Geskus for advice on statistical analysis and Lucy D Phillips fo

Geskus for advice on statistical analysis and Lucy D. Phillips for editorial review. The authors state they have no conflicts of interest to declare. “
“We would like to applaud Chen and colleagues for their recent study of hepatitis B screening data in US travelers attending travel clinics in the Boston area.[1] This article elegantly described how pretravel encounters represent unique opportunities to screen travelers for the most

buy PLX4032 common cause of chronic liver disease worldwide,[2] to identify and educate those infected with the hepatitis B virus (HBV), and to promote vaccination for those found to be susceptible. In their analysis, 48 of 496 travelers with available test results (10%) had antibody to the hepatitis B core antigen (anti-HBc) as the only positive HBV serum marker. The authors describe this test profile as indicative of “possible HBV exposure” without elaborating further. However, we

would like to emphasize that travel health providers taking care of foreign-born travelers from HBsAg high-prevalence areas that are at times also highly prevalent for infection with the human immunodeficiency virus (HIV) and hepatitis C virus (HCV)[2, 3] need to recognize this serological pattern, and understand its clinical implications. Isolated anti-HBc, only rarely

reported (<1%) in HBsAg low-prevalence areas, has been frequently observed (10%–20%) Lck in HBV-endemic countries or in immigrant groups from such countries,[4-6] as well as in individuals coinfected with HIV or HCV.[7] While a false-positive test result has been suggested as a likely explanation for this serological pattern in individuals from HBsAg low-prevalence regions, the “window phase” of acute HBV infection, resolved HBV infection with low or undetectable levels of anti-HBs, or occult chronic HBV infection with low or undetectable HBsAg or mutant HBsAg (that prevents its detection) need to be considered as diagnostic possibilities in immigrants from HBsAg high-prevalence areas.[8] The frequency of occult chronic HBV infection mostly characterized by low-level viremia and no or minimal signs of liver inflammation has been quite variable (0%–40%) depending on the population studied, and its potential for chronic liver disease has been questioned.[8, 9] Yet, significant viral reactivation has been observed in the setting of immunosuppression such as chemotherapy, solid organ/bone marrow transplantation, HIV infection, or antitumor necrosis factor therapy.

e in a fetal medicine unit) has been considered The evidence fr

e. in a fetal medicine unit) has been considered. The evidence from prospective reports of first trimester ART exposure to the APR [7] does not support the need for increased surveillance with the most commonly prescribed therapies (listed in Appendix 4), although with newer medication the knowledge base is inevitably limited. APR reports on the frequency and nature of birth defects and ART are updated every 6 months ( 7.1.2 The combined screening test for trisomy 21 is recommended as this has the best sensitivity and specificity and will minimize the number

of women who may need invasive testing. Grading: 2C Clinical selleck chemical Guidance 62 (CG62) [12] also recommends that all women should be offered screening for trisomy 21. The most effective screening is with the combined test at 11 + 0 to 13 + 6 weeks’ gestation. This includes maternal age, nuchal translucency, βHCG and pregnancy-associated plasma protein A. In the general population this has a detection rate of 92.6% with a false positive rate of 5.2% [13]. For women who present too late for the combined test, the most clinically and cost-effective serum

screening test (triple or quadruple test) should be offered between 15 + 0 and 20 + 0 weeks [12]. However, significantly increased levels of βHCG, α-fetoprotein and lower levels of UE3 (the elements of the ‘triple test’) have been observed in the HIV-positive population [[14][[15][#[16]]Ent]211] while a reduction in βHCG in patients treated with PI-based [17] or with NNRTI-based HAART has been reported. As Down’s syndrome is associated with increased βHCG, theoretically, HIV infection per se may increase the false-positive rate in women and thus increase the number of invasive tests offered compared with the uninfected population. Pregnancy-associated plasma protein A and nuchal Silibinin translucency are unaltered by HIV infection or ART [18] and are thus the preferred screening modality. 7.1.3 Invasive prenatal diagnostic testing should not

be performed until after HIV status of the mother is known and should be ideally deferred until HIV VL has been adequately suppressed. Grading: 1C Limited data suggest amniocentesis is safe in women on HAART. There are minimal data on other forms of prenatal invasive testing. All clinicians performing a prenatal invasive test should know the woman’s HIV status, and if necessary delay the invasive test until the HIV result is available. Where possible, amniocentesis should be deferred until VL is <50 HIV RNA copies/mL. The fetal medicine team should discuss management with an HIV physician if the woman is HIV positive and has a detectable VL. 7.1.4 If not on treatment and the invasive diagnostic test procedure cannot be delayed until viral suppression is complete, it is recommended that women should commence HAART to include raltegravir and be given a single dose of nevirapine 2–4 h before the procedure.


