My advice to my kids and anyone who'll listen is this: do not buy a new apartment, especially if it is over three storeys high, writes Philip Gall.

I mentioned a couple weeks ago that it’s always a good idea to pick colors you enjoy embroidering with. If …

An idea has been bubbling around in my brain for a while. And since this past weekend was a perfect …

Oh golly. I really wanted to show off some serious stitching today. But in fact, I ran into one of …

You can iron your embroidery. I do it all the time! But I hear from a lot of people who …

Personally, I don’t enjoy stitching two similar embroidery projects simultaneously. Sometimes I do this, so that I can troubleshoot or …

By Wadner Pierre

This article was originally published by UnlessWeCare.org

Screen Shot 2015-11-06 at 6.34.24 AM It has been over a month since Haiti’s Conseil Electoral Provisoire (Electoral Provisory Counsel), known as CEP, published its foreknown controversial fraudulent results for the first round presidential and second round legislative elections. The CEP’s preliminary results for the presidential elections placed President Michel Martelly’s hand-picked candidate Jovenel Moise of Parti Haïtien Tèt Kale, or P.H.T.K in the first place with 32.8 percent of the popular votes. Jaccéus Joseph, a member of the electoral council, qualified the results as unacceptable.

Miami Herald’s Jacqueline Charles reported, Joseph refused to sign “the presidential and legislative preliminary results” because of irregularities and frauds that plagued them. Joseph thought his refusal to endorse the results would prompt the Tabulation Center to verify “the allegations of electoral fraud, including checking the voter registration lists against the ballots cast in the Oct. 25” elections to avert an unnecessary electoral crisis.

Joseph said, “We asked the director of the Tabulation Center did he have enough time to thoroughly verify if there was fraud.” According to Joseph, the director told them, “[H]e didn’t have enough time for that.”

Despite Joseph’s insistence on verifying and correcting the irregularities and frauds threatening the credibility of the results, CEP’s President Pierre-Louis Opont decided to publish the tainted results. The electoral crisis that was avoidable is now becoming an inevitable crisis. This man-made electoral dispute could further derail the political and social stability of the country.

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Embroidery.

Paris : V.A. Delahaye, 1877.

Clostridioides difficile, the leading cause of nosocomial infections, is an urgent health threat worldwide. The increased incidence and severity of disease, the high recurrence rates, and the dearth of effective anticlostridial drugs have created an urgent need for new therapeutic agents. In an effort to discover new drugs for treatment of Clostridioides difficile infections (CDIs), we investigated a panel of FDA-approved antiparasitic drugs against C. difficile and identified diiodohydroxyquinoline (DIHQ), an FDA-approved oral antiamoebic drug. DIHQ exhibited potent activity against 39 C. difficile isolates, inhibiting growth of 50% and 90% of these isolates at the concentrations of 0.5 μg/mL and 2 μg/mL, respectively. In a time-kill assay, DIHQ was superior to vancomycin and metronidazole, reducing a high bacterial inoculum by 3-log₁₀ within six hours. Furthermore, DIHQ reacted synergistically with vancomycin and metronidazole against C. difficile in vitro. Moreover, at subinhibitory concentrations, DIHQ was superior to vancomycin and metronidazole in inhibiting two key virulence factors of C. difficile, toxin production and spore formation. Additionally, DIHQ did not inhibit growth of key species that compose the host intestinal microbiota, such as Bacteroides, Bifidobacterium and Lactobacillus spp. Collectively, our results indicate that DIHQ is a promising anticlostridial drug that warrants further investigation as a new therapeutic for CDIs.

"Big love with my little love," wrote Mira

ABSTRACT

Frequent and excessive use of antibiotics primes patients to Clostridioides difficile infection (CDI), which leads to fatal pseudomembranous colitis, with limited treatment options. In earlier reports, we used a drug repurposing strategy and identified amoxapine (an antidepressant), doxapram (a breathing stimulant), and trifluoperazine (an antipsychotic), which provided significant protection to mice against lethal infections with several pathogens, including C. difficile. However, the mechanisms of action of these drugs were not known. Here, we provide evidence that all three drugs offered protection against experimental CDI by reducing bacterial burden and toxin levels, although the drugs were neither bacteriostatic nor bactericidal in nature and had minimal impact on the composition of the microbiota. Drug-mediated protection was dependent on the presence of the microbiota, implicating its role in evoking host defenses that promoted protective immunity. By utilizing transcriptome sequencing (RNA-seq), we identified that each drug increased expression of several innate immune response-related genes, including those involved in the recruitment of neutrophils, the production of interleukin 33 (IL-33), and the IL-22 signaling pathway. The RNA-seq data on selected genes were confirmed by quantitative real-time PCR (qRT-PCR) and protein assays. Focusing on amoxapine, which had the best anti-CDI outcome, we demonstrated that neutralization of IL-33 or depletion of neutrophils resulted in loss of drug efficacy. Overall, our lead drugs promote disease alleviation and survival in the murine model through activation of IL-33 and by clearing the pathogen through host defense mechanisms that critically include an early influx of neutrophils.

