The blisters and erosions can occur as a result of trauma but may

The blisters and erosions can occur as a result of trauma but may also arise spontaneously36 and can be exacerbated by sweating and warmer climates33. Other findings include milia, dystrophy, or absence of nails, alopecia, exuberant granulation tissue, congenital absence of skin, palmoplantar keratoderma, mottled pigmentation, and pigmented naevi26. Secondary skin lesions are cutaneous atrophy, scarring, pigmentary abnormalities, webbing and contractures (Images 30–32)26. EB and cutaneous squamous cell carcinoma:  Squamous cell carcinoma (SCC) of the skin is one of the most severe complications of EB, starting to arise in early adulthood in patients with the severe forms of EB, notably RDEB. SCC

can present as a nonhealing, crusted erosion with little or no palpable dermal component, selleck chemicals similar to other wounds on

the skin, or mimic areas of granulation tissue26 (Image 33). Ocular findings in EB:  The most common ocular findings in patients with EB include corneal blisters and erosions, corneal scarring, pannus formation, limbal broadening, conjunctival blisters and erosions, symblepharon, eyelid blisters and scars, ectropion, and lacrimal duct obstruction. Marked visual impairment can result from repeated injury to the cornea, especially if scarring develops26. HDAC inhibitor Ear, nose, and throat in EB:  Signs and symptoms in the upper respiratory tract in patients with EB can include weak or hoarse cry, dysphonia, inspiratory stridor, soft tissue oedema, vesiculation or blistering of all tracheolaryngeal structures and ulceration, thickening and scarring of the true and false vocal cords26. Dysphagia and oesophageal strictures:  EB-associated strictures may arise anywhere in the oesophagus and vary in length

and shape (Image 34). Over time, intra-luminal bullae, web formation, and strictures result in progressive dysphagia with all its consequences, including severe malnutrition, growth impairment, and the risk of aspiration and pneumonia. Dysphagia can present as early as 10 months, with an average of onset at 48 ± 34 months95. Lower gastrointestinal tract complications: The most common lower gastrointestinal complaint is chronic constipation in patients with the more severe EB subtypes26. Malnutrition:  Nutritional compromise is directly proportional to the severity of EB and occurs mainly in generalized form of recessive dystrophic EB PAK6 (RDEB) and junctional EB96–98. Acral deformities:  Pseudosyndactyly is the most visible extracutaneous complication of inherited EB and is primarily seen in RDEB. These progressive deformities can cause marked functional disability (Images 35 and 36)26. Anaemia:  Anaemia occurs in patients with severe EB, particularly RDEB-HS and JEB-H. In most patients, the anaemia is multifactorial in origin. Contributing factors include chronic blood, iron, and protein loss from open wounds on the skin and poor intake and gastrointestinal absorption of iron and other nutrients26.

24 vs 013, respectively;

24 vs. 0.13, respectively; Pirfenidone P=0.0001). A significantly greater increase from baseline in mean ApoA1 was observed in NVP patients than in ATZ/r patients at each visit from week

4 to week 48. At week 48, there was a significantly greater mean increase in ApoA1 in the combined NVP arm compared with the ATZ/r arm (P<0.0001). In contrast, changes in mean ApoB levels from baseline to week 48 were minor regardless of the treatment arm. When the mean change from baseline to week 48 in the ApoB:ApoA1 ratio was considered, a greater decrease was observed in the combined NVP group than in the ATZ/r group (P=0.008). Percentage changes in lipid parameters are presented in Table 1. Only 17 patients took lipid-lowering agents during this study (nine in the combined NVP group and eight in the ATZ/r group). One patient in the ATZ/r group was treated with anion-exchange resins, two in each group were treated with fibrates, and all other patients were treated with statins. In analyses of lipid data, all data collected

after patients started lipid-lowering medications were excluded, consistent with the predefined analysis plan. A higher proportion of patients in the combined NVP group had elevated (≥200 mg/dL) TC than those in the ATZ/r group, whereas elevated TG levels (≥150 mg/dL) were more common in the ATZ/r group (Table 2). The proportion of patients with HDL-c ≥40 mg/dL was significantly higher in the combined NVP arm than in the ATZ/r arm at every time-point from Selleck Baf-A1 week 4 onwards (Fig. 2a).

