Parasite Survival and Disease Persistence in Cystic Fibrosis, Schistosomiasis and Pathogenic Bacterial Diseases: A Role for Universal Stress Proteins?

Universal stress proteins (USPs) were originally discovered in Escherichia coli over two decades ago and since then their presence has been detected in various organisms that include plants, archaea, metazoans, and bacteria. As their name suggests, they function in a series of various cellular responses in both abiotic and biotic stressful conditions such as oxidative stress, exposure to DNA damaging agents, nutrient starvation, high temperature and acidic stress, among others. Although a highly conserved group of proteins, the molecular and biochemical aspects of their functions are largely evasive. This is concerning, as it was observed that USPs act as essential contributors to the survival/persistence of various infectious pathogens. Their ubiquitous nature in various organisms, as well as their augmentation during conditions of stress, is a clear indication of their direct or indirect importance in providing resilience against such conditions. This paper seeks to clarify what has already been reported in the literature on the proposed mechanism of action of USPs in pathogenic organisms.

Early prediction of prostate cancer biochemical recurrence and identification of disease persistence using PSA isoforms and human kallikrein-2

BACKGROUND: The role of isoforms of prostate specific antigen (PSA) and other kallikrein-related markers in early detection of biochemical recurrence (BCR) after radical prostatectomy (RP) is not well known and serum PSA is currently used in preoperative risk nomograms. OBJECTIVE: The aim of this research was to study pre- and early postoperative levels of important PSA isoforms and human kallikrein-2 to determine their ability to predict BCR and identify disease persistence (DP). METHODS: This study included 128 consecutive patients who underwent RP for clinically localized prostate cancer. PSA, fPSA, %fPSA, [–2]proPSA, PHI and hK2 were measured preoperatively, at 1 and 3 months after RP. We determined the ability of these markers to predict BCR and identify DP. RESULTS: The DP and BCR rate were 11.7%and 20.3%respectively and the median follow up was 64 months (range 3–76 months). Preoperatively, the independent predictors of BCR were PSA (p-value 0.029), [–2]proPSA (p-value 0.002) and PHI (p-value 0.0003). Post-RP, PSA was the single marker correlating with BCR, both at one (p-value 0.0047) and 3 months (p-value 0.0004). PSA, fPSA, [–2]proPSA and PHI significantly correlated to DP at 1 and 3 months post-RP (p-value < 0.05), although PSA had the most significant existing correlation (p-value < 0.0001). CONCLUSIONS: [–2]proPSA and PHI are preoperative predictors of BCR and DP that outperform the currently used serum PSA. At the early postoperative period there is no additional benefit of the other markers tested.

TgAb’s Change Trend and Degree of Decline Has Good Prognostic Value for Preoperative TgAb-Positive DTC Patients: A Retrospective Study in Southwest China

PurposeAntithyroglobulin antibody (TgAb) is a potential tumor marker for the detection of recurrence of DTC, but there are not sufficient data supporting its application in clinical work. Our study aimed at describing change trend of TgAb after surgery and finding the relationship between this trend and clinical outcome of DTC.MethodsWe reviewed clinical data of 583 patients initially diagnosed with thyroid malignancy and underwent total thyroidectomy (TTx) in our hospital in 2016. Finally, 21 preoperative TgAb-positive DTC patients with persistent disease were included in Group A, and 37 preoperative TgAb-positive DTC patients survived without disease were included in Group B. Various clinical indicators and TgAbs at different timepoints were compared between two groups.ResultsIn all 538 patients, 21.27% had preoperative TgAb positive (>115IU/mL), of which 16.94% survived with disease persistence/recurrence. Tumor, lymph node classification, and preoperative TgAb were significantly higher in Group A than B (P<0.05). TgAb of 23.81% patients in Group A became negative, and 89.19% in B. Compared with Group B, change trend of TgAb of Group A was more inclined stable or rising after surgery. Of patients with descending TgAb in Group A, their declines at first follow-up (40.75% vs 79.77%), the first year (76.67% vs 88.01%), the second year (80.00% vs 91.72%) after surgery were significantly lower than Group B (P<0.05). And the best cut-off values of three declines of TgAb for predicting clinical outcome were 43.32%, 72.81% and 84.36% respectively. Patients’ clinical outcome was significantly associated with tumor classification T1a (OR=145.661, 95%CI: 2.462-8619.550) and TgAb decline at first follow-up (OR=158.858, 95%CI: 7.440-3392.024).ConclusionsFor preoperative TgAb-positive DTC patients, stable or rising trend of TgAb after surgery or TgAb decline less than 43.43% before the RRA or 6 months after surgery may predict disease persistence/recurrence.

Mating-Type and Sexual Differentiation of Phytophthora Colocasiae in Japan

In Japan, Phytophthora colocasiae causes the leaf blight of taro, which has resulted in huge losses since 2015. To investigate the causes of disease persistence and expansion, it is important to clarify the basic properties of this pathogen. We collected in total 317 P. colocasiae isolates from 99 fields in 7 prefectures during 2014 to 2020. The mating-type of each isolate was examined, and two or more isolates which were collected in single fields or taro leaves were selected to analyze the mating-type complexity. We found five kinds of mating types were identified: heterothallic A1 and A2, self-fertile (SF) A1, A2 and A1/A2 types, and a complex and diverse distribution of mating-types was present in one field or leaf. In addition, the stability of each mating-type was analyzed by single hyphae, zoospore and zoosporangium. The results suggested that the SF isolates were shown to be genetically unstable, while heterothallic isolates had a stable property. In the pathogenicity test of different mating-type isolates, heterothallic A1 isolates were less pathogenic than heterothallic A2 and SF isolates. However, there was no relationship between the pathogenicity and the growth rate on culture medium.