innovative technique mimicking natural conditions


innovative technique mimicking natural conditions, this time used for the microcolony cultivation of uncultivated soil bacteria, is the soil substrate membrane system (Ferrari et al., 2005, 2008), which includes a polycarbonate membrane support and soil extract as a substrate. Although this system allowed the microcultivation of novel bacterial strains, the bacteria remained part of a mixed community on the membrane. A recent development of selleckchem the method has enabled the detection of live microcolonies on the membrane using viability staining, and the subsequent micromanipulation of such colonies for their isolation (Ferrari & Gillings, 2009). The study of bacteria with an obligate intracellular lifestyle presents a particular challenge and it can be difficult to determine and reproduce the environmental conditions required for metabolic Selleck CYC202 activity. For example, initial work investigating the metabolism of Coxiella burnetii used neutral pH buffers and concluded that there was negligible activity (Ormsbee & Peacock, 1964). When acidic buffers were

used, metabolism was markedly enhanced (Hackstadt & Williams, 1981). Further refinements of this approach including the use of a citrate buffer, provision of complex nutrients and high (140 mM) chloride have enabled metabolic activity to be maintained for over 24 h (Omsland et al., 2008), enabling the investigation of the physiology of this important species. Many of the methods described above use an open-ended approach with the aim of cultivating all bacteria present in a sample. As a result, they have led to the cultivation of numerous fastidious bacteria. However, the phylogenetic targeting of specific bacterial strains of interest requires alternative approaches. Advances in molecular biology have enabled the detection and sorting of specific target bacteria with a view to their selective enrichment or physical isolation.

Oligonucleotide probes can be designed to target phylotypes with no known cultivable representatives. Using methods such as FISH or catalysed reporter Calpain deposition (CARD)-FISH for added sensitivity, target-specific probes can detect cells of previously ‘unculturable’ taxa among mixed populations (Amann et al., 1995, 2001; Ferrari et al., 2006; Vartoukian et al., 2009), enabling the visualization of their cellular morphology. A limitation of these methods is that the cells detected within a sample are no longer viable after cell permeabilization and fixation procedures, and may not therefore be subsequently cultured in isolation. The colony hybridization method, on the other hand, is undertaken on membrane transfers from plate cultures that remain viable (Salama et al., 1993). Consequently, hybridization detections on membranes may be used to locate matched microcolonies within mixed cultures, from where they may be isolated. This method has been used in recent work (Vartoukian et al.

Under conditions of high aeration and limiting availability of co

Under conditions of high aeration and limiting availability of combined nitrogen, A. brasilense cells differentiate into aggregating cells and form dense flocs that are visible to the naked eye (Sadasivan & Neyra, 1985; Burdman et al., 1998). Flocs are formed by cell-to-cell aggregation between nonmotile cells embedded in selleck screening library a dense extracellular matrix (Burdman et al., 2000b). Flocculation correlates with, and likely requires the production of, arabinose-rich exopolysaccharides (Bahat-Samet et al., 2004). Scanning electron and fluorescence microscopy studies of A. brasilense aggregating cells indicate the presence of fibrillar

material connecting cells to each other or to biotic or abiotic substrates (Bashan et al., 1986, 1991). These fibrils seem to be absent in nonaggregating cells or mutant strains that are defective in aggregation, suggesting that they may play a role in promoting this behavior (Burdman et Selleckchem Lumacaftor al., 1998; Skvortsov &

