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: Introduction: There is paucity of data related to potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) among HIV‐positive individuals. We investigated whether such differences exist in the observational D:A:D cohort study. Methods: Participants were followed from study enrolment until the earliest of death, six months after last visit or February 1, 2015. Initiation of CVD interventions [lipid‐lowering drugs (LLDs), angiotensin‐converting enzyme inhibitors (ACEIs), anti‐hypertensives, invasive cardiovascular procedures (ICPs) were investigated and Poisson regression models calculated whether rates were lower among women than men, adjusting for potential confounders. Results: Women (n = 12,955) were generally at lower CVD risk than men (n = 36,094). Overall, initiation rates of CVD interventions were lower in women than men; LLDs: incidence rate 1.28 [1.21, 1.35] vs. 2.40 [2.34, 2.46]; ACEIs: 0.88 [0.82, 0.93] vs. 1.43 [1.39, 1.48]; anti‐hypertensives: 1.40 [1.33, 1.47] vs. 1.72 [1.68, 1.77] and ICPs: 0.08 [0.06, 0.10] vs. 0.30 [0.28, 0.32], and this was also true for most CVD interventions when exclusively considering periods of follow‐up for which individuals were at high CVD risk. In fully adjusted models, women were less likely to receive CVD interventions than men (LLDs: relative rate 0.83 [0.78, 0.88]; ACEIs: 0.93 [0.86, 1.01]; ICPs: 0.54 [0.43, 0.68]), except for the receipt of anti‐hypertensives (1.17 [1.10, 1.25]). Conclusion: The use of most CVD interventions was lower among women than men. Interventions are needed to ensure that all HIV‐positive persons, particularly women, are appropriately monitored for CVD and, if required, receive appropriate CVD interventions., Introduction HIV‐positive individuals are known to be at increased risk of cardiovascular disease (CVD) compared to the general population, partly due to an increased prevalence of some CVD risk factors, [...]

Ganglioside mimicry in the lipopolysaccharide (LPS) fraction of Campylobacter jejuni isolated from Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) patients was compared with isolates from patients with an uncomplicated enteritis. The antibody response to C. jejuni LPS and gangliosides in neuropathy patients and controls was compared as well. LPS from GBS and MFS-associated isolates more frequently contained ganglioside-like epitopes compared to control isolates. Almost all neuropathy patients showed a strong antibody response against LPS and multiple gangliosides in contrast to enteritis patients. Isolates from GBS patients more frequently had a GM1-like epitope than isolates from MFS patients. GQ1b-like epitopes were present in all MFS-associated isolates and was associated with anti-GQ1b antibody reactivity and the presence of oculomotor symptoms. These results demonstrate that the expression of ganglioside mimics is a risk factor for the development of post-Campylobacter neuropathy. This study provides additional evidence for the hypothesis that the LPS fraction determines the antiganglioside specificity and clinical features in post-Campylobacter neuropathy patients. [ABSTRACT FROM AUTHOR]

