Toll-like receptors in ischaemia and its potential role in the pathophysiology of muscle damage in critical limb ischaemia

Toll-like receptors (TLRs) are key receptors of the innate immune system which are expressed on immune and nonimmune cells. They are activated by both pathogen-associated molecular patterns and endogenous ligands. Activation of TLRs culminates in the release of proinflammatory cytokines, chemokines, and apoptosis. Ischaemia and ischaemia/reperfusion (I/R) injury are associated with significant inflammation and tissue damage. There is emerging evidence to suggest that TLRs are involved in mediating ischaemia-induced damage in several organs. Critical limb ischaemia (CLI) is the most severe form of peripheral arterial disease (PAD) and is associated with skeletal muscle damage and tissue loss; however its pathophysiology is poorly understood. This paper will underline the evidence implicating TLRs in the pathophysiology of cerebral, renal, hepatic, myocardial, and skeletal muscle ischaemia and I/R injury and discuss preliminary data that alludes to the potential role of TLRs in the pathophysiology of skeletal muscle damage in CLI.

The Emerging Role of TLR and Innate Immunity in Cardiovascular Disease

Cardiovascular disease is a complex disorder involving multiple pathophysiological processes, several of which involve activation of toll-like receptors (TLRs) of the innate immune system. As sentinels of innate immunity TLRs are nonclonally germline-encoded molecular pattern recognition receptors that recognize exogenous as well as tissue-derived molecular dangers signals promoting inflammation. In addition to their expression in immune cells, TLRs are found in other tissues and cell types including cardiomyocytes, endothelial and vascular smooth muscle cells. TLRs are differentially regulated in various cell types by several cardiovascular risk factors such as hypercholesterolemia, hyperlipidemia, and hyperglycemia and may represent a key mechanism linking chronic inflammation, cardiovascular disease progression, and activation of the immune system. Modulation of TLR signaling by specific TLR agonists or antagonists, alone or in combination, may be a useful therapeutic approach to treat various cardiovascular inflammatory conditions such as atherosclerosis, peripheral arterial disease, secondary microvascular complications of diabetes, autoimmune disease, and ischemia reperfusion injury. In this paper we discuss recent developments and current evidence for the role of TLR in cardiovascular disease as well as the therapeutic potential of various compounds on inhibition of TLR-mediated inflammatory responses.

The role of adjuvant hormonal treatment after surgery for localized high-risk prostate cancer: results of a matched multiinstitutional analysis

Introduction. To assess the role of adjuvant androgen deprivation therapy (ADT) in high-risk prostate cancer patients (PCa) after surgery. Materials and Methods. The analysis case matched 172 high-risk PCa patients with positive section margins or non-organ confined disease and negative lymph nodes to receive adjuvant ADT (group 1, n = 86) or no adjuvant ADT (group 2, n = 86). Results. Only 11.6% of the patients died, 2.3% PCa related. Estimated 5-10-year clinical progression-free survival was 96.9% (94.3%) for group 1 and 73.7% (67.0%) for group 2, respectively. Subgroup analysis identified men with T2/T3a tumors at low-risk and T3b margins positive disease at higher risk for progression. Conclusion. Patients with T2/T3a tumors are at low-risk for metastatic disease and cancer-related death and do not need adjuvant ADT. We identified men with T3b margin positive disease at highest risk for clinical progression. These patients benefit from immediate adjuvant ADT.

Sense and nonsense of an extended pelvic lymph node dissection in prostate cancer

Lymph node metastases associated with prostate cancer (PCa) has been shown to be a poor prognostic factor. The role of pelvic lymph node dissection (PLND) itself in relation to survival remains unclear, however. A Medline search was conducted to address this issue. The following conclusions were drawn. Only recently, improved survival due to completion of radical prostatectomy (RP) (compared to abandoning RP) in known or presumed lymph-node-positive patients has been shown. Lymph node sampling can only be considered representative if an adequate number of nodes is removed. While several authors have suggested that a therapeutic benefit in patients undergoing RP is not provided by PLND, the reliability of these studies is uncertain. Contrary to this, several studies have indicated the possibility of long-term survival even in the presence of limited lymph node metastases. The role and timing of initiation of adjuvant androgen deprivation therapy (ADT) in patients who have node-positive disease after RP is controversial. Recent studies suggest that delaying ADT may not adversely impact survival.

Controversies in the treatment of ingrown nails

Ingrown toenails are one of the most frequent nail disorders of young persons. They may negatively influence daily activities, cause discomfort and pain. Since more than 1000 years, many different treatments have been proposed. Today, conservative and surgical methods are available, which, when carried out with expertise, are able to cure the disease. Packing, taping, gutter treatment, and nail braces are options for relatively mild cases whereas surgery is exclusively done by physicians. Phenolisation of the lateral matrix horn is now the safest, simplest, and most commonly performed method with the lowest recurrence rate. Wedge excisions can no longer be recommended.