Ignatov, 1998). The detailed biochemical composition of this fibrillar material remains unknown, although it is possible that it is related to exopolysaccharide production (Bahat-Samet et al., 2004). In support of this idea, the degree of bacterial aggregation appears to correlate with the amount and composition of exopolysaccharide produced by several A. brasilense strains (Burdman et al., 1998). Chemotaxis is perhaps the most-studied signal transduction pathway in bacteria (reviewed in Sourjik, 2004; Wadhams & Armitage, 2004; Parkinson et al., 2005; Hazelbauer mafosfamide et al., 2008). Despite the identification of homologous chemotaxis systems in phylogenetically distant bacteria and archaeal species, there is a huge diversity in both the number of chemotaxis operons

encoded within bacterial genomes and their physiological roles (Wadhams & Armitage, 2004). Recent studies have shown that the functions of chemotaxis-like pathways are not limited to the regulation of motility patterns, but also include the regulation of biofilm formation, exopolysaccharide production, and cell-to-cell interactions (Black & Yang, 2003; Hickman et al., 2005; Yang & Li, 2005; Caiazza et al., 2007). In prototypical chemotaxis, the histidine kinase CheA and the response regulator CheY form a two-component signal transduction system, which ultimately modulate the probability of changes in the direction of rotation of flagellar motors in response to specific environmental cues. Changes in the phosphorylation of CheY regulated by the CheA–CheY phosphorylation cascade modulate the affinity of CheY for the flagellar motor switch complex and thus chemotaxis. Surprisingly, in A. brasilense, strains carrying mutations in components of the Che1 chemotaxis-like pathway were found to be affected in their ability to interact by cell-to-cell aggregation and in flocculation.

The patient was, therefore, admitted to our hospital for treatmen

The patient was, therefore, admitted to our hospital for treatment, given intravenous infusions and observed for dengue warning signs. The patient’s platelet count was at its lowest on day 7 after onset

of disease (48 × 109/L) and her fever subsided on day 8 after onset. She was discharged after hospitalization for a total of 7 days. DENV-3 genome was detected by real-time polymerase chain reaction (RT-PCR, Applied Biosystems, USA) and virus isolated using the Aedes albopictus mosquito cell line C6/36.[3] Although tests for anti-dengue IgM (Focus Diagnostics, USA), and IgG (Panbio, Australia) antibodies were negative on day 2 after onset of disease, tests using serum sample from day 8 after Nutlin-3a order onset of disease was positive. Both day 2 and day 8 serum samples were positive for dengue NS1 antigen (Platelia, LDK378 in vivo Bio-Rad, France). Serum samples were de-identified prior to being used in the experiments and thus, ethical approval was not required for this study. The nucleotide sequence of the envelope protein (E-protein) of the isolated virus (GenBank accession number AB690858) was compared to selected sequences of DENV-3. The isolated DENV-3 strain from Benin belonged to DENV-3,

genotype III (Figure 1) and had the following characteristics: an E-protein sequence similarity of 99% to the DENV-3 D3/Hu/Côte d’Ivoire/NIID48/2008 strain, 99% to a DENV-3 strain isolated in Senegal in 2009, and 98% to a DENV-3 D3/Hu/Tanzania/NIID08/2010 strain isolated in Tanzania in 2010 (GenBank accession numbers: AB447989, GU189386, and AB549332, respectively). Sporadic cases or outbreaks of DENV infection have been reported in 34 countries in the African region. It is estimated Miconazole that 2.4% of global dengue hemorrhagic fever (DHF) cases (100,000 cases) and up to 1 million cases of DF may occur in Africa.[2] Among travel-associated dengue cases in travelers returning to Europe, 2 to 8% had visited Africa.[2, 5] In comparison, most of

the travelers returning to Europe with dengue had traveled to Asia (54–61%) and Latin America (25–31%). Febrile illness was, however, more frequently reported in 41% of travelers to sub-Saharan Africa (2,559 patients) as compared to other regions (Southeast Asia, 33%, 1,218 patients; Caribbean and Central and South America, 18%, 1,044 patients).[9] Although dengue is frequently reported in travelers to Southeast Asia and South America as compared to Africa, the disease may be underreported in Africa due to limited awareness of the disease, and, limited availability of diagnostic tests and routine surveillance system.[2] Imported cases of DENV type-3 infection from West Africa have been previously reported in European travelers.[2-6] The first possibility of DENV circulation in Benin was suggested by a seroprevalence study conducted in asymptomatic Germans working overseas from 1987 to 1993.