Lipopolysaccharides (LPS) from Campylobacter jejuni strains isolated from patients with Guillain-Barre syndrome (GBS) display molecular mimicry with GM1. We immunized rabbits with C. jejuni LPS from GBS-associated strains containing a GM1-like epitope. All animals produced high titre anti-LPS antibodies that were cross-reactive with GM1. We conclude that C. jejuni strains from GBS patients are able to induce antibodies that cross-react with gangliosides and LPS. This study further confirms the role of molecular mimicry in the induction of anti-ganglioside antibodies in GBS patients. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) risk factors tend to cluster and interact multiplicatively and have been incorporated into risk equations such as the Framingham risk score, which can reasonably predict CVD over short- and long-term periods. Beyond risk factor levels at a single time point, recent evidence demonstrated that risk trajectories are differentially related to CVD risk. However, factors associated with suboptimal control or unstable CVD risk trajectories are not yet established., Objective: This study aims to examine factors associated with CVD risk trajectories in a semirural, multiethnic community-dwelling population., Methods: Data on demographic, socioeconomic, lifestyle, mental health, and cardiovascular factors were measured at baseline (2013) and during follow-up (2018) of the South East Asia Community Observatory cohort. The 10-year CVD risk change transition was computed. The trajectory patterns identified were improved; remained unchanged in low, moderate, or high CVD risk clusters; and worsened CVD risk trajectories. Multivariable regression analyses were used to examine the association between risk factors and changes in Framingham risk score and predicted CVD risk trajectory patterns with adjustments for concurrent risk factors., Results: Of the 6599 multiethnic community-dwelling individuals (n=3954, 59.92% female participants and n=2645, 40.08% male participants; mean age 55.3, SD 10.6 years), CVD risk increased over time in 33.37% (n=2202) of the sample population, while 24.38% (n=1609 remained in the high-risk trajectory pattern, which was reflected by the increased prevalence of all major CVD risk factors over the 5-year follow-up. Meanwhile, sex-specific prevalence data indicate that 21.44% (n=567) of male and 41.35% (n=1635) of female participants experienced an increase in CVD risk. However, a stark sex difference was observed in those remaining in the high CVD risk cluster, with 45.1% (n=1193) male participants and 10.52% (n=416) female participants. Regarding specific CVD risk factors, male participants exhibited a higher percentage increase in the prevalence of hypertension, antihypertensive medication use, smoking, and obesity, while female participants showed a higher prevalence of diabetes. Further regression analyses identified that Malay compared to Chinese (P<.001) and Indian (P=.04) ethnicity, nonmarried status (P<.001), full-time employment (P<.001), and depressive symptoms (P=.04) were all significantly associated with increased CVD risk scores. In addition, lower educational levels and frequently having meals from outside were significantly associated to higher odds of both worsening and remaining in high CVD risk trajectories., Conclusions: Sociodemographics and mental health were found to be differently associated with CVD risk trajectories, warranting future research to disentangle the role of psychosocial disparities in CVD. Our findings carry public health implications, suggesting that the rise in major risk factors along with psychosocial disparities could potentially elevate CVD risk among individuals in underserved settings. More prevention efforts that continuously monitor CVD risk and consider changes in risk factors among vulnerable populations should be emphasized., (©Hamimatunnisa Johar, Chiew Way Ang, Roshidi Ismail, Zaid Kassim, Tin Tin Su. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 26.09.2024.)

While a congestive heart failure patient will ultimately need an assist device or even a replacement heart as the disease progresses, not every patient is qualified for such advanced therapy. Such patients awaiting better circulatory support benefit from positive inotropes in the meantime as palliative care. These agents are often prescribed in patients with acute decompensated heart failure, with reduced left ventricular ejection fraction and symptoms of organ dysfunction. Although positive inotropes, for example, digoxin, dobutamine, milrinone, levosimendan, etc., are successfully marketed and in use, a lot of their adverse effects, like arrhythmias, hypotension, and even sudden cardiac death, are rather encouraging further research on the development of novel positive inotropes. This review has investigated the molecular mechanisms of some of these adverse effects in terms of the proteins they target, followed by research on newer targets. Studies from 2013-2023 that have reported new small molecules with positive inotropic effects have been revisited in order to determine the progress made so far in drug discovery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The COVID-19 pandemic has led to major changes in the provision of surgical services and also affected patients' health-seeking behaviour. This contributes to delayed presentation of many surgical conditions resulting in poorer outcomes. Colorectal cancer (CRC) patients who present with acute surgical emergencies such as complete bowel obstruction, perforation, bleeding or sepsis often require immediate intervention. This study aimed to assess the impact of COVID-19 pandemic on the proportion of emergency surgery in CRC patients., Materials and Methods: This is a retrospective cohort study. All CRC patients who underwent elective and emergency surgery from January until December 2019 (pre-COVID era) and September 2020 until August 2021 (COVID era) were included. Patient demographics, presentation, tumour stage, surgery performed and waiting time for surgery were collected. Data were then compared., Results: Seventy-seven and 76 new cases of CRC underwent surgery before and during COVID-19, respectively. The proportions of emergency surgery before and during COVID-19 are 29% vs 33% (p=0.562). Of those who required emergency surgery, the proportions of patients who required stoma formation are 59% vs 72% (p= 0.351). There was no difference in median waiting time for patients requiring elective surgery (p= 0.668)., Conclusion: The proportion of emergency surgery for CRC patients is not statistically higher during the pandemic.

