HIV/AIDS-Pneumonia Codynamics Model Analysis with Vaccination and Treatment

In this paper, we proposed and analyzed a realistic compartmental mathematical model on the spread and control of HIV/AIDS-pneumonia coepidemic incorporating pneumonia vaccination and treatment for both infections at each infection stage in a population. The model exhibits six equilibriums: HIV/AIDS only disease-free, pneumonia only disease-free, HIV/AIDS-pneumonia coepidemic disease-free, HIV/AIDS only endemic, pneumonia only endemic, and HIV/AIDS-pneumonia coepidemic endemic equilibriums. The HIV/AIDS only submodel has a globally asymptotically stable disease-free equilibrium if R 1 < 1 . Using center manifold theory, we have verified that both the pneumonia only submodel and the HIV/AIDS-pneumonia coepidemic model undergo backward bifurcations whenever R 2 < 1 and R 3 = max R 1 , R 2 < 1 , respectively. Thus, for pneumonia infection and HIV/AIDS-pneumonia coinfection, the requirement of the basic reproduction numbers to be less than one, even though necessary, may not be sufficient to completely eliminate the disease. Our sensitivity analysis results demonstrate that the pneumonia disease transmission rate β 2 and the HIV/AIDS transmission rate β 1 play an important role to change the qualitative dynamics of HIV/AIDS and pneumonia coinfection. The pneumonia infection transmission rate β 2 gives rises to the possibility of backward bifurcation for HIV/AIDS and pneumonia coinfection if R 3 = max R 1 , R 2 < 1 , and hence, the existence of multiple endemic equilibria some of which are stable and others are unstable. Using standard data from different literatures, our results show that the complete HIV/AIDS and pneumonia coinfection model reproduction number is R 3 = max R 1 , R 2 = max 1.386 , 9.69 = 9.69 at β 1 = 2 and β 2 = 0.2 which shows that the disease spreads throughout the community. Finally, our numerical simulations show that pneumonia vaccination and treatment against disease have the effect of decreasing pneumonia and coepidemic disease expansion and reducing the progression rate of HIV infection to the AIDS stage.

The Role of Internal Limiting Membrane as a Biomarker in the Evolution of Myopic Traction Maculopathy

Purpose: To describe the longitudinal structural changes of myopic traction maculopathy (MTM) based on optical coherence tomography (OCT) and to detect biomarkers in the evolution of MTM.Methods: A retrospective study was conducted on patients with MTM as defined by OCT. A minimum follow-up of 6 months was necessary for study inclusion. The effects of comprehensive OCT-based structure on the evolution of MTM, the progression rates, and resolution rates of MTM were evaluated.Results: A total of 120 eyes (120 patients) were included with an average follow-up of 15.4 months. During the follow-up, MTM progressed in 32 eyes (26.67%). The most common pattern of progression observed was the increased extent of retinoschisis in 12 eyes. The multivariate analysis showed that the presence of MTM progression had a significant correlation with internal limiting membrane (ILM) detachment and retinoschisis involved the entire macula at baseline. Five eyes (4.17%) experienced MTM resolution, of which 2 eyes developed disruptions of detached ILM, two eyes developed disruptions of epiretinal membrane, and one eye developed partial posterior vitreous detachment. Eyes with foveal detachment showed the highest progression rate (41.67%) and highest resolution rate (16.67%) compared to the eyes with other foveal complications.Conclusion: ILM detachment is a risk factor for MTM progression and MTM resolution can occur after ILM disruption. These suggest that ILM may play an important role as a biomarker in the evolution of MTM.

Selective and Inverse U-Shaped Curve Alteration of the Retinal Nerve in Amyotrophic Lateral Sclerosis: A Potential Mirror of the Disease