IMPORTANCE Clostridioides difficile is a spore-forming anaerobic bacterium and the leading cause of antibiotic-associated colitis. With few therapeutic options and high rates of disease recurrence, the need to develop new treatment options is urgent. Prior studies utilizing a repurposing approach identified three nonantibiotic Food and Drug Administration-approved drugs, amoxapine, doxapram, and trifluoperazine, with efficacy against a broad range of human pathogens; however, the protective mechanisms remained unknown. Here, we identified mechanisms leading to drug efficacy in a murine model of lethal C. difficile infection (CDI), advancing our understanding of the role of these drugs in infectious disease pathogenesis that center on host immune responses to C. difficile. Overall, these studies highlight the crucial involvement of innate immune responses, as well as the importance of immunomodulation as a potential therapeutic option to combat CDI.

ABSTRACT

Clostridioides difficile is an important nosocomial pathogen that causes approximately 500,000 cases of C. difficile infection (CDI) and 29,000 deaths annually in the United States. Antibiotic use is a major risk factor for CDI because broad-spectrum antimicrobials disrupt the indigenous gut microbiota, decreasing colonization resistance against C. difficile. Vancomycin is the standard of care for the treatment of CDI, likely contributing to the high recurrence rates due to the continued disruption of the gut microbiota. Thus, there is an urgent need for the development of novel therapeutics that can prevent and treat CDI and precisely target the pathogen without disrupting the gut microbiota. Here, we show that the endogenous type I-B CRISPR-Cas system in C. difficile can be repurposed as an antimicrobial agent by the expression of a self-targeting CRISPR that redirects endogenous CRISPR-Cas3 activity against the bacterial chromosome. We demonstrate that a recombinant bacteriophage expressing bacterial genome-targeting CRISPR RNAs is significantly more effective than its wild-type parent bacteriophage at killing C. difficile both in vitro and in a mouse model of CDI. We also report that conversion of the phage from temperate to obligately lytic is feasible and contributes to the therapeutic suitability of intrinsic C. difficile phages, despite the specific challenges encountered in the disease phenotypes of phage-treated animals. Our findings suggest that phage-delivered programmable CRISPR therapeutics have the potential to leverage the specificity and apparent safety of phage therapies and improve their potency and reliability for eradicating specific bacterial species within complex communities, offering a novel mechanism to treat pathogenic and/or multidrug-resistant organisms.

IMPORTANCE Clostridioides difficile is a bacterial pathogen responsible for significant morbidity and mortality across the globe. Current therapies based on broad-spectrum antibiotics have some clinical success, but approximately 30% of patients have relapses, presumably due to the continued perturbation to the gut microbiota. Here, we show that phages can be engineered with type I CRISPR-Cas systems and modified to reduce lysogeny and to enable the specific and efficient targeting and killing of C. difficile in vitro and in vivo. Additional genetic engineering to disrupt phage modulation of toxin expression by lysogeny or other mechanisms would be required to advance a CRISPR-enhanced phage antimicrobial for C. difficile toward clinical application. These findings provide evidence into how phage can be combined with CRISPR-based targeting to develop novel therapies and modulate microbiomes associated with health and disease.