Tuberculosis and parasitic infections continue to impose a significant threat to global public health and economic growth. There is an urgent need to develop new treatments to combat these diseases. Here, we report the in vitro and in vivo profiles of a new bicyclic nitroimidazole subclass, namely, nitroimidazopyrazinones, against mycobacteria and Trypanosoma cruzi . Derivatives with monocyclic side chains were selective against Mycobacterium tuberculosis and were able to reduce the bacterial load when dosed orally in mice. We demonstrated that deazaflavin-dependent nitroreductase (Ddn) could act effectively on nitroimidazopyrazinones, indicating the potential of Ddn as an activating enzyme for these new compounds in M. tuberculosis . Oral administration of compounds with extended biaryl side chains ( 73 and 74 ) was effective in suppressing infection in an acute T. cruzi -infected murine model. These findings demonstrate that active nitroimidazopyrazinones have potential to be developed as orally available clinical candidates against both tuberculosis and Chagas disease.

Pretomanid and MCC7433, a novel nitroimidazopyrazinone analog, are promising antitubercular agents that belong to the bicyclic nitroimidazole family. Despite possessing high cell permeability, they suffer from poor aqueous solubility and require specialized formulations in order to be orally bioavailable. To address this limitation, we investigated the use of mesoporous silica nanoparticles (MCM-41) as drug carriers. MCM-41 nanoparticles were synthesized using a sol-gel method, and their surface was further modified with amine and phosphonate groups. A simple rotary evaporation method was used to incorporate the compounds of interest into the nanoparticles, leading to a high encapsulation efficiency of ≥86% with ∼10% loading (w/w). An overall significant improvement of solubility was also observed, and the pharmacological activity of pretomanid and MCC7433 was fully retained when tested in vitro against Mycobacterium tuberculosis using these nanocarriers. Amino-functionalized MCM-41 nanoparticles were found to enhance the systemic exposure of MCC7433 in mice (1.3-fold higher C max ) compared to MCC7433 alone. The current work highlights the potential of using nanoparticles such as mesoporous silica as a carrier for oral delivery of poorly soluble antibacterial agents against tuberculosis.

Hypertension might be a contributing factor of mental illness. The aim of this study was to investigate the association between different levels of hypertension care and mental distress among hypertensive individuals in Malaysia. We constructed a hypertension care cascade using data of 6531 hypertensive individuals aged ≥ 35 years that were collected as part of the community health survey conducted in 2013 in the South East Asia Community Observatory. We examined the association between the status of hypertension care and mental distress using multiple logistic regressions. Respondents who had not been screened for hypertension and those who had uncontrolled blood pressure (BP) had higher odds of depression, anxiety and, stress compared to those who had been screened and those who had controlled BP, respectively. Respondents who were not taking antihypertensive medication had lower odds of depression and anxiety compared to those who were on medication. There was an association between different levels of hypertension care and mental distress. The application of a hypertension care cascade may help improve the provision of mental health support in primary care clinics. Specific mental health interventions could be provided for patients with particular needs along the cascade., (© 2022. The Author(s).)

With the continuous evolution of bacteria, the global antimicrobial resistance health threat is causing millions of deaths yearly. While depending on antibiotics as a primary treatment has its merits, there are no effective alternatives thus far in the pharmaceutical market against some drug-resistant bacteria. In recent years, vaccinology has become a key topic in scientific research. Combining with the growth of technology, vaccine research is seeing a new light where the process is made faster and more efficient. Although less discussed, bacterial vaccine is a feasible strategy to combat antimicrobial resistance. Some vaccines have shown promising results with good efficacy against numerous multidrug-resistant strains of bacteria. In this review, we aim to discuss the findings from studies utilizing reverse vaccinology for vaccine development against some multidrug-resistant bacteria, as well as provide a summary of multi-year bacterial vaccine studies in clinical trials. The advantages of reverse vaccinology in the generation of new bacterial vaccines are also highlighted. Meanwhile, the limitations and future prospects of bacterial vaccine concludes this review., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Despite increasing mortality rates from cardiovascular diseases (CVDs) in low- and middle-income countries, information on the estimation of 10-year CVD risk remains to be sparse. Therefore, this study was aimed at predicting the 10-year CVD risk among community dwellers in Malaysia and at identifying the association of distal (socioeconomic characteristics) and proximal (lifestyle practices) factors with 10-year CVD risk. We calculated the 10-year CVD risk score among 11,897 eligible respondents from the community health survey conducted by the South East Asia Community Observatory (SEACO) using the Framingham risk score (FRS). The findings indicate that 28% of respondents have a high chance of having CVD within the next ten years. After adjusting for the age of respondents, demographic and socioeconomic factors such as gender, ethnicity, marital status, education, income, and occupation had an association with the 10-year CVD risk. In addition, frequent eating out had an association with 10-year CVD risk, while physical activity was found to have no association with predicted CVD risk. CVD remained among the top five mortality causes in Malaysia. Health promotion strategies should emphasize the importance of having home-cooked meals as a healthy dietary behavior, to reduce the mortality rate among Malaysians due to CVDs., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Chiew Way Ang et al.)