Similarly, the proportion of patients with LDL-c ≥130 mg/dL Selleckchem Sirolimus was higher than that for ATZ/r at all time-points during treatment (Fig. 2b). Mean baseline values for SBP were similar between the combined NVP and ATZ/r groups (119.5 and 120.1 mmHg, respectively). The mean change from baseline to week 48 (LOCF) in SBP was greater in the NVP group than in the ATZ/r group (3.1 vs. 0.4 mmHg, respectively; P=0.031 from post hoc analyses, not significant after adjustment for multiple testing). Baseline values for diastolic blood pressure were similar between the combined NVP and ATZ/r groups (74.3 and 74.4 mmHg, respectively). The mean change from baseline to week 48 (LOCF) in diastolic blood pressure was greater in the NVP group than in the ATZ/r group (2.7 vs. 1.0 mmHg, respectively; P=0.045 from post hoc analyses, not significant after adjustment for multiple testing). Baseline values for the estimated cardiovascular risk score according to the Framingham algorithm [6] were similar between the combined NVP group and the ATZ/r group (3.09 vs. 2.81, respectively). The change from baseline to week 48 (LOCF) in the estimated cardiovascular risk score according to the Framingham algorithm was similar between the groups (0.70 for NVP combined and 0.80 for ATZ/r; difference −0.069; 95% CI −0.60 to 0.46; P=0.80).

The South African clawed frog epithelial cells (XTC-2) were grown

The South African clawed frog epithelial cells (XTC-2) were grown in Leibovitz L-15 (Gibco) medium supplemented with 10% NBC (Gibco), 0.4% tryptose phosphate broth (Oxoid, UK) and 1% L-glutamine (Gibco) and incubated at 28 °C in 5% CO2. Six 24-well trays (IWAKI, Japan) each containing the four cell culture types were grown to confluency. Each well contained

2 mL of medium. Dilutions 10−6–10−11 (Arandale isolate) or 10−5–10−10 (Henzerling buy PD0332991 strain) were used to infect the cell cultures. Six wells of each cell culture type were inoculated with 100 μL of each dilution of C. burnetii. Cultures were incubated for 6 weeks before the monolayer from each well was harvested by scraping. Cells were pelleted by centrifugation for 5 min at 4500  g and resuspended in 300 μL of phosphate-buffered saline (PBS; Selleckchem BGB324 Oxoid) and analysed by DNA extraction and Com1 PCR. The DNA

was extracted from 200 μL by Qiagen Extraction Kit (Qiagen, Germany), following the manufacturers’ instructions, eluted into 50 μL and analysed by specific PCR targeting a 76-bp sequence of the com1 gene (Lockhart et al., 2011). Extracted DNA (5 μL) was analysed for each reaction. The cycling threshold resulting form the PCR was used to calculate the approximate C. burnetii DNA concentration (μg μL−1) in each reaction. The C. burnetii dose that would infect 50% of cultures (ID50) was calculated using the Spearman–Kärber method (Anellis & Werkowski,