ABSTRACT

The human gut microbiota (HGM) has far-reaching impacts on human health and nutrition, which are fueled primarily by the metabolism of otherwise indigestible complex carbohydrates commonly known as dietary fiber. However, the molecular basis of the ability of individual taxa of the HGM to address specific dietary glycan structures remains largely unclear. In particular, the utilization of β(1,3)-glucans, which are widespread in the human diet as yeast, seaweed, and plant cell walls, had not previously been resolved. Through a systems-based approach, here we show that the symbiont Bacteroides uniformis deploys a single, exemplar polysaccharide utilization locus (PUL) to access yeast β(1,3)-glucan, brown seaweed β(1,3)-glucan (laminarin), and cereal mixed-linkage β(1,3)/β(1,4)-glucan. Combined biochemical, enzymatic, and structural analysis of PUL-encoded glycoside hydrolases (GHs) and surface glycan-binding proteins (SGBPs) illuminates a concerted molecular system by which B. uniformis recognizes and saccharifies these distinct β-glucans. Strikingly, the functional characterization of homologous β(1,3)-glucan utilization loci (1,3GUL) in other Bacteroides further demonstrated that the ability of individual taxa to utilize β(1,3)-glucan variants and/or β(1,3)/β(1,4)-glucans arises combinatorially from the individual specificities of SGBPs and GHs at the cell surface, which feed corresponding signals to periplasmic hybrid two-component sensors (HTCSs) via TonB-dependent transporters (TBDTs). These data reveal the importance of cooperativity in the adaptive evolution of GH and SGBP cohorts to address individual polysaccharide structures. We anticipate that this fine-grained knowledge of PUL function will inform metabolic network analysis and proactive manipulation of the HGM. Indeed, a survey of 2,441 public human metagenomes revealed the international, yet individual-specific, distribution of each 1,3GUL.

IMPORTANCE Bacteroidetes are a dominant phylum of the human gut microbiota (HGM) that target otherwise indigestible dietary fiber with an arsenal of polysaccharide utilization loci (PULs), each of which is dedicated to the utilization of a specific complex carbohydrate. Here, we provide novel insight into this paradigm through functional characterization of homologous PULs from three autochthonous Bacteroides species, which target the family of dietary β(1,3)-glucans. Through detailed biochemical and protein structural analysis, we observed an unexpected diversity in the substrate specificity of PUL glycosidases and glycan-binding proteins with regard to β(1,3)-glucan linkage and branching patterns. In combination, these individual enzyme and protein specificities support taxon-specific growth on individual β(1,3)-glucans. This detailed metabolic insight, together with a comprehensive survey of individual 1,3GULs across human populations, further expands the fundamental roadmap of the HGM, with potential application to the future development of microbial intervention therapies.

ABSTRACT

Insights into the interaction between phages and their bacterial hosts are crucial for the development of phage therapy. However, only one study has investigated global gene expression of Clostridioides (formerly Clostridium) difficile carrying prophage, and transcriptional reprogramming during lytic infection has not been studied. Here, we presented the isolation, propagation, and characterization of a newly discovered 35,109-bp phage, JD032, and investigated the global transcriptomes of both JD032 and C. difficile ribotype 078 (RT078) strain TW11 during JD032 infection. Transcriptome sequencing (RNA-seq) revealed the progressive replacement of bacterial host mRNA with phage transcripts. The expressed genes of JD032 were clustered into early, middle, and late temporal categories that were functionally similar. Specifically, a gene (JD032_orf016) involved in the lysis-lysogeny decision was identified as an early expression gene. Only 17.7% (668/3,781) of the host genes were differentially expressed, and more genes were downregulated than upregulated. The expression of genes involved in host macromolecular synthesis (DNA/RNA/proteins) was altered by JD032 at the level of transcription. In particular, the expression of the ropA operon was downregulated. Most noteworthy is that the gene expression of some antiphage systems, including CRISPR-Cas, restriction-modification, and toxin-antitoxin systems, was suppressed by JD032 during infection. In addition, bacterial sporulation, adhesion, and virulence factor genes were significantly downregulated. This study provides the first description of the interaction between anaerobic spore-forming bacteria and phages during lytic infection and highlights new aspects of C. difficile phage-host interactions.

IMPORTANCE C. difficile is one of the most clinically significant intestinal pathogens. Although phages have been shown to effectively control C. difficile infection, the host responses to phage predation have not been fully studied. In this study, we reported the isolation and characterization of a new phage, JD032, and analyzed the global transcriptomic changes in the hypervirulent RT078 C. difficile strain, TW11, during phage JD032 infection. We found that bacterial host mRNA was progressively replaced with phage transcripts, three temporal categories of JD032 gene expression, the extensive interplay between phage-bacterium, antiphage-like responses of the host and phage evasion, and decreased expression of sporulation- and virulence-related genes of the host after phage infection. These findings confirmed the complexity of interactions between C. difficile and phages and suggest that phages undergoing a lytic cycle may also cause different phenotypes in hosts, similar to prophages, which may inspire phage therapy for the control of C. difficile.