Introduction: Alterations in the visual pathway involving the retina have been reported in amyotrophic lateral sclerosis (ALS) but they lack consistency and subgroup analysis. We aimed to assess the retinal nerve fiber layer (RNFL) and retinal ganglion cells (RGCs) alterations in different stages of ALS patients and their association with ALS progression parameters.Methods: The study population consisted of 70 clinically diagnosed ALS patients and 55 age, sex matched controls. All of them underwent ophthalmic assessments and optical coherence tomography imaging. Four quadrants of the peripapillary RNFL and ganglion cell/inner plexiform complex (GCIP) were observed and automatically measured. Early-stage distal motor neuron axon dysfunction in ALS was detected by compound muscle action potential (CMAP) of the distal limbs within 12 months. The ALS disease parameters included the ALSFRS-R score and the disease progression rate (ΔFS).Results: Generally compared with controls, the nasal (p = 0.016) quadrant of the RNFL was thicker in ALS patients. When controlling for age and ΔFS, the RNFL(r = 0.37, p = 0.034) and GCIP(r = 0.40, p = 0.021) were significantly thickened as disease progressed within 12 months, while the RNFL declined with time after one year (r = −0.41, p = 0.037). ALS patients was subclassified into thickened RNFL (T-RNFL, &gt;95th percentile of normal), impaired RNFL (I-RNFL, &lt;5th percentile of normal) and normal RNFL. There were significant differences in the GCIP among the three groups (p &lt; 0.001). In the T-RNFL group (n = 18), the RNFL was negatively correlated with the abductor pollicis brevis-CMAP amplitude within 12 months (r = −0.56, p = 0.01). Patients within 12 months in this group progressed faster than others (p = 0.039). In the normal RNFL group (n = 22), 13 patients were diagnosed beyond 12 months, whose ΔFS was remarkably lower (p = 0.007). In I-RNFL group (n = 30), the early stage patients (&lt;12 months) had significant higher ΔFS (p = 0.006). One patient was with SOD1 pathogenic variant (p.A5V).Conclusion: Alterations of retinal nerve were not consistent in ALS patients with diverse phenotypes and progression rates. Generally speaking, the RNFL thickened during the first year and then gradually declined, which is related to but preceding the thickness change of the RGCs. Patients with a significant RNFL thinning in the early stage may have a faster progression rate. The inverse U-shaped curve transformation might be in accordance with early-stage motor neuron axonopathy.

Venous outflow profiles are associated with early edema progression in ischemic stroke

Background: In patients with acute ischemic stroke due to large vessel occlusion (AIS–LVO), development of extensive early ischemic brain edema is associated with poor functional outcomes, despite timely treatment. Robust cortical venous outflow (VO) profiles correlate with favorable tissue perfusion. We hypothesized that favorable VO profiles (VO+) correlate with a reduced early edema progression rate (EPR) and good functional outcomes. Methods: Multicenter, retrospective analysis to investigate AIS–LVO patients treated by mechanical thrombectomy between May 2013 and December 2020. Baseline computed tomography angiography (CTA) was used to determine VO using the cortical vein opacification score (COVES); VO+ was defined as COVES ⩾ 3 and unfavorable as COVES ⩽ 2. EPR was determined as the ratio of net water uptake (NWU) on baseline non-contrast CT and time from symptom onset to admission imaging. Multivariable regression analysis was performed to assess primary (EPR) and secondary outcome (good functional outcomes defined as 0–2 points on the modified Rankin scale). Results: A total of 728 patients were included. Primary outcome analysis showed VO+ (β: –0.03, SE: 0.009, p = 0.002), lower presentation National Institutes of Health Stroke Scale (NIHSS; β: 0.002, SE: 0.001, p = 0.002), and decreased time from onset to admission imaging (β: –0.00002, SE: 0.00004, p < 0.001) were independently associated with reduced EPR. VO+ also predicted good functional outcomes (odds ratio (OR): 5.07, 95% CI: 2.839–9.039, p < 0.001), while controlling for presentation NIHSS, time from onset to imaging, general vessel reperfusion, baseline Alberta Stroke Program Early CT Score, infarct core volume, EPR, and favorable arterial collaterals. Conclusions: Favorable VO profiles were associated with slower infarct edema progression and good long-term functional outcomes as well as better neurological status and ischemic brain alterations at admission.

Phylogenetic distribution of Ralstonia solanacearum species complex populations in potato in Kenya