1968). The dilutions of the inoculum were analysed by PCR, and a standard curve was made (data not shown) and used to convert the ID50 calculation from a dilution into a number of bacterial copies required for 50% infection. By determining which wells contained C. burnetii DNA in amounts to suggest growth of the bacteria, the ID50 could be determined for each cell line and C. burnetii isolate. The cell line most susceptible (sensitive) to infection was different for the two C. burnetii isolates (Table 1). Thalidomide For the Arandale isolate the Vero cell line was the most sensitive with an ID50 of 0.1 copies of C. burnetii, followed by the L929 cell line with an ID50 of 3.2 copies. For the Henzerling strain, the DH82 cell line was the most sensitive with an ID50 of 14.6 copies of C. burnetii followed by the L929 cell line with an ID50 of 22.0 copies. Number of C. burnetii (copy numbers per 100 μL) required for 50% infection of cell line Number of C. burnetii (copy numbers per 100 μL) required for 50% infection of cell line During the growth of C. burnetii the monolayers were routinely observed under light microscopy. Only in Veros could infection with C. burnetii be seen as large vacuoles in the cell cytoplasm.

, 2005), whereas other studies have reported that AMR and VGs are

, 2005), whereas other studies have reported that AMR and VGs are only weakly linked, if at all (Johnson et al., 2003). Recently, some studies investigating antibiotic resistance in relation to phylogenetic origin have found that resistance to ampicillin, tetracycline, chloramphenicol, streptomycin, extended-spectrum cephalosporins, cephamycins, and sulfonamides was

associated with decreased virulence traits among human clinical E. coli isolates (Johnson et al., 2003; Moreno et al., 2006), whereas resistance was not associated with decreased GSI-IX cell line virulence traits among animal E. coli isolates (Johnson et al., 2003). However, there is no conclusive evidence to indicate whether resistance to antimicrobials is associated with differences in the prevalence of certain VGs in swine E. coli isolates. Therefore, we investigated the prevalence of AMR phenotypes, virulence factors, and phylogenetic groups of E. coli isolates.

Specifically, we explored whether AMR and virulence traits among E. coli isolates from diseased pigs were significantly associated. Numerous diseased or dead animals were submitted to the Veterinary Research Institute, www.selleckchem.com/products/i-bet-762.html Guangdong Academy of Agricultural Sciences, for diagnostic investigation. For our study, we selected all the E. coli isolates in this collection that came from pigs with diarrhea or edema disease between March 2002 and May 2008. These diseased animals were housed on 58 farms all over Guangdong Province. Each of the farms typically housed approximately 5000 animals. Between one and six herds were sampled from each farm, and each sample was from an individual animal. Isolates were recovered from rectal swabs of 2–10-week-old diseased piglets as well as from the intestinal contents of dead piglets. All E. coli organisms were isolated and purified on MacConkey agar. The bacterial strains were identified using classical biochemical Selleckchem Lonafarnib methods and confirmed using the API-20E system (bioMérieux, France). All confirmed E. coli isolates were

stored at −80 °C in Luria–Bertani broth medium containing 10% glycerol. Antimicrobial susceptibility testing was performed on all 167 E. coli isolates using the microdilution broth method according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI) (2004). As there are no CLSI breakpoints for doxycycline that are applicable to E. coli of animal origin, the breakpoints of doxycycline (≥16 mg L−1) were referred to Clinical and Laboratory Standards Institute (CLSI) (2008) document M100-S18 for isolates of human origin. The reference strain, E. coli ATCC 25922, was used as a quality control strain for determining the minimum inhibitory concentrations of 12 antimicrobial agents (Table 1). All isolates were assigned to one of the four main phylogenetic groups of E. coli (A, B1, B2, and D) by multiplex PCR, as described by Clermont et al. (2000).

8%) over a 1-year period In a 6-month study, Heelon et al [3] f

8%) over a 1-year period. In a 6-month study, Heelon et al. [3] found 73 HAART errors in 41 patients (21% of hospitalized patients with HIV infection), most of which were the result of incomplete regimens. In our study, 21.7% of HIV-infected patients admitted and prescribed antiretroviral therapy had at least one prescription-related problem. These results are similar to those of Rastegar et al. and Heelon et al. The most commonly

observed problems are inappropriate dosage and ICG-001 drug–drug interactions. Mok et al. [4] found that, among 251 prescriptions for antiretroviral agents, the dosage was inappropriate in 57 cases (37 excessive and 20 insufficient), accounting for 32.4% of all detected problems. The lack of an adjustment for renal Pifithrin-�� in vivo insufficiency was also considered an excessive dosage; this happened on 19 occasions. Forty-six drug–drug interactions were identified (26.1% of all detected problems); 36 of the 83 patients included in the review (43.4%) had an incomplete antiretroviral regimen (20.4% of all problems detected). Dosage error was also the most common type of error detected by Rastegar et al. [14] (34 admissions;