Clostridioides difficile infection (CDI) is one of the most common health care-associated infections that can cause significant morbidity and mortality. CDI diagnosis involves laboratory testing in conjunction with clinical assessment. The objective of this study was to assess the performance of various C. difficile tests and to compare clinical characteristics, Xpert C. difficile/Epi (PCR) cycle threshold (C_T), and Singulex Clarity C. diff toxins A/B (Clarity) concentrations between groups with discordant test results. Unformed stool specimens from 200 hospitalized adults (100 PCR positive and 100 negative) were tested by cell cytotoxicity neutralization assay (CCNA), C. diff Quik Chek Complete (Quik Chek), Premier Toxins A and B, and Clarity. Clinical data, including CDI severity and CDI risk factors, were compared between discordant test results. Compared to CCNA, PCR had the highest sensitivity at 100% and Quik Chek had the highest specificity at 100%. Among clinical and laboratory data studied, prevalences of leukocytosis, prior antibiotic use, and hospitalizations were consistently higher across all subgroups in comparisons of toxin-positive to toxin-negative patients. Among PCR-positive samples, the median C_T was lower in toxin-positive samples than in toxin-negative samples; however, C_T ranges overlapped. Among Clarity-positive samples, the quantitative toxin concentration was significantly higher in toxin-positive samples than in toxin-negative samples as determined by CCNA and Quik Chek Toxin A and B. Laboratory tests for CDI vary in sensitivity and specificity. The quantitative toxin concentration may offer value in guiding CDI diagnosis and treatment. The presence of leukocytosis, prior antibiotic use, and previous hospitalizations may assist with CDI diagnosis, while other clinical parameters may not be consistently reliable.

Clostridioides difficileDiagnosticsMetabolomicsMicrobiome

Pub visits should be avoided when social distancing measures are eased, one of the UK's top medics has said.

Pub visits should be avoided even after coronavirus restrictions are lifted, England's deputy chief medical officer has indicated.

Le commissaire a évoqué l’annulation de la saison.

In vitro and rat studies suggest inhibiting the enzymatic activity of house dust mite (HDM) allergens could help treat allergic asthma.

Most of us alive today owe a debt to those who avoided nuclear war in years past, and sadly, there were many occasions when that was necessary.

The trick is to get comfortable asking one question.

Winter is all about wearability and comfort, but don't make it an excuse to let go of the style quotient. Break away from conventional silhouettes and experiment with versatile trends like embroidered capes or structured peplums to beat the chill, say fashion gurus.Ace fashion designer Manish Malhotra, who has dressed up beauties likes Kajol, Karisma Kapoor, Kareena Kapoor Khan, Rani Mukerji, Aishwarya Rai Bachchan and Preity Zinta, feels one should stick to layering, but incorporate vintage hues. "Winter is all about comfort in style as we break away from conventional silhouettes and experiment with versatile trends that cater to a young global audience. As we mark the beginning of festivities in India, my latest collection spotlights layering as the key highlight of the season; I love layering as a trend and I always incorporate it even in my personal style," Malhotra told IANS.

"Crafted in vintage hues of chrome, ivory, oyster grey and rose, organza capes, trench jackets, and silken kimonos draped over tea-length dresses and layered skirts add an innovative twist to the young, glamourous women. For the modern gentleman, cowl-necked kurta-shirts with embroidered dinner jackets and velvet drapes help accentuate European accent to the classic ensemble," he added. Designer duo Ankur and Priyanka Modi, who established their brand AM:PM 15 years ago, believe in modern simplicity. "Winter is all about wearability, comfort and style and this season we break the monotony of traditional influences to introduce bold, power silhouettes as the versatile trend to adapt. Crafted in luxurious fabrics of velvet and silk, jackets, long or short, add an understated glamour to a classic silhouette," they shared a joint view with IANS.

Pointing out the trends to go for, they said: "Be it the embroidered capes or structured peplums, each garment can be effortlessly paired across any occasion and are thus, our staple must-have choice for the season." A lot of people associate winter with black and grey. But try hues like pomegranate red and aubergine, says Deepshikha Khanna, Head of Product Development (Apparel) for Sustain, Good Earth, India. "At Good Earth, our design philosophy revolves around translating simple everyday luxury for fashion lovers across the globe. With the festivities ushering in, our Sustain range highlights fusion wear as the emerging trend for the winter season," Deepshikha said. "Breezy kurtas worn with palazzos and printed scarves make an ideal choice for a casual day brunch while embroidered shararas and angrakhas crafted in deep, winter hues of pomegranate red, aubergine and charcoal is perfect for an evening outing. Indigenous fabrics of chanderi, silk, velvet and brocade flaunt versatility and comfort and can be styled effortlessly from day to night across various occasions."