Ralstonia solanacearum is a pathogen causing bacterial wilt disease of potato, resulting in 70% potato production losses in Kenya. A study was conducted to determine the diversity of Ralstonia solanacearum species complex strains within the main potato-growing regions of Kenya. Potato tubers were collected from different potato-growing regions of Kenya from visibly wilted potato plants, including tomato and irrigation water and cultured for pathogen isolation. Genomic DNA was isolated from 135 purified cultures of RSSC isolates and PCR amplified using multiplex and sequevar primers targeting the endoglucanase partial gene sequences. Pathogenicity test using R. solanacearum strain (phylotype II sequevar I) was done on Kenya Karibu, Shangi, Chulu, Wanjiku and Money Maker cultivars. Phylogenetic analysis of the partial endoglucanase gene identified two genospecies, R. pseudosolanacearum sp. nov (1.5%) and R. solanacearum (98.5%). All R. solanacearum strains clustered in sequevar I and were distributed in all the potato-growing regions surveyed. The cultivars were grown in a greenhouse for two cycles in a randomized complete block design and inoculated with R. solanacearum strain. The severity scores were assessed and the area under disease progress curve (AUDPC) was determined. All the cultivars tested for pathogenicity exhibited wilting symptoms at varying intervals after infection, with none showing complete resistance to R. solanacearum. Cultivar Shangi exhibited minimum disease severity and progression of 41.14% and AUDPC of 1041.7, respectively while Kenya Karibu was the most susceptible with a high progression rate of 68.24% and AUDPC of 1897.5, respectively. Money Maker, Chulu and Wanjiku showed no significant difference in disease severity depicting a simultaneous rate of infection among them. These findings provide valuable information to better understand the pathogen genetic diversity in Kenya and how it spreads.

Electromotive Drug Administration of Mitomycin C (EMDA/MMC) versus Intravesical Immunotherapy with Bacillus Calmette-Guérin (BCG) in Intermediate and High Risk Non Muscle Invasive Bladder Cancer

<b><i>Background:</i></b> Although TURB of tumor (TURBT) by itself can eradicate a non-muscle-invasive bladder cancer (NMIBC) completely, these tumors commonly recur and can progress to MIBC. It is, therefore, necessary to consider adjuvant therapy in most patients. The primary objective of the present study was to report our experience with EMDA/MMC and BCG, considering efficacy, progression, and recurrence, as adjuvant therapy in NMIBC patients; the secondary objective was to assess the efficacy of EMDA/MMC versus BCG as a comparative treatment. <b><i>Methods:</i></b> Between April 2016 and February 2020, a series of 216 patients, with a diagnosis of intermediate- and high-risk NMIBC after TURBT, underwent adjuvant intravesical therapy. In 26 cases with a failure of the treatment, in patients unfit and unwilling for radical cystectomy, a repeated intravesical therapy was performed (2 had a twice repetition). Out of 244 adjuvant therapies, 140 EMDA/MMC and 104 BCG treatments were done. The following data were collected for each patient: baseline demographics and clinical data and perioperative and postoperative data. Overall patients’ adjuvant intravesical therapies were included in a prospectively maintained institutional database, and a retrospective chart review was performed. We collected data on 2 main outcomes, recurrence-free survival (defined as a negative cystoscopy, cytology, and/or histology at the evaluation time point) and progression-free survival (defined as a negative cystoscopy or a nonprogressive tumor recurrence). <b><i>Results:</i></b> The NMIBC progression rate was higher in BCG than EMDA/MMC but not statistically significant (respectively, 4.2% vs. 2.5%; <i>p</i> = 0.703). In the overall population, the risk of NMIBC recurrence was higher after BCG than EMDA/MMC (<i>p</i> = 0.025). In the subgroups of 59 paired patients with similar characteristics, no difference was observed between groups in NMIBC progression and recurrence. <b><i>Conclusions:</i></b> Our findings suggest that EMDA/MMC and BCG are safe and reproducible approaches as adjuvant treatment in NMIBC. EMDA/MMC permits to achieve a fine oncological management as adjuvant treatment in NMIBC, which is not less than that obtained with BCG.

Bifurcation and Stabillity Analysis of HIV Transmission Model with Optimal Control

A mathematical model of HIV transmission is built and studied in this paper. The system’s equilibrium is calculated. A next-generation matrix is used to calculate the reproduction number. The novel method is used to examine the developed model’s bifurcation and equilibrium stability. The stability analysis result shows that the disease-free equilibrium is locally asymptotically stable if 0 < R 0 < 1 but unstable if R 0 > 1 . However, the endemic equilibrium is locally and globally asymptotically stable if R 0 > 1 and unstable otherwise. The sensitivity analysis shows that the most sensitive parameter that contributes to increasing of the reproduction number is the transmission rate β 2 of HIV transmission from HIV individuals to susceptible individuals and the parameter that contributes to the decreasing of the reproduction number is identified as progression rate η of HIV-infected individuals to AIDS individuals. Furthermore, it is observed that as we change η from 0.1 to 1 , the reproduction number value decreases from 1.205 to 1.189, where the constant value of β 2 = 0.1 . On the other hand, as we change the value of β 2 from 0.1 to 1 , the value of the reproduction number increases from 0.205 to 1.347, where the constant value of η = 0.1 . Further, the developed model is extended to the optimal control model of HIV/AIDS transmission, and the cost-effectiveness of the control strategy is analyzed. Pontraygin’s Maximum Principle (PMP) is applied in the construction of the Hamiltonian function. Moreover, the optimal system is solved using forward and backward Runge–Kutta fourth-order methods. The numerical simulation depicts the number of newly infected HIV individuals and the number of individuals at the AIDS stage reduced as a result of taking control measures. The cost-effectiveness study demonstrates that when combined and used, the preventative and treatment control measures are effective. MATLAB is used to run numerical simulations.