16.3%); 18 of these errors were inappropriate dosage adjustment in patients with renal insufficiency. The next most common error was contraindicated combinations (12 admissions; 5.2%), followed by receiving two or fewer antiretroviral agents (eight cases; 3.8%). In seven admissions (3.3%) there was an unexplained delay in continuing HAART. Gray et al. [15] analysed the causes of HIV medication

errors in MEDMARX, a voluntary database reporting many inpatient medication errors. They found that the most common causes of error were inappropriate dosing (38%), followed by incorrect medication (32%). In our study, interactions caused by contraindicated or not recommended drug–drug combinations (33.3%) were slightly higher than in the study by Mok et al. [4]. We found that, in total, dose-related problems (incorrect dose, dose omission, and lack of dose adjustment in patients with renal or hepatic impairment) accounted for 43.3% of all errors. This result is comparable to those of Mok et al. [4] and Gray et al. [15] Risk factors associated with a HAART-related error in our study were similar to those found by Mok et al. [4]: renal impairment, an atazanavir-containing regimen, and admission by a service other than the infectious diseases service. We also found that receiving a nonnucleoside reverse transcriptase inhibitor was a protective factor. There is abundant evidence that antiretroviral drug-related errors on admission are frequent and may be of clinical relevance. Clinical pharmacists with training in HIV pharmacotherapy can play an important role in correcting such errors. They should closely monitor prescriptions to identify problems and resolve them as soon as possible in order to prevent toxicity or drug resistance.

The treatment optimism beliefs included: ‘New treatments for HIV

The treatment optimism beliefs included: ‘New treatments for HIV have brought hope for a cure’; ‘HIV will soon be a controllable disease like diabetes’; and ‘There will be a cure for HIV in the next Seliciclib few years’. A six-point scale was used for responses to questions about infectiousness beliefs and treatment optimism, with 1 indicating ‘strongly disagree’ and 6 indicating ‘strongly agree’. Mean scores were computed for both infectiousness beliefs (α=0.77) and treatment optimism (α=0.66). The AUDIT consists of 10 items designed to identify risks for alcohol abuse and dependence

[26]. The first three items of the AUDIT represent the quantity and frequency of alcohol use and the remaining seven items concern problems arising from drinking alcohol. AUDIT scores range from 0 to 40, with scores of ≥8 indicating high risk for problem drinking. This scale is an abbreviated version of the original DAST, designed to identify drug-use-related problems in the past year [27]. The DAST is internally consistent and has demonstrated time stability and acceptable sensitivity

and specificity in detecting drug abuse. Scores range from 0 to 10. We examined IDH inhibitor factors associated with having recently been diagnosed with an STI among men and women living with HIV/AIDS. Participants who had been diagnosed with an STI during the 6-month window were compared with those who did not have an STI in that time period using logistic regressions, reporting odds ratios, 95% confidence intervals and significance. We also tested for differences between STI groups in sexual behaviours, infectiousness beliefs and HIV treatment optimism in analyses that included current viral load as a moderating variable. Specifically, we conducted STI diagnosis (not having had a recent STI or having