A new chemosensor 1 was synthesized by reacting rhodamine B hydrazide and 2,3,4-trihydroxybenzaldehyde, which was then characterized by spectroscopic techniques and single crystal X-ray crystallography. Sensor 1 has the ability to sense Co 2+ /Cu 2+ ions by "naked-eye" with an apparent colour change from colourless to pink in different solvent system, MeCN and DMF respectively. Furthermore, it can selectively detect Co 2+ /Cu 2+ among wide range of different metal ions, and it exhibits low detection limit of 4.425 × 10 -8 M and 1.398 × 10 -7 M respectively. Binding mode of the two complexes were determined to be 1:1 stoichiometry for Co 2+ complex and 1:2 stoichiometry for Cu 2+ complex through Job's plot, IR spectroscopy, mass spectrometry and 1 H NMR spectroscopy. Moreover, reversibility of the sensor 1 as copper (II) ion detector was determined by using EDTA and the results showed that sensor 1 can be reused for at least 6 cycles. Other than that, a low cost chemosensor test strips were fabricated for the convenient "naked-eye" detection of Co 2+ and Cu 2+ in pure aqueous media. The MTT assay was conducted in order to determine the cytotoxicity of sensor 1 towards human cell lines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Following the approval of delamanid and pretomanid as new drugs to treat drug-resistant tuberculosis, there is now a renewed interest in bicyclic nitroimidazole scaffolds as a source of therapeutics against infectious diseases. We recently described a nitroimidazopyrazinone bicyclic subclass with promising antitubercular and antiparasitic activity, prompting additional efforts to generate analogs with improved solubility and enhanced potency. The key pendant aryl substituent was modified by (i) introducing polar functionality to the methylene linker, (ii) replacing the terminal phenyl group with less lipophilic heterocycles, or (iii) generating extended biaryl side chains. Improved antitubercular and antitrypanosomal activity was observed with the biaryl side chains, with most analogs achieved 2- to 175-fold higher activity than the monoaryl parent compounds, with encouraging improvements in solubility when pyridyl groups were incorporated. This study has contributed to understanding the existing structure-activity relationship (SAR) of the nitroimidazopyrazinone scaffold against a panel of disease-causing organisms to support future lead optimization.

Background: Concerns are raised about missed, delayed and inappropriate diagnosis of Lyme Borreliosis. Quantitative descriptive studies have demonstrated non-adherence to the guidelines for testing for Lyme Borreliosis. Objectives: To gain insight into the diagnostic practices that general practitioners apply for Lyme Borreliosis, their motives for ordering tests and how they act upon test results. Methods: A qualitative study among 16 general practitioners using semi-structured interviews and thematic content analysis. Results: Five themes were distinguished: (1) recognising localised Lyme Borreliosis and symptoms of disseminated disease, (2) use of the guideline, (3) serological testing in patients with clinically suspect Lyme Borreliosis, (4) serological testing without clinical suspicion of Lyme Borreliosis, and (5) dealing with the limited accuracy of the serological tests. Whereas the national guideline recommends using serological tests for diagnosing, general practitioners also use them for ruling out disseminated Lyme Borreliosis. Reasons for non-adherence to the guideline for testing were to reassure patients with non-specific symptoms or without symptoms who feared to have Lyme disease, confirmation of localised Lyme Borreliosis and routine work-up in patients with continuing unexplained symptoms. Some general practitioners referred all patients who tested positive to medical specialists, where others struggled with the explanation of the results. Conclusion: Both diagnosis and ruling out of disseminated Lyme Borreliosis can be difficult for general practitioners. General practitioners use serological tests to reassure patients and rule out Lyme Borreliosis, thereby deviating from the national guideline. Interpretation of test results in these cases can be difficult.

