Antibiotic resistance: challenges and successes in respiratory infection.

European Respiratory Society Congress, Amsterdam, 26-30 September 2015, and CHEST 2015, Montréal, Canada, 24-28 October 2015 With approximately 50,000 deaths in the US and EU attributed to antibacterial resistance each year, together with several million days of hospital care [1], the need to address resistance mechanisms and find new targets for novel antibiotics has never been greater. At the annual congresses of the European Respiratory Society and the American College of Chest Physicians, presenters reported advances in understanding of the mechanisms of antibiotic resistance and how these may be overcome. The latest clinical trial data on antibiotic treatment for hospital- and community-acquired pneumonia, including the potential for novel nebulized forms of therapy, were also discussed.

Complete penoscrotal transposition: case report and review of the literature.

Penoscrotal transposition is a rare congenital abnormality. We report a case presenting prenatally with ambiguous genitalia and renal anomaly on obstetric ultrasound and fetal MRI and discuss the postnatal examination and autopsy findings. We present a review of the literature, including associated gene abnormalities.

Global antimicrobial resistance: from surveillance to stewardship. Part 1: surveillance and risk factors for resistance.

22nd European Congress of Clinical Microbiology and Infectious Diseases. London, UK, 31 March-3 April 2012. As concerns about global antibiotic resistance shift from Gram-positive to Gram-negative bacteria, the annual congress of the European Society of Clinical Microbiology and Infectious Diseases, in London (UK) provided a valuable opportunity for the nearly 10,000 delegates to discuss the latest global trends. In this first report from the conference, the authors review data from the SMART trial, which recently marked a decade of monitoring antibiotic resistance of Gram-negative bacteria from intra-abdominal infections, and from the rapidly developing European Antimicrobial Resistance Surveillance Network. The authors also focus on the spread of nonmetallo-ß-lactamase carbapenemases, and likely risk factors for resistance.

Global antimicrobial resistance: from surveillance to stewardship. Part 2: stewardship initiatives.

22nd European Congress of Clinical Microbiology and Infectious Diseases London, UK, 31 March-3 April 2012 Twelve months after the WHO launched its World Health Day 2011 campaign to combat antimicrobial resistance, antibiotic stewardship initiatives were a major focus at the annual meeting of the European Society of Clinical Microbiology and Infectious Diseases, in London, UK. In the second part of their report from the Congress, the authors review the impact of some of these initiatives in achieving their goals of reducing overall antibiotic usage, ensuring timely, appropriate prescribing and avoiding sub-optimal dosing and unnecessarily prolonged treatment. The authors also report new data on antibiotic prescribing in primary care and latest research in the development of novel antibiotics for the future.

Latest trends in fungal epidemiology inform treatment choices and stewardship initiatives.

Twelve months after the WHO launched its global campaign to safeguard current antimicrobial medicines for future generations, antifungal stewardship initiatives were a major focus for the 2012 European Congress of Clinical Microbiology and Infectious Diseases, in London, UK. Speakers from Europe, North and South America and Asia reported significant variations in fungal epidemiology and resistance, and demonstrated the value of multidisciplinary infectious disease advisory teams in monitoring local trends and making recommendations about the most appropriate antifungal treatment.

Developments in antimicrobial resistance and treatment.

On World Health Day (7 April 2011), the WHO urged rapid and concerted action to safeguard today's antimicrobial drug treatments against resistance, and published a package of policies for governments and their national partners to combat the growing threat. So the timing could not have been better for leading scientists and researchers to discuss the latest developments in antimicrobial resistance and treatment at this year's International Symposium on Antimicrobial Agents and Resistance, held in a region of the world - Asia-Pacific - that is facing some of the greatest challenges from extended-spectrum ß-lactamase-producing bacteria.

Managing invasive fungal disease in immunocompromised patients.

Celebrating its 30th anniversary in Budapest this year, the International Immunocompromised Host Society (ICHS) was established to advance the understanding of interactions between host defenses and microbial agents in order to improve the prevention and management of human disease in patients with compromised immune function. Much has been achieved in the intervening years, and presentations on the challenges of invasive fungal disease at this year's ICHS congress reflected the changing nature of the population at risk of fungal disease, the growing range of fungal pathogens, and evolving approaches to the prevention, diagnosis and treatment of fungal infection.