Current Indications of Secondary Enucleation in Retinoblastoma Management: A Position Paper on Behalf of the European Retinoblastoma Group (EURbG)

Secondary enucleation (SE) puts an irreversible end to eye-preserving therapies, whenever their prolongation is expected to violate the presumed state of metastatic grace. At present, it must be acknowledged that clear criteria for SE are missing, leading to empiric and subjective indications commonly related to disease progression or relapse, disease persistence masking the optic nerve head or treatment-related complications obscuring the fundus view. This absence of evidence-based consensus regarding SE is explained by the continuously moving frontiers of the conservative management as a result of diagnostic and therapeutic advances, as well as by the lack of studies sufficiently powered to accurately stratify the risk of metastasis in conservatively treated patients. In this position paper of the European Retinoblastoma Group (EURbG), we give an overview of the progressive shift in the indications for SE over the past decades and propose guidelines to assist decision-making with respect to when SE becomes imperative or recommended, with corresponding absolute and relative SE indications. Further studies and validation of biologic markers correlated with the risk of metastasis are expected to set more precisely the frontiers of conservative management and thus consensual criteria for SE in the future.

Predictive Value of Gross Extranodal Extension for Differentiated Thyroid Carcinoma Persistence/Recurrence

Objective We systematically investigated the predictive value of gross extranodal extension (gENE) for differentiated thyroid carcinoma persistence/recurrence. Study Design Retrospective study. Setting A tertiary care hospital. Methods This study was divided into 2 groups according to gENE status: the gENE group and non-gENE group. We compared the disease persistence/recurrence rates of these 2 groups in the entire cohort and by individual risk group (intermediate/high risk), analyzed whether gENE was an independent risk factor for disease persistence/recurrence, and explored the impact of gENE-specific features on disease persistence/recurrence. Results There were 989 patients who satisfied the inclusion criteria: 57 patients in the gENE group and 932 in the non-gENE group. The disease persistence/recurrence rate of the gENE group was higher than that of the non-gENE group in the entire cohort and by individual risk group ( P < .05 for each). Unexpectedly, the outcomes of the gENE group with intermediate risk were similar to those of the non-gENE group with high risk ( P = .72). For the entire cohort, gENE was an independent predictor for disease persistence/recurrence (odds ratio, 2.89; 95% CI, 1.39-6.00; P = .005). Specific features of gENE ( P > .05 for each) were not related to disease persistence/recurrence. Conclusion Patients with gENE and intermediate risk might be regraded as high risk. Specific features of gENE have no impact on disease persistence/recurrence.

First but not second postoperative day growth hormone assessments as early predictive tests for long-term acromegaly persistence

Purpose Postoperative assessment of acromegaly activity is typically performed at least 3 months after neurosurgery (NS). Few studies have evaluated the use of early postoperative growth hormone (GH) levels as a test to predict short- and long-term remission of acromegaly. Our objective was to evaluate the diagnostic performance of serum random GH on a postoperative day one (D1-rGH) and two (D2-rGH), particularly in predicting long-term disease persistence. Materials and methods Forty-one subjects with acromegaly who were undergoing NS were enrolled (mean age ± SD 47.4 ± 13.1 years at diagnosis; women 54%; macroadenomas 71%). The final assessment of disease activity was performed one year after NS. ROC curves were used to evaluate the diagnostic performance of D1-rGH and D2-rGH. Results After a 1-year follow-up, the overall remission rate was 55%. ROC analysis identified an optimal D1-rGH cut-off value of 2.1 ng/mL for diagnosing long-term disease persistence (55.6% SE; 90.9% SP). The cut-off point became 2.5 ng/mL after maximizing specificity for disease persistence (yielding a 100% positive predictive value) and 0.3 ng/mL after maximizing sensitivity for disease remission. The optimal D2-rGH cut-off value was 0.6 ng/mL (81.8% SE; 50% SP); the cut-off point became 2.9 ng/mL after maximizing specificity and 0.1 ng/mL after maximizing sensitivity, with no clinical utility. Conclusions D1-rGH could be a highly specific test for the early diagnosis of long-term acromegaly persistence, which is predicted by a value > 2.5 ng/mL with a great degree of certainty. The diagnostic performance of D2-rGH was insufficient. Further research is required to validate these preliminary results prior to modifying the postoperative management of acromegaly.

Dynamics of an infection age-space structured cholera model with Neumann boundary condition

This paper investigates global dynamics of an infection age-space structured cholera model. The model describes the vibrio cholerae transmission in human population, where infection-age structure of vibrio cholerae and infectious individuals are incorporated to measure the infectivity during the different stage of disease transmission. The model is described by reaction–diffusion models involving the spatial dispersal of vibrios and the mobility of human populations in the same domain Ω ⊂ ℝ n . We first give the well-posedness of the model by converting the model to a reaction–diffusion model and two Volterra integral equations and obtain two constant equilibria. Our result suggest that the basic reproduction number determines the dichotomy of disease persistence and extinction, which is achieved by studying the local stability of equilibria, disease persistence and global attractivity of equilibria.

A Stochastic Differential Equations Model for the Spread of Coronavirus COVID-19): The Case of Iraq

In this paper, we model the spread of coronavirus (COVID -19) by introducing stochasticity into the deterministic differential equation susceptible -infected-recovered (SIR model). The stochastic SIR dynamics are expressed using Itô's formula. We then prove that this stochastic SIR has a unique global positive solution I(t).The main aim of this article is to study the spread of coronavirus COVID-19 in Iraq from 13/8/2020 to 13/9/2020. Our results provide a new insight into this issue, showing that the introduction of stochastic noise into the deterministic model for the spread of COVID-19 can cause the disease to die out, in scenarios where deterministic models predict disease persistence. These results were also clearly illustrated by Computer simulation.