Using a ‘pre-packaged to take out’ (pre-pack TTO) medicines syste

Using a ‘pre-packaged to take out’ (pre-pack TTO) medicines system in a clinical area with a high patient turnover has the potential to reduce discharge time and increase this website bed capacity allowing for new admissions. This evaluation aims to measure the benefits of the system. The service improvement project was implemented in September 2013 on an acute surgical ward in accordance with the requirements set out by the Trust’s medicines and discharge policies.1 Every patient’s discharge prescription was analysed during October 2013 and March 2014 to evaluate

the impact of the project. In addition, discharge prescriptions dispensed by Pharmacy during this time were also analysed for comparison. Ethics committee approval was not needed. (a)  Cost comparison: TTO pre packs’; are 17% more expensive than standard original packs, however when Pharmacy costs are taken into account, the differences are negligible. The average number of items per discharge is 1.6 items for those supplied

on the ward and 4.3 for those dispensed by Pharmacy, providing assurance that more complex discharges are being dispensed by Pharmacy to ensure patient safety in line with Trust policy. The increase in proportion of discharges completed using ‘TTO pre packs’; (59% to 73%) indicates that this process is effective. A comparison of the time taken clearly shows that patients suitable for ward based supply can leave hospital 125 minutes sooner than if medication was dispensed by Pharmacy. This is the equivalent of 30.7 full bed days, or assuming a cost of £250 per bed per patient per day* this equates Dabrafenib to £90k per year of bed space that could be utilised in a more effective and efficient manner. This evaluation does not take into account how many prescriptions a Pharmacist clinically screened, or the nursing resources required to ensure consistent provision of this service. 1. Procedure for the supply of pre-labelled discharge medicine packs by nursing staff against a prescription, ** Hospitals

Trust, July 2011 M. J. Boyda, H. F. Boardmanb, A. Joshuac aDivision for Social Research in Medicines and Health, The School of Pharmacy, University of Nottingham,, Nottingham, PJ34 HCl UK, bInnovation in Pharmacy Education Division, The School of Pharmacy, University of Nottingham,, Nottingham, UK, cNHS England, NHS 111 National Programme, Redditch, UK Analysis of pharmacist records of queries to NHS Direct aimed to determine the nature of medicine related issues. NHS Direct pharmacists handled a large number of queries from patients and carers despite other services being available. Many queries relating to medicines are about acute medicines issues. Pharmacists have provided advice to patients for centuries. NHS Direct was launched as a service in 1998 by the then government and provided a radical new option in health care delivery, a 24 hour telephone advice line, free at the point of use. NHS Direct handled hundreds of thousands of calls every month on many aspects of care.

Because of their small genomes, mycoplasmas are commonly chosen a

Because of their small genomes, mycoplasmas are commonly chosen as model organisms for the study of the minimal gene set needed to support the growth of free-living bacteria and are ideal for dissecting the role of individual genes in pathogenesis. The most comprehensive work has been performed with Mycoplasma genitalium. Using transposon mutagenesis, 387 of the 480 protein-coding regions and all of the 37 genes coding for RNA species were identified Selleckchem BIBW2992 as essential for the growth of M. genitalium (Glass et al., 2006). Because of the lack of gene duplication and the absence of redundant pathways,

it should be expected that the 580-kb genome of M. genitalium would have more essential genes than a bacterium with a large genome such as Bacillus subtilis, a Gram-positive bacterium to which the mycoplasmas are phylogenetically related. Indeed, only 271 of the 4100 genes of B. subtilis are thought to be essential (Kobayashi et al., 2003). Mycoplasma pulmonis is a pathogen of rats and mice and the etiological agent of murine respiratory mycoplasmosis (Lindsey & Cassell, 1973). In an earlier study of a transposon library of M. pulmonis, 321 of the 782 protein-coding regions were identified as dispensable for growth (French et al., 2008). The criteria used to consider a gene to be inactivated were that at least 10% of the coding region from the annotated 5′ start site or at least 15% of the coding region from the 3′ end would be

truncated. The size of the library was large enough to conclude that nonessential genes >1 kb were inactivated. The previous studies relied on Tn4001T, which transposes actively in the mycoplasmal Crizotinib genome. A more recent study in Mycoplasma arthritidis made use of the Tn4001TF1 minitransposon, derived from Tn4001 (Dybvig et al., 2008). The minitransposon readily transposed into the genome, but

