Change in colony morphology influences the virulence as well as the biochemical properties of theMycobacterium aviumcomplex

Factors that influence colony morphology are of crucial importance for drug development as well as for understanding the virulence ofMycobacterium aviumcomplex (MAC) strains. The MAC 101 strain used in the present study grows as smooth transparent (SmT) colonies that tend to become opaque and pigmented when incubated for long periods of time. However, when MAC was passaged in animals, two types of colonies were recovered. The new rough transparent (RgT) colony morphology appeared more flat and transparent, having a central spot, irregular edges at times, and a dry, granular appearance like that of the rough mutants. In animal studies, the RgT bacilli multiplied at a much faster rate than that of the SmT bacilli, causing 60–80% mortality compared with the 10% mortality observed in mice infected with SmT.In vitrostudies indicated that the SmT MAC did not grow and multiply as well in resident peritoneal macrophages as the RgT MAC did. The two morphotypes did not differ in their growth ratesin vitrobut the RgT MAC failed to reduce dimethylthiazol-diphenyltetrazolium bromide (MTT), alamar blue and neutral red, suggesting that there might be significant changes in the cell wall or elsewhere causing changes in cellular permeability. These two morphotypes could serve as models for studying the biochemical markers or the identification of factors responsible for the virulence of the MAC.     

Comparison of the ex-vivo oral mucosal permeation of tryptophan-leucine (Trp-Leu) and its myristoyl derivative

The ex vivo permeation of a model peptide, tryptophan-leucine (Trp-Leu), was studied using two different regions of pig oral mucosa, the hard palate and the cheek. In order to increase the mucosal absorption of Trp-Leu, a lipophilic derivative was synthesized by acylation of the N-terminal amino group of Trp-Leu with myristic acid. The purified Trp-Leu derivative (Myr-Trp-Leu) was more lipophilic than the parent Trp-Leu as observed by HPTLC (R_f's values of 0.41 and 0.81, respectively). Measurement of partition coefficients in n-octanol/phosphate buffer pH 7.4, gave K_p values of −0.68 and 1.04 for Trp-Leu and Myr-Trp-Leu, respectively. The native Trp-Leu was unable to pass through the keratinized layer of palatal mucosa, and after 24 h only 12% had passed through the buccal mucosa to the receptor compartment. The higher lipophilicity of the acylated peptide, meant that it was not easily transported across the oral mucosal barrier but accumulated in the tissue, founding 25 and 70% of the original amount in the palatal and buccal mucosae, respectively. Both, Trp-Leu and Myr-Trp-Leu were found to be stable in palatal and buccal mucosae.     

Screening asymptomatic adolescent males for chlamydia

Ninety-seven asymptomatic 16–21-year-old sexually active adolescent males were evaluated for gonorrhea and chlamydia by culture, chlamydia enzyme immunoassay, and an analysis of a random urine sample for pyuria using centrifuged urine and urine cytometer. The incidence of gonorrhea was 5.3% and chlamydia by culture 12.3%. Immunoassay was superior in sensitivity and specificity (75% and 99%, respectively) to centrifuged urine (sensitivity 58%, specificity 92%) or urine cytometer (58% and 91%) in identifying asymptomatic chlamydia urethritis. Chlamydia enzyme immunoassay is an acceptable, more rapid, and less expensive alternative to culture. The absence of pyuria in asymptomatic males cannot be assumed to indicate the absence of a sexually transmitted disease.     

Development and validation of a prognostic nomogram model for ICU patients with alcohol-associated cirrhosis

BackgroundThe prognosis of patients with alcohol-associated cirrhosis (ALC) admitted to the intensive care unit (ICU) is poor. We developed and validated a nomogram (NIALC) for ICU patients with ALC.MethodsPredictors of mortality were defined by a machine learning method in a cohort of 394 ICU patients with ALC from the Medical Information Mart for Intensive Care database. Then the nomogram (NIALC) was constructed and evaluated using the AUC. The MELD, MELD-sodium, Child–Pugh, and CLIF-SOFA scores were then compared with NIALC. Two datasets of 394 and 501 ICU patients with ALC were utilized for model validation.ResultsIn-hospital mortality was 41% and 21% in the training and external validation sets. Predictors included were blood urea nitrogen, total bilirubin, prothrombin time, serum creatinine, lactate, partial thromboplastin time, phosphate, mean arterial pressure, lymphocytes, fibrinogen, and albumin. The AUCs for the NIALC were 0.767 and 0.760 in the two validation cohorts, which were better than those of the MELD, MELD-sodium, Child–Pugh, and CLIF-SOFA.ConclusionWe developed a nomogram for ICU patients with ALC, which demonstrated better discriminative ability than previous prognostic scores. This nomogram could be conveniently used to facilitate the individualized prediction of death in ICU patients with ALC.