had a recent STI) × viral load (detectable, undetectable or not known) analyses of variance with sexual behaviours entered as the dependent variables. These 2 × 3 analyses of variance yielded main effects for having had a recent STI diagnosis and viral load, and the interaction between recent STI diagnosis and viral load. A multivariate analysis was subsequently performed in which all factors found to differ between STI groups at the P<0.05 level of significance in the univariate analyses were entered. We used multivariate logistic regression to simultaneously enter variables 3-oxoacyl-(acyl-carrier-protein) reductase in a model differentiating participants who did not have a recent STI and those who had been diagnosed with an STI. Because sexual behaviours were highly skewed, we transformed these variables using the formula log10(X+1). Statistical significance was defined as P<0.05. Among the 490 participants, 51 (10%) reported having been diagnosed with an STI in the past 3 months at the initial assessment and 19 (4%) had been diagnosed in the subsequent 3 months, yielding a total of 70 (14%) HIV-positive men and women reporting STI diagnoses in the 6-month window.

The question is how to interpret the many findings in terms of pa

The question is how to interpret the many findings in terms of pathogenic mechanism at play in vivo, and thus in non-overexpression conditions. It remains uncertain whether the cleavage, phosphorylation and ubiquination of TDP-43 are important for pathogenicity or not. Propensity

of TDP-43 to aggregate, further enhanced by the presence of mutations, is an almost universal finding (Johnson et al., 2009; Nonaka et al., 2009; Zhang et al., 2009), although the most relevant model generated hitherto did not contain TDP-43-containing aggregates (Wegorzewska et al., 2009). Furthermore, the significance INCB024360 chemical structure of the depletion of TDP-43 from the nucleus (found in many but not in all studies) as an underlying ‘compartmental’ loss-of-function

mechanism needs to be established. Alternatively, the sequestering of TDP-43 in the cytoplasm may be the underlying gain-of-function mechanism. Does cytoplasmic TDP-43 gain a toxic biochemical function? Is the formation of aggregates, or one of the (oligomeric) species that are a step in the dynamics of this process, the mechanism of disease? Are essential cellular constituents trapped into these aggregates, resulting in an ‘unrelated’ loss of function? In summary, the finding of TDP-43 in ALS and FTLD neurons and the identification of TDP-43 mutations in familial ALS was a second leap forward in ALS research. It has drawn attention to the possible role of RNA processing in the pathogenic

mechanism of these diseases, even though the involvement of RNA in the mechanism itself ABT 737 remains to be demonstrated (Lemmens et al., 2010). Of major importance is of course the possible involvement of TDP-43 in sporadic ALS. It looks as if TDP-43 may play a role similar to α-synuclein in Parkinson’s disease (PD) and amyloid precursor protein (APP) in Alzheimer’s disease (AD). α-Synuclein mutations are a rare cause of familial PD, and α–synuclein-containing inclusions are seen in the sporadic form of click here PD. APP mutations are a rare cause of AD, but abnormally processed APP under the form of Aβ is a hallmark of sporadic AD. APP and α-synclein overexpression give rise to AD and PD in humans. This has not been observed for TDP-43 in ALS yet. Finally, it needs to be pointed out that, while TDP-43-containing aggregates are seen in the large majority of sporadic ALS patients, they were noted to be absent in many (Mackenzie et al., 2007; Robertson et al., 2007; Tan et al., 2007), but not all (Shan et al., 2009) studies on mutant SOD1 ALS. This may suggest that the mechanisms underlying mutant SOD1-induced motor neuron degeneration and that of sporadic ALS may be different. This still needs to be studied in depth but it has further fuelled the doubts about whether mutant SOD1 models are of use in studying sporadic ALS.