once inserted, was unable to undergo subsequent Tryptophan synthase transposition events. This minitransposon was applied to M. pulmonis in the current study. The use of the minitransposon generated a superior library with inactivation of 39 genes that were previously thought to be essential. Mycoplasma pulmonis strain CT (Davis et al., 1986) was propagated in mycoplasma broth (MB) and mycoplasma agar (MA) as described (Dybvig et al., 2000; Simmons & Dybvig, 2003). CT was transformed with plasmid pTF85, carrying minitransposon Tn4001TF1 (Dybvig et al., 2008), using 36% polyethylene glycol and selecting for resistance to tetracycline as described (Dybvig et al., 2000). Individual colonies were picked, grown in 1 mL MB and stored at −80 °C as described (French et al., 2008). The genomic location of the transposon was determined for each library member by DNA sequence analysis of an inverse PCR product containing the junction between the transposon and the adjacent mycoplasmal DNA using primers and reaction conditions as described (Teachman et al., 2002; French et al., 2008).

Biofilm EPS can contain polysaccharides, proteins, nucleic acids

Biofilm EPS can contain polysaccharides, proteins, nucleic acids (Flemming & Wingender, 2002), but few specific reports exist on the EPS matrix of P. putida biofilms. As a first approach to address the increased biofilm formation by the TOL-carrying strain, we attempted to extract EPS from biofilm-containing stagnant liquid cultures by a standard protocol using a cation-exchange resin (Frølund et al., 1996). However, it was not possible to extract the EPS component that caused the higher viscosity: both extracts had similar low viscosities [KT2440: 1.3 cSt Pexidartinib in vivo vs. KT2440 (TOL) 1.8 cSt], and extractable carbohydrate and nucleic acid contents were similar for both strains (Table 3).

This suggested that a major part of the EPS was not extractable and remained cell associated. Further attempts to increase Forskolin extraction intensities rapidly caused cell lysis, as observed by rRNA release in extracts (results not shown). Consequently, we attempted to analyze EPS components directly in the biofilm-containing liquid cultures. Total carbohydrate contents were about double as high as in the extracts, but no striking differences between the two strains were found. Total DNA contents of the two cultures were, however, clearly different: The TOL-carrying strain contained twice the amount of total DNA, as compared with the respective plasmid-free cultures, as similar cellular biomass contents measured as particulate protein. The next approach

involved direct visualization by microscopy. To check for the differential presence of eDNA in liquid–solid interface biofilms, 7-day-old flow cell biofilms of the TOL-free or TOL-carrying KT2440 were stained with propidium iodide (PI). Diffuse PI fluorescence

was colocalized with the larger (presumably older) microcolonies formed by the TOL-carrying strain, indicating that eDNA was a major Cobimetinib price constituent (Fig. 1). The plasmid-free strains, again, did not form thick biofilms, and eDNA was not observed. Using similar approaches, eDNA has been observed in various pure-culture biofilms (e.g. Pseudomonas aeruginosa, Bacillus subtilis, Enterococcus faecalis, environmental isolate) (Whitchurch et al., 2002; Bockelmann et al., 2006; Thomas et al., 2009; Vilain et al., 2009), and eDNA is, therefore, increasingly being considered a potential core element of the biofilm matrix. eDNA has similarly been observed in flocs and unsaturated biofilms of environmental Pseudomonas (Palmgren & Nielsen, 1996; Steinberger & Holden, 2005). In contrast to our observations, this eDNA remained easily extractable by chemical or thermal treatment methods isolates (Palmgren & Nielsen, 1996; Steinberger & Holden, 2005). Ultimately, eDNA was successfully extracted from TOL-free and TOL-carrying KT2440 cultures by enzymatic treatment using cellulase and proteinase K followed by centrifugation (Wu & Xi, 2009), without concurrent increase in cell lysis as ascertained using live/dead cell staining.

Based on observational studies [6,15–19] and expert opinion, curr

Based on observational studies [6,15–19] and expert opinion, current US guidelines recommend immunization of patients with PPV-23 when CD4 counts are above 200 cells/μL [20], whereas the World Health Organization (WHO) states that the pneumococcal polysaccharide vaccine may be considered for people with HIV infection in WHO clinical stage 1 or, if CD4 testing is available, with a CD4 count above 500 cells/μL [21]. However, study quality and the risk of bias in these studies have not been assessed. Following the recent success of 7-valent pneumococcal conjugate vaccine in preventing vaccine serotype-specific IPD in a cohort consisting primarily of HIV-infected Malawian adolescents [22],