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New Zealand reported five new Coronavirus cases Monday as the nation got ready to ease the rules on a strict lockdown from midnight. Prime Minister Jacinda Ardern said there hasn't been widespread community transmission of the virus and the country has so far managed to avoid the worst scenarios for an outbreak.

She said it would continue to hunt down the last few cases. From midnight, certain businesses such as construction will be allowed to reopen, but social distancing rules will still apply. Ardern said the nation was opening up the economy, but not people's social lives.

S Korea to reopen schools
South Korea reported only 10 new cases, its 26th straight day below 100 as officials mulled reopening schools amid the slowing caseload. The figures released by the Korea Centers for Disease Control and Prevention on Monday brought the national totals to 10,738 cases and 243 deaths.

At least 1,044 infections have been linked to international arrivals, but such cases have also declined in recent weeks amid tightened border controls.

Prime Minster Chung Sye-kyun during a virus meeting Monday instructed education officials to prepare measures to ensure hygiene and enforce distance between students at schools so the government could announce a timeline for reopening schools no later than early May.

More US states to reopen
In the US, Colorado, Mississippi, Minnesota, Montana and Tennessee are also preparing to reopen economy, Reuters reported. Georgia, Oklahoma, Alaska and South Carolina had already started easing restrictions. "I would stay home if the government encouraged that, but they're not. They're saying, 'Hey, the best thing to do is go back to work, even though it might be risky,'" Royal Rose, 39, owner of a tattoo studio in Greeley, Colorado, told Reuters.

According to reports, the states have started easing lockdown without ensuring measures to trace the asymptomatic cases. Several health experts have warned that a hurry in easing lockdown may lead to a fresh wave of infections. Meanwhile, the White House said the jobless rate would be 16 per cent or higher this month. A record 26.5 million Americans have filed for unemployment since mid-March.

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HIV outbreak among people who administer drugs in Indiana from 2011 to 2015 could have been prevented if the state's top health officials had responded sooner on warnings, reports a new study.

Exports of Embroideries in Switzerland decreased to 2.29 CHF Million in March from 2.99 CHF Million in February of 2020. Exports of Embroideries in Switzerland averaged 11.22 CHF Million from 1988 until 2020, reaching an all time high of 25.75 CHF Million in October of 1990 and a record low of 1.58 CHF Million in August of 2016. This page includes a chart with historical data for Switzerland Exports of Embroideries.

The pop icon, 61, wrapped up in a quirky black embroidered overcoat on Friday as she attempted to make a low-key arrival at the venue for her concert in New York at the weekend.

Rose McGowan tore into Natalie Portman in a scathing Facebook post, calling her fashion protest 'deeply offensive' and likening her to 'an actress acting the part of someone who cares.'

British literary expert Patricia Nichol, shares a selection of fascinating book son embroidery including The Testaments and A Single Thread.

The ten rock reliefs were unearthed in the Kurdistan region of Iraq just 15 miles away from ISIS at the height of its powers and are believed to be the first discovery of its kind in 150 years.

The twenty-year-old model and her sister Kourtney's ex didn't speak to each other at the bash, which was held at Hyde in West Hollywood on Tuesday. Instead, Scott hung out with French Montana.

Gwen Stefani was the epitome of chic on Saturday as she went shopping in a red jumpsuit and embroidered green jacket at The Grove in Los Angeles alongside her son Kingston.

The Oscar-winning star, 46, looked regal in a stunning black gown with sheer chiffon sleeves and a purple floral embroidered top.

Hannah Toohill, from Dingwall in Scotland, began experiencing crippling back and chest pain four months into her pregnancy before she was diagnosed with multiple myeloma.

Mira Rajput tries her hands at embroidery, takes daughter Misha Kapoor's help

Shahid and Mira Kapoor's daughter embroidered a pair of hearts on a cloth with the help of her mother which was proudly shared on Instagram.

Parasitoide Laboratory

Williams, Geoff, 1950- author, illustrator

Shahid Kapoor and Mira Rajput are reportedly self-quarantining in Punjab with their kids Misha and Zain. The duo has been making the most of their free time amid the lockdown and spending time with the family.

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For years Dior, Saint Laurent and other fashion brands have been quietly using Indian embroiderers, while offering little in the way of employment protection

The 2015 nuclear pact led to lifting of curbs and reconnection with the world