Xylella fastidiosa can be graft transmitted to healthy plants or

Xylella fastidiosa can be graft transmitted to healthy plants or vectored by several species selleck screening library of xylem-feeding leafhoppers (Redak et al., 2004). Antimicrobial peptides (AMPs) are defensive substances widespread in nature, being produced from bacteria to mammals (Sang & Blecha, 2008). The majority display common features such as a low molecular

mass, a positive net charge at physiological pH and an amphipathic structure (Bulet et al., 2004). Generally, AMPs disrupt the plasmatic membrane, causing the rapid death of microorganisms. Nevertheless, some AMPs can cross the microbial membrane acting on internal cellular targets (Brogden, 2005). The elucidation of the exact mode of action of AMPs is essential to allow the use of these substances to develop a new generation of antibiotics to control infections of both plants and animals. Gomesin is a short β-hairpin AMP (2270.4 Da) isolated from the hemocytes of the tarantula spider Acanthoscurria gomesiana (Silva et al.,

2000). Similar to Venetoclax cell line most AMPs, gomesin is cationic and possesses an amphipatic structure (Mandard et al., 2002). Bacteria and fungi synthesize and secrete AMPs to inhibit the growth of neighboring microorganisms that compete for both space and nutrients (Sang & Blecha, 2008). Several bacteria and fungi species have been reported to compose an endophytic community that cohabits the xylem vessels of citrus plants along with X. fastidiosa (Araujo et al., 2002). Moreover, many tissues of insects, including salivary glands and the lining epithelial cells, produce AMPs to prevent infection (Bulet et al., 2004). Therefore, it is likely that X. fastidiosa may be exposed to AMPs during colonization of both the host plant and the insect vector. To verify whether and how X. fastidiosa would respond to AMPs, we evaluated the effect of gomesin on its global gene expression profile and on Thymidylate synthase X. fastidiosa colonization success of

tobacco plants. Ampicillin, streptomycin and tetracycline were from Sigma-Aldrich (St. Louis, MO). Gomesin (Silva et al., 2000) was synthesized as described previously (Fazio et al., 2006). Lyophilized gomesin and conventional antibiotic were reconstituted in sterile deionized water immediately before use. Virulent 9a5c and avirulent J1a12 X. fastidiosa strains (Li et al., 1999; Koide et al., 2004) were grown in periwinkle wilt (PW) broth medium (Davis et al., 1981) supplemented with 20% glucose as described previously (Zaini et al., 2008). Mid-log suspensions (OD600 nm=0.400) of either 9a5c or J1a12 strains were incubated with different concentrations of gomesin (0.14–9 μg mL−1), ampicillin (0.31 × 103–5 × 103 μg mL−1), streptomycin (0.19–100 μg mL−1), tetracycline (0.97–500 μg mL−1) or water as control. After 18 h at 28 °C, cells were harvested by centrifugation at 4000 g for 5 min at 25 °C, suspended in fresh PW medium and plated on 2% agar PW.

Xylella fastidiosa can be graft transmitted to healthy plants or

Xylella fastidiosa can be graft transmitted to healthy plants or vectored by several species TSA HDAC cell line of xylem-feeding leafhoppers (Redak et al., 2004). Antimicrobial peptides (AMPs) are defensive substances widespread in nature, being produced from bacteria to mammals (Sang & Blecha, 2008). The majority display common features such as a low molecular

mass, a positive net charge at physiological pH and an amphipathic structure (Bulet et al., 2004). Generally, AMPs disrupt the plasmatic membrane, causing the rapid death of microorganisms. Nevertheless, some AMPs can cross the microbial membrane acting on internal cellular targets (Brogden, 2005). The elucidation of the exact mode of action of AMPs is essential to allow the use of these substances to develop a new generation of antibiotics to control infections of both plants and animals. Gomesin is a short β-hairpin AMP (2270.4 Da) isolated from the hemocytes of the tarantula spider Acanthoscurria gomesiana (Silva et al.,