Medication errors in a swiss cardiovascular surgery department: a cross-sectional study based on a novel medication error report method

The purpose of this study was (1) to determine frequency and type of medication errors (MEs), (2) to assess the number of MEs prevented by registered nurses, (3) to assess the consequences of ME for patients, and (4) to compare the number of MEs reported by a newly developed medication error self-reporting tool to the number reported by the traditional incident reporting system. We conducted a cross-sectional study on ME in the Cardiovascular Surgery Department of Bern University Hospital in Switzerland. Eligible registered nurses (n = 119) involving in the medication process were included. Data on ME were collected using an investigator-developed medication error self reporting tool (MESRT) that asked about the occurrence and characteristics of ME. Registered nurses were instructed to complete a MESRT at the end of each shift even if there was no ME. All MESRTs were completed anonymously. During the one-month study period, a total of 987 MESRTs were returned. Of the 987 completed MESRTs, 288 (29%) indicated that there had been an ME. Registered nurses reported preventing 49 (5%) MEs. Overall, eight (2.8%) MEs had patient consequences. The high response rate suggests that this new method may be a very effective approach to detect, report, and describe ME in hospitals.

The Validation of a New Visual Anaemia Evaluation Tool HemoHue HH1 in Patients with End-Stage Renal Disease

In chronic haemodialysis patients, anaemia is a frequent finding associated with high therapeutic costs and further expenses resulting from serial laboratory measurements. HemoHue HH1, HemoHue Ltd, is a novel tool consisting of a visual scale for the noninvasive assessment of anaemia by matching the coloration of the conjunctiva with a calibrated hue scale. The aim of the study was to investigate the usefulness of HemoHue in estimating individual haemoglobin concentrations and binary treatment outcomes in haemodialysis patients. A prospective blinded study with 80 hemodialysis patients comparing the visual haemoglobin assessment with the standard laboratory measurement was performed. Each patient's haemoglobin concentration was estimated by seven different medical and nonmedical observers with variable degrees of clinical experience on two different occasions. The estimated population mean was close to the measured one (11.06 ± 1.67 versus 11.32 ± 1.23 g/dL, P < 0.0005). A learning effect could be detected. Relative errors in individual estimates reached, however, up to 50%. Insufficient performance in predicting binary outcomes (ROC AUC: 0.72 to 0.78) and poor interrater reliability (Kappa < 0.6) further characterised this method.

Manipulation of energy transfer processes in nanochannels

The realisation of molecular assemblies featuring specific macroscopic properties is a prime example for the versatility of supramolecular organisation. Microporous materials such as zeolite L are well suited for the preparation of host-guest composites containing dyes, complexes, or clusters. This short tutorial focuses on the possibilities offered by zeolite L to study and influence Förster resonance energy transfer inside of its nanochannels. The highly organised host-guest materials can in turn be structured on a larger scale to form macroscopic patterns, making it possible to create large-scale structures from small, highly organised building blocks for novel optical applications.

Investigations on an egyptian coffin and mummified head from Burgdorf Museum, Switzerland - A case of a historical puzzle

In the Burgdorf Museum of Ethnology, a mummy rests in a coffin. According to the inventory book, it was purchased from the Cairo Egyptian museum in 1926. The coffin was now examined by Egyptologists and the mummy was radiocarbon dated and examined by Anthropologists. The aim of the study was to compare the results and to check whether mummy and coffin actually belong together. The skull was examined morphological-anthropologically and by CT as a “blank sample”. Coffin and skull imply that the individual was female. The coffin dates to the Ptolemaic period. Only skull bones are preserved, the ethmoid is damaged. CT images Show resinous substances, bone fragments and brain remnants inside the skull. The ethmoid bone was probably foraminated during the mummification process and thus ended up inside the skull. The individual was mummified between the New Kingdom and the Ptolemaic period. Due to its style, it is most probable that the coffin comes from the Gamhud necropolis. The Burgdorf museum of ethnology inventory book chronicles were largely falsified by the examinations. There is a time gap between coffin and the mummy, there are two possible interpretations: the body was mummified with older linen, or the mummy and the coffin do not belong together. The authors strongly advise further investigations.

Congenital factor XIII deficiency in Pakistan: characterization of seven families and identification of four novel mutations

Deficiency of coagulation factor XIII (FXIII) belongs to the rare bleeding disorders and its incidence is higher in populations with consanguineous marriages. The aims of this study were to characterize patients and relatives from seven families with suspected FXIII deficiency from Pakistan and to identify the underlying mutations. As a first indicator of FXIII deficiency, a 5M urea clot solubility test was used. Plasma FXIII A- and B-subunit antigen levels were determined by ELISA. FXIII activity was measured with an incorporation assay. Sequencing of all exons and intron/exon boundaries of F13A was performed, and a novel splice site defect was confirmed by RT-PCR analysis. Genetic analysis revealed six different mutations in the F13A gene. Two splice site mutations were detected, a novel c.1460+1G>A mutation in the first nucleotide of intron 11 and a previously reported c.2045G>A mutation in the last nucleotide of exon 14. Neither of them was expressed at protein level. A novel nonsense mutation in exon 4, c.567T>A, p.Cys188X, was identified, leading in homozygous form to severe FXIII deficiency. Two novel missense mutations were found in exons 8 and 9, c.1040C>A, p.Ala346Asp and c.1126T>C, p.Trp375Arg, and a previously reported missense mutation in exon 10, c.1241C>T, p.Ser413Leu. All patients homozygous for these missense mutations presented with severe FXIII deficiency. We have analysed a cohort of 27 individuals and reported four novel mutations leading to congenital FXIII deficiency.

Revolution to Revolution: Tracing Egyptian Public Art from Saad Zaghloul to January 25

Artists have spent a century claiming Egypt for the Egyptians. Now the powerful murals of January 25 have created a new public space dedicated to every citizen.