadziej spotykane niejelitowe bakterie Gram-ujemne, w tym Pseudomonas aeruginosa, bakterie Gram-dodatnie, w tym Staphylococcus aureus, i szczepy niegruźliczych mykobakterii są częściej stwierdzane w zaostrzeniach POChP/PZO u chorych w podeszłym wieku z częstymi epizodami PZO lub u pacjentów z rozstrzeniami oskrzeli. Wytyczne dotyczące leczenia antybiotykami w zależności od stopnia ryzyka wydają się użyteczne w przypadku ropnych zaostrzeń POChP i w zaostrzeniach PZO. Wytyczne te nie zostały prospektywnie potwierdzone dla ogólnej populacji ani w odniesieniu do grupy osób w podeszłym wieku. Posługując się stratyfikacją ryzyka dla chorych w podeszłym wieku, antybiotyki pierwszego rzutu (np. amoksycylina, ampicylina, piwampicylina, trimetoprim/sulfametoksazol i doksycyklina) z bardziej ograniczonym spektrum antybakteryjnym stosuje się u chorych, u których prawdopodobieństwo stwierdzenia w czasie zaostrzeń POChP/PZO opornych bakterii jest mniejsze. Antybiotyki drugiego rzutu (np. amoksycylina/ /kwas klawulanowy, cefalosporyny II lub III generacji i fluorochinolony stosowane w zakażeniach układu oddechowego) o szerszym spektrum działania są zarezerwowane dla chorych z istotnymi czynnikami ryzyka zakażenia opornymi drobnoustrojami i tych pacjentów, u których początkowe leczenie antybiotykami się nie powiodło. Medycyna Wieku Podeszłego 2011, 1 (1), 1&#8211;1

Language models show human-like content effects on reasoning

Abstract reasoning is a key ability for an intelligent system. Large language models achieve above-chance performance on abstract reasoning tasks, but exhibit many imperfections. However, human abstract reasoning is also imperfect, and depends on our knowledge and beliefs about the content of the reasoning problem. For example, humans reason much more reliably about logical rules that are grounded in everyday situations than arbitrary rules about abstract attributes. The training experiences of language models similarly endow them with prior expectations that reflect human knowledge and beliefs. We therefore hypothesized that language models would show human-like content effects on abstract reasoning problems. We explored this hypothesis across three logical reasoning tasks: natural language inference, judging the logical validity of syllogisms, and the Wason selection task (Wason, 1968). We find that state of the art large language models (with 7 or 70 billion parameters; Hoffman et al., 2022) reflect many of the same patterns observed in humans across these tasks -- like humans, models reason more effectively about believable situations than unrealistic or abstract ones. Our findings have implications for understanding both these cognitive effects, and the factors that contribute to language model performance