2000). Similar to www.selleckchem.com/products/Bleomycin-sulfate.html most AMPs, gomesin is cationic and possesses an amphipatic structure (Mandard et al., 2002). Bacteria and fungi synthesize and secrete AMPs to inhibit the growth of neighboring microorganisms that compete for both space and nutrients (Sang & Blecha, 2008). Several bacteria and fungi species have been reported to compose an endophytic community that cohabits the xylem vessels of citrus plants along with X. fastidiosa (Araujo et al., 2002). Moreover, many tissues of insects, including salivary glands and the lining epithelial cells, produce AMPs to prevent infection (Bulet et al., 2004). Therefore, it is likely that X. fastidiosa may be exposed to AMPs during colonization of both the host plant and the insect vector. To verify whether and how X. fastidiosa would respond to AMPs, we evaluated the effect of gomesin on its global gene expression profile and on 4-Aminobutyrate aminotransferase X. fastidiosa colonization success of

tobacco plants. Ampicillin, streptomycin and tetracycline were from Sigma-Aldrich (St. Louis, MO). Gomesin (Silva et al., 2000) was synthesized as described previously (Fazio et al., 2006). Lyophilized gomesin and conventional antibiotic were reconstituted in sterile deionized water immediately before use. Virulent 9a5c and avirulent J1a12 X. fastidiosa strains (Li et al., 1999; Koide et al., 2004) were grown in periwinkle wilt (PW) broth medium (Davis et al., 1981) supplemented with 20% glucose as described previously (Zaini et al., 2008). Mid-log suspensions (OD600 nm=0.400) of either 9a5c or J1a12 strains were incubated with different concentrations of gomesin (0.14–9 μg mL−1), ampicillin (0.31 × 103–5 × 103 μg mL−1), streptomycin (0.19–100 μg mL−1), tetracycline (0.97–500 μg mL−1) or water as control. After 18 h at 28 °C, cells were harvested by centrifugation at 4000 g for 5 min at 25 °C, suspended in fresh PW medium and plated on 2% agar PW.

17–19 Ultimately, the purpose of the predeployment education is t

17–19 Ultimately, the purpose of the predeployment education is to prepare the trainees for the worse case scenario. In the event of a high-risk exposure, regardless of HIV status confirmation, immediate administration of PEP is warranted. With subsequent confirmation of HIV status through available Ribociclib solubility dmso testing, adherence to the PEP regimen is

paramount. Initiation of PEP should be immediate (ideally within 24 h) and continued for 4 weeks.20 In addition, the regimen chosen must balance potential toxicities against the level of exposure and the burden of disease (as characterized by the CD4 cell count, viral load, disease stage, and viral resistance) of the source patient. Unfortunately, Enzalutamide nmr PEP regimens are frequently discontinued due to intolerance of side effects, despite their known benefit in terms of reduction

of risk of HIV infection.8 Side effects can often be easily managed symptomatically with over-the-counter medications such as analgesics, antiemetics, and antimotility agents. The most basic PEP regimen recommended in the US Public Health Service guidelines includes either a combination of two nucleoside reverse transcriptase inhibitors (eg, zidovudine plus lamivudine or emtricitabine) or a nucleotide reverse transcriptase inhibitor with a nucleoside reverse transcriptase inhibitor (eg, tenofovir with either lamivudine or emtricitabine).8 Similarly, the WHO recommends zidovudine/lamivudine as the first-line therapy.21 The fixed dose combination of tenofovir/emtricitabine is generally better tolerated than zidovudine–lamivudine.18 Both guidelines recommend the addition of a protease inhibitor, with lopinavir/ritonavir listed PRKACG as the first-line option, for more severe exposures.8,13 The 200/50 mg formulation of lopinavir/ritonavir is preferred because this does not require refrigeration. Alternate

protease inhibitors for the expanded regimen include ritonavir plus atazanavir or ritonavir plus darunavir.8,20 However, the ritonavir used in the latter two regimens requires refrigeration, which may not be feasible for traveling medical trainees. The newly available tablet form of ritonavir does not require refrigeration, in contrast to the gel capsule formulation. Efavirenz can be added to the basic regimen instead of a protease inhibitor, but this drug should not be used for PEP in pregnant health care workers or those who are planning to conceive during the month of treatment. In contrast, due to safety issues, nevirapine is contraindicated for PEP.