Background: Cryptococcal meningitis is most commonly found in HIV-infected patients. In HIV-negative patients, its low incidence can lead to prolonged time to diagnosis. Detailed case reports of chronic cryptococcal meningitis are scarce, but could provide clues for earlier diagnosis in this patient category., Case Presentation: A 60-year old man presented June 2015 with intermittent headaches for several months without any fever. Initial work-up showed a leukocytosis, raised CSF opening pressure and raised leukocytes and protein in the CSF. An MRI revealed leptomeningeal contrast enhancement and cerebellar oedema. While malignancy and various infectious causes were excluded, the patient had a spontaneous clinical and radiological recovery. One year later, the patient returned with complaints of headaches. Also, cerebellar oedema and leptomeningeal contrast enhancement had recurred. Eventually in March 2017, the novel cryptococcal antigen lateral flow assay (CrAg LFA) was positive on CSF, and one colony of Cryptococcus neoformans was cultured from CSF. The patient was treated with the standard antifungal regimen which resulted in resolution of his headaches. In retrospect, the cryptococcal antigen test was already positive on a serum sample from June 2015. Interestingly, post-treatment immunological analysis revealed both a low mannose-binding lectin (MBL) concentration and low naïve CD4 counts., Conclusions: We present a patient with cryptococcal meningitis in an HIV-negative patient with low MBL and low naïve CD4 count suffering a chronic relapsing meningo-encephalitis with relatively mild symptoms for around 2 years. In patients with an unexplained meningo-encephalitis such as this case, early performance of CrAg LFA on serum and/or CSF is an inexpensive and rapid method to reduce time-to diagnosis.

Tuberculosis and parasitic diseases, such as giardiasis, amebiasis, leishmaniasis, and trypanosomiasis, all urgently require improved treatment options. Recently, it has been shown that antitubercular bicyclic nitroimidazoles such as pretomanid and delamanid have potential as repurposed therapeutics for the treatment of visceral leishmaniasis. Here, we show that pretomanid also possesses potent activity against Giardia lamblia and Entamoeba histolytica, thus expanding the therapeutic potential of nitroimidazooxazines. Synthetic analogues with a novel nitroimidazopyrazin-one/-e bicyclic nitroimidazole chemotype were designed and synthesized, and structure-activity relationships were generated. Selected derivatives had potent antiparasitic and antitubercular activity while maintaining drug-like properties such as low cytotoxicity, good metabolic stability in liver microsomes and high apparent permeability across Caco-2 cells. The kinetic solubility of the new bicyclic derivatives varied and was found to be a key parameter for future optimization. Taken together, these results suggest that promising subclasses of bicyclic nitroimidazoles containing different core architectures have potential for further development.

Background: Infection with Borrelia burgdorferi sensu lato complex (B. b. sl) spirochetes can cause Lyme borreliosis, manifesting as localized infection (e.g. erythema migrans) or disseminated disease (e.g. Lyme neuroborreliosis). Generally, patients with disseminated Lyme borreliosis will produce an antibody response several weeks post-infection. So far, no case of neuroborreliosis has been described with persistently negative serology one month after infection., Case Presentation: We present a patient with a history of Mantle cell lymphoma and treatment with R-CHOP (rituximab, doxorubicine, vincristine, cyclofosfamide, prednisone), with a meningo-encephalitis, who was treated for a suspected lymphoma relapse. However, no malignant cells or other signs of malignancy were found, and microbial tests did not reveal any clues, including Borrelia serology. He did not recall being bitten by ticks, and a Borrelia PCR on CSF was negative. After spontaneous improvement of symptoms, he was discharged without definite diagnosis. Several weeks later, he was readmitted with a relapse of symptoms of meningo-encephalitis. This time however, a Borrelia PCR on CSF was positive, confirmed by two independent laboratories, and the patient received ceftriaxone upon which he partially recovered. Interestingly, during the diagnostic process of this exceptionally difficult case, a variety of different serological assays for Borrelia antibodies remained negative. Only P41 (flagellin) IgG was detected by blot and the Liaison IgG became equivocal 2 months after initial testing., Conclusions: To the best of our knowledge this is the first case of neuroborreliosis that is seronegative on repeated sera and multiple test modalities. This unique case demonstrates the difficulty to diagnose neuroborreliosis in severely immunocompromised patients. In this case, a delay in diagnosis was caused by broad differential diagnosis, an absent known history of tick bites, negative serology and the low sensitivity of PCR on CSF. Therefore, awareness of the diagnostic limitations to detect Borrelia infection in this specific patient category is warranted.