Substance Use-Related Cognitive Decline in Families with Autosomal Dominant Alzheimer’s Disease: A Cohort Study

Background: Cigarette smoking is a known risk factor for Alzheimer’s disease (AD). However, the association between neurodegeneration and other substances has not been fully determined. It is of vital importance to evaluate this relationship in populations at high risk of dementia. Since substance use possibly modifies the progression rate of cognitive decline, we studied this association in a unique and well-phenotyped cohort from the University of Antioquia: carriers of the PSEN1-E280A genetic variant. Objective: To determine the association between substance use and cognitive decline in carriers of the PSEN1-E280A genetic variant. Methods: A retrospective cohort study was conducted with 94 carriers and 69 noncarriers recruited between January 2019 and April 2020. A psychiatrist interviewed the participants using the Consumption of Alcohol, Cigarettes and other Substances questionnaire. The participants were also submitted to cognitive evaluation. The relationship between cognitive decline and substance use was explored through a mixed effects regression model. Results: There was an association between cigarettes and better performance on tasks related to perceptual organization, verbal fluency, and memory in carriers. Alcohol had a positive or negative effect on memory according to the type of alcoholic beverage. Results on marijuana use were no conclusive. Coffee was associated with progressive improvements in executive function and verbal fluency. Conclusion: Cigarette and alcohol were associated with an improvement of some cognitive assessments, possibly by a survival bias. In addition, coffee was related to improvements in executive function and language; therefore, its short-term neuroprotective potential should be studied.

Impact of acute kidney injury on long-term adverse outcomes in obstructive uropathy

Obstructive uropathy is known to be associated with acute kidney injury (AKI). This study aimed to investigate the etiologies, clinical characteristics, consequences and also assess the impact of AKI on long-term outcomes. This multicenter, retrospective study of 1683 patients with obstructive uropathy who underwent percutaneous nephrostomy (PCN) analyzed clinical characteristics, outcomes including progression to end-stage kidney disease (ESKD), overall mortality, and the impact of AKI on long-term outcomes. Obstructive uropathy in adults was most commonly caused by malignancy, urolithiasis, and other causes. AKI was present in 78% of the patients and was independently associated with preexisting chronic kidney disease (CKD). Short-term recovery was achieved in 56.78% after the relief of obstruction. ESKD progression rate was 4.4% in urolithiasis and 6.8% in other causes and older age, preexisting CKD, and stage 3 AKI were independent factors of progression. The mortality rate (34%) was highly attributed to malignant obstruction (52%) stage 3 AKI was also an independent predictor of mortality in non-malignant obstruction. AKI is a frequent complication of adult obstructive uropathy. AKI negatively affects long-term kidney outcomes and survival in non-malignant obstructions. A better understanding of the epidemiology and prognostic factors is needed for adult obstructive uropathy.

Inter-eye comparison of retinal vascular growth rate and angiographic findings following unilateral bevacizumab treatment

Purpose To compare retinal vascularization progression rate, final retinal vascularization, and fluorescein angiography (FA) findings in infants who received intravitreal bevacizumab (IVB) treatment in one eye and with spontaneous regression in the other eye. Methods Thirty eyes of 15 infants who underwent IVB in one eye due to asymmetric retinopathy of prematurity, and who had pre-treatment fundus photographs and fluorescein angiography images were included in the study. Horizontal disc diameter (DD), optic disc-to-fovea distance (FD), and the length of temporal retinal vascularization (LTRV) distance were measured by evaluating pre-treatment and FA images. Results The mean ages at the time of treatment and FA were 40.38 ± 3.35 and 68.72 ± 10.52 weeks postmenstrual age, respectively. The pre-treatment LTRV/FD ratio was 3.11 ± 0.41 in the treated eyes and 3.26 ± 0.43 in the non-treated eyes (p = 0.053). The final LTRV/FD ratio was 4.23 