a critical evaluation of PPV-23 effectiveness is needed. Immunity against capsulated bacteria such as pneumococci AZD2281 manufacturer depends on the formation of opsonic antibodies, which can be produced by B cells in response to polysaccharide stimulation. These antigens are classified as T-cell independent type 2 (TI-2) antigens, as they active B cells directly without assistance from T

cells [23]. Untreated HIV-infected subjects buy Nintedanib have reduced antibody responses to PPV-23 [8], which correlate with falling CD4 cell counts [24,25]. HAART partially restores the immune system by reducing HIV replication and immune activation, and improving CD4 cell counts. However, certain abnormalities of the immune system persist even years after HAART initiation, including a low CD4:CD8 ratio, a low naïve:memory cell ratio, expansion of CD28 effector T cells and a reduced T cell repertoire [26]. HAART may affect qualitative aspects of the PPV-23 response by restoring the expression of certain genes used in the PPV-23 response to normal levels and by improving the specific immunoglobulin G response to vaccines, including PPV-23 [11–13,27,28]. Thus, when assessing PPV-23 effectiveness in persons with HIV infection, it

selleckchem should be borne in mind that the effects of CD4 cell count and HAART treatment may be important. A number of risk factors for pneumococcal disease have been identified over the past 20 years (Table 1). Awareness of these risk factors is critical in the assessment of PPV-23 studies because, unless adjusted for in the statistical analysis, any risk factor for pneumococcal disease may potentially confound the measurement of vaccine effectiveness. CD4 cell count is an example of a well-known risk factor for pneumonia and pneumococcal disease [4,6,16,17,29–31]. Other risk factors related to progression of HIV infection are HIV RNA [4,30,32,33] and clinical disease stage [16,17,29]. The aim of this review was to systematically identify and critically assess all peer-reviewed and non-peer-reviewed literature on observational studies and clinical trials of the effectiveness of PPV-23 in terms of clinical endpoints in HIV-infected adults.

In the case of the latter drug, it may be particularly appropriat

In the case of the latter drug, it may be particularly appropriate for use in the obese Omipalisib solubility dmso subject with GDM. “
“Structured education programmes support and enable people with diabetes to develop self-management skills. Insulin management central to DAFNE is restricted to those with type 1 diabetes of at least six months’ duration and on

multiple dose regimens. DESMOND is available for all with type 2 diabetes but does not include guidance on how to self-manage diabetes with insulin. Our aims were to develop an education programme for people with type 1 or 2 diabetes already on insulin and who may be using a variety of insulin regimens, to enable effective self-management, improve confidence, reduce hypoglycaemia and enable peer group support. An evidence-based curriculum, developed in line with NICE principles, was piloted. This consisted of three half-day Sirolimus ic50 sessions held during a one-month period with up to 10 participants and supporters invited to attend. Four further programmes were held; education was tailored to the individual needs of groups and verbal evaluation was undertaken. Anonymised patient satisfaction questionnaires

were posted at programme completion. Audit included clinical data, demographics, patient satisfaction and health care professional assessment of content. There were 40 participants Etoposide datasheet over five courses; 20% (n=8) were type 1, 68% (n=27) were male, average age was 58 years (range 35–82 years), and 55% were South Asian (n=22). In 38 of 40 participants where a recorded pre- and three months post-intervention was available, an average HbA1c reduction of 1.18% was achieved – i.e. 9.02% reduced to 7.84% (75.1mmol/mol

reduced to 62.2mmol/mol). Twenty-five participants (62.5%) returned the survey form: 96% (24/25) said diabetes control improved, and all felt more confident to adjust insulin; 96% (23/24) felt more confident to treat ‘hypos’ (one stated ‘hypos’ had not reduced) and 96% (24/25) felt they learned more by attending the programme. This programme met participants’ individual needs, increased confidence in insulin management and improved glycaemic control in a high ethnic mix poulation. Copyright © 2014 John Wiley & Sons. Practical Diabetes 2014; 31(2): 54–57 “
“The central theme of this article is that a person with diabetes who thinks they are ‘not good enough’ at diabetes self-management is manifesting a sense of shame. This fundamental human attribute is often the most significant, underlying issue that people face in psychotherapy and yet neither the ICD-10 nor the DSM-V recognises shame as a discrete diagnosis.