Background: Due to the raised public awareness of Lyme Borreliosis (LB), its increased incidence and the increased availability of serological tests, the demand for diagnostic testing on LB has increased. This may affect the diagnostic behaviour of general practitioners (GPs). Aim of our study was to describe GPs' diagnostic behaviour when suspecting LB., Methods: In this descriptive study from January 2010 to June 2015, we used the anonymized electronic medical records of 56,996 patients registered in 12 general practices in Amsterdam, The Netherlands. The target population was identified by means of an extensive search strategy, based on International Classification of Primary Care (ICPC-1) codes, free text and diagnostic test codes. All contacts related to LB were included in the analysis., Results: 2311 patients were included, accounting for 3861 LB contacts and 2619 LB episodes. The distribution of LB contacts showed annual peaks during spring and summer. Serological testing was performed in 36.4% of LB episodes and was mostly requested in patients presenting with general symptoms (71.4%). Unnecessary testing often occurred and only 5.9% of the tests turned out to be positive by immunoblot. From January 2010 to June 2015, no significant differences were found in the number of requested serological tests. The level of serological testing during LB episodes differed significantly between the general practices (19.2% to 75.8%)., Conclusions: Contrary to clinical guidelines, GPs regularly requested serology even when there was a low suspicion of LB. The development of an easy-to-use diagnostic algorithm may decrease overuse of diagnostic tests and thereby reduce overtreatment of LB.

There is no such thing as a perfect diagnostic test and the value of a test depends on the situation in which the test is being used. Here, we discuss two options for dealing with the diagnostic process for Lyme borreliosis in general practice. One option is to manage, treat or refer according to clinical signs and symptoms, in accordance with Dutch practice guidelines. The other option is to use laboratory tests to guide further patient management (treatment or referral). The choice depends on currently unknown factors, such as the pre-test probability of Lyme disease in patients presenting to general practitioners. Furthermore, clarity is required about how to proceed after a positive or negative test result. The consequences of a false test result will depend on the patient's status, possible alternative diagnoses and treatment options. Both physician and patient should be aware of the shortcomings of diagnostic tests.

Objectives: The aim of this verification study was to compare the QuantiFERON ® -TB Gold Plus (QFT-Plus) to the QuantiFERON ® -TB Gold In Tube (QFT-GIT). The new QFT-Plus test contains an extra antigen tube which, according to the manufacturer additionally elicits a CD8 + T-cell response above the CD4 + T-cell response. We assessed the value of this tube in detecting recent latent tuberculosis infections., Methods: Between May 2015 and December 2016, 1031 subjects underwent QFT-Plus and QFT-GIT test. Overall agreement between both tests and performance for different test indications and/or immune states was assessed. A difference of >0.6 IU/mL interferon-γ release between the two antigen tubes of the QFT-Plus assay was considered a true difference and used as estimation for CD8 + T-cell response., Results: Analysis of the QuantiFERON tests resulted in an overall agreement between assays of 95%. Subjects considered to be recently exposed to tuberculosis had significantly more often a true difference in interferon-γ release compared to all other subjects (p = 0.029)., Conclusion: Results of QFT-Plus are highly comparable to QFT-GIT. Although there is an indication that a true difference in interferon-γ release between the antigen tubes is associated with recent latent tuberculosis infection, the QFT-Plus could not be used to exclude recent exposure., (Copyright © 2017. Published by Elsevier Ltd.)