Managing invasive fungal infection in hematopoietic stem-cell transplantation.

Reduced intensity conditioning regimens and a wider range of donor sources, including cord blood, mean that more patients can be offered potentially curative allogeneic hematopoietic stem cell transplantation than ever before. Although these modalities aim to reduce procedure-related morbidity and mortality, their potential benefit may be overshadowed by a changing spectrum of problems related to the immunocompromised status of affected patients. Acute or chronic extensive graft-versus-host disease, which occasionally emerges in the late post-transplant period, and prolonged neutropenia due to delayed engraftment still carry a substantial risk of invasive fungal and other infections. As a result, advances in antifungal prophylaxis and pre-emptive treatment were widely reported at the 36th Annual Meeting of the European Group for Blood and Marrow Transplantation attended this year by approximately 3800 delegates.

Extreme variant of enlarged heterochromatin region on chromosome 9Q in a normal child and multiple family members.

Heteromorphisms of chromosome 9 are among the most common variations in the human karyotype. The pericentromeric polymorphisms of chromosome 9 include variations in the size of q-arm heterochromatin, pericentric inversions, and rarely, additional C-band-negative, G-band-positive material. The finding of a polymorphic variant, either in prenatal screening or in chromosomal analysis for phenotypic abnormalities, may cause parental anxiety and initiate genetic counselling. We report a case of a 39-year-old primigravida with unremarkable pregnancy, who had amniocentesis due to advanced maternal age. Chromosomal analysis demonstrated a long arm (q) variant of chromosome 9 with an enlarged heteromorphic area, approximately three times longer than known reported variants. Prenatal analysis demonstated an identical variant in the probands phenotypically normal father, uncle, and paternal grandmother, confirming an apparently "normal" variant.

Report from the European Congress of Clinical Microbiology and Infectious Diseases.

With its cool climate, Finland has a lower prevalence of fungal infections than many other European countries that have hosted the annual congress of the European Society of Clinical Microbiology and Infectious Diseases. However, changing patterns of infection and drug resistance, and their impact on treatment decisions, are as important to Nordic infectious disease specialists as to their colleagues in warmer countries. Similarly, developments in diagnostic techniques that enable fungal invasion to be identified before there is clinical evidence of infection will be a major step forward for physicians wherever they practise. It should therefore come as no surprise that this year's European Congress of Clinical Microbiology and Infectious Diseases was as well attended as previous meetings, with over 8000 participants arriving from all parts of Europe.

Mechanically stable porous cellulose media for affinity purification of family 9 cellulose-binding module-tagged fusion proteins.

A mechanically stable cellulose-based chromatography media was synthesized to permit inexpensive affinity purification of recombinant proteins containing the family 9 carbohydrate-binding module (CBM9) fused to either the N- or C-terminus of the target protein. A second-order response surface model was used to identify optimal concentrations of the primary reactants, epichlorohydrin and dimethyl sulfoxide (DMSO), required to cross-link the starting material, Perloza MT100, a compressible but inexpensive cellulose-based chromatography resin. This resulted in a mechanically stable cross-linked affinity chromatography media capable of operating at an order-of-magnitude higher linear velocity than permitted by unmodified MT100. Moments and Van Deemter analyses were used to show that rates of solute mass transfer within the column are largely unaffected by the cross-linking reaction, while the binding capacity decreased by 20% to 7.1 micromol of protein/g resin, a value superior to most commercial affinity chromatography media. In sharp contrast to MT100, the mechanical stability and purification performance of the cross-linked media are not diminished by scale-up or repeated column use.

New boundaries for lymphatic mapping-report of the Fifth International Sentinel Node Conference.

The Fifth Biennial International Sentinel Node Society meeting was held in Rome from 1 to 4 November 2006. Compared with previous meetings, there was a shift in focus from aspects of the clinical technique of the procedure to aspects of basic science that indicate the biology of the disease. The authors report on conference presentations relating to melanoma, including discussion of results from the Multicentre Selective Lymphadenectomy Trial 1 in intermediate thickness primary melanoma.

Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37.

The sole human cathelicidin peptide, LL-37, has been demonstrated to protect animals against endotoxemia/sepsis. Low, physiological concentrations of LL-37 (< or =1 microg/ml) were able to modulate inflammatory responses by inhibiting the release of the proinflammatory cytokine TNF-alpha in LPS-stimulated human monocytic cells. Microarray studies established a temporal transcriptional profile and identified differentially expressed genes in LPS-stimulated monocytes in the presence or absence of LL-37. LL-37 significantly inhibited the expression of specific proinflammatory genes up-regulated by NF-kappaB in the presence of LPS, including NFkappaB1 (p105/p50) and TNF-alpha-induced protein 2 (TNFAIP2). In contrast, LL-37 did not significantly inhibit LPS-induced genes that antagonize inflammation, such as TNF-alpha-induced protein 3 (TNFAIP3) and the NF-kappaB inhibitor, NFkappaBIA, or certain chemokine genes that are classically considered proinflammatory. Nuclear translocation, in LPS-treated cells, of the NF-kappaB subunits p50 and p65 was reduced > or =50% in the presence of LL-37, demonstrating that the peptide altered gene expression in part by acting directly on the TLR-to-NF-kappaB pathway. LL-37 almost completely prevented the release of TNF-alpha and other cytokines by human PBMC following stimulation with LPS and other TLR2/4 and TLR9 agonists, but not with cytokines TNF-alpha or IL-1beta. Biochemical and inhibitor studies were consistent with a model whereby LL-37 modulated the inflammatory response to LPS/endotoxin and other agonists of TLR by a complex mechanism involving multiple points of intervention. We propose that the natural human host defense peptide LL-37 plays roles in the delicate balancing of inflammatory responses in homeostasis as well as in combating sepsis induced by certain TLR agonists.

Implementing NICE guidance. Best practice. Think local.

Leadership, prioritisation and planning as much as 18 months in advance have helped implementation. Effective networks bringing together primary and secondary care make implementation more efficient. Interactive IT can be a powerful tool.

Evidence of a large novel gene pool associated with prokaryotic genomic islands.

Microbial genes that are "novel" (no detectable homologs in other species) have become of increasing interest as environmental sampling suggests that there are many more such novel genes in yet-to-be-cultured microorganisms. By analyzing known microbial genomic islands and prophages, we developed criteria for systematic identification of putative genomic islands (clusters of genes of probable horizontal origin in a prokaryotic genome) in 63 prokaryotic genomes, and then characterized the distribution of novel genes and other features. All but a few of the genomes examined contained significantly higher proportions of novel genes in their predicted genomic islands compared with the rest of their genome (Paired t test = 4.43E-14 to 1.27E-18, depending on method). Moreover, the reverse observation (i.e., higher proportions of novel genes outside of islands) never reached statistical significance in any organism examined. We show that this higher proportion of novel genes in predicted genomic islands is not due to less accurate gene prediction in genomic island regions, but likely reflects a genuine increase in novel genes in these regions for both bacteria and archaea. This represents the first comprehensive analysis of novel genes in prokaryotic genomic islands and provides clues regarding the origin of novel genes. Our collective results imply that there are different gene pools associated with recently horizontally transmitted genomic regions versus regions that are primarily vertically inherited. Moreover, there are more novel genes within the gene pool associated with genomic islands. Since genomic islands are frequently associated with a particular microbial adaptation, such as antibiotic resistance, pathogen virulence, or metal resistance, this suggests that microbes may have access to a larger "arsenal" of novel genes for adaptation than previously thought.

Cancer care. Palliative care. The last days of care.

The government has promised a further 12m pounds over three years for end-of-life care, on top of the 50m pounds a year for palliative care. A framework developed by Macmillan Cancer Relief has identified seven gold standards of care including communication, coordination, control of symptoms, carer support and care in the dying phase. The government has committed to doubling the number of palliative care consultants by 2015.