Aim: The clinico-oncological significance of the distance of rectal cancer from the anal verge is unclear and not well reported. The aim of this study is to assess the influence of the rectal cancer distance from the anal verge on clinical management and long-term outcomes after curative resection in a specialised colorectal cancer unit., Methods: Prospectively collected data on patients who underwent primary rectal cancer treatment at our unit between January 2005 and December 2010 were analysed. Low rectal cancer (LRC) was defined as tumour < 5 cm from the anal verge on MRI scan. Recurrent cancer, palliative resections, perforated tumours and those requiring total pelvic exenteration were excluded., Results: Three hundred fifty-nine patients underwent surgery for rectal cancer (226 male/133 female). Of these, 149 (41.5%) patients had low rectal cancer (LRC). Compared to patients with mid/upper rectal cancer (M/URC), patients with low rectal cancers were significantly more likely to receive neo-adjuvant therapy (75.2 vs 38%; p < 0.001), to be associated with lower rate of restorative surgery (15.4 vs 79%; p < 0.001) and to have higher rates of pathological positive circumferential resection margin involvement (14.1 vs 7.1%; p = 0.047). There were however no significant difference in the rates of recurrent disease or survival among the two groups., Conclusion: Distance of rectal cancer from the anal verge does influence the use of neo-adjuvant treatment and ultimate R0 resection rate. It does not influence loco-regional or systemic recurrence rates.

Infectious diseases claim millions of lives every year, but with the advent of drug resistance, therapeutic options to treat infections are inadequate. There is now an urgent need to develop new and effective treatments. Nitroimidazoles are a class of antimicrobial drugs that have remarkable broad spectrum activity against parasites, mycobacteria, and anaerobic Gram-positive and Gram-negative bacteria. While nitroimidazoles were discovered in the 1950s, there has been renewed interest in their therapeutic potential, particularly for the treatment of parasitic infections and tuberculosis. In this review, we summarize different classes of nitroimidazoles that have been described in the literature in the past five years, from approved drugs and clinical candidates to examples undergoing preclinical or early stage development. The relatively "nonspecific" mode of action and resistance mechanisms of nitromidazoles are discussed, and contemporary strategies to facilitate nitroimidazole drug development are highlighted.

A series of novel cholinesterase inhibitors containing nitrobenzoate core structure were synthesized by a facile and efficient method. The structure of the novel compounds were fully characterized and confirmed by analytical as well as spectroscopic methods. Compound indicated as 2f was found to possess the best cholinesterase inhibitory activities of all the evaluated compounds. Results suggest that 2f is a selective acetylcholinesterase inhibitor, although it also inhibits butyrylcholinesterase at higher concentration. Kinetics inhibition result suggest that 2f is a mixed-mode inhibitor of acetylcholinesterase. In addition, it was found to have low cytotoxicity. Molecular docking on compound 2f was carried out to rationalize the observed in vitro enzymatic assay results. Most importantly, the potential of nitrobenzoate derivatives as cholinesterase inhibitor was shown through this study. In summary, we discovered nitrobenzoates as a new scaffold that may eventually yield useful compounds in treatment of Alzheimer's disease., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We describe an 8-month-old girl with diarrhea, urosepsis and hemolytic uremic syndrome caused by Escherichia coli. Typing of cultured E. coli strains from urine and blood revealed the presence of virulence factors from multiple pathotypes of E. coli. This case exemplifies the genome plasticity of E. coli and the resulting heteropathogenic strains.

The epidemiology of Guillain-Barré syndrome (GBS) in tropical areas is different compared with developed countries. We investigated the epidemiology of GBS on the Caribbean island of Aruba. Data were collected retrospectively from all 36 patients hospitalized with GBS between 2003 and 2011 in Aruba. We observed a seasonal distribution of GBS cases with a peak in February. The incidence rate (IR) fluctuated heavily between individual years. The overall IR was 3.93/100,000, which is higher than that observed in developed countries. Serological studies indicated a possible relation of GBS cases with dengue virus infections. We also observed a relation between the annual number of dengue cases in Aruba and the number of GBS cases in the same year. We conclude that the epidemiology of GBS in tropical areas can be different from temperate climate regions and that dengue may be a trigger for developing GBS., (© The American Society of Tropical Medicine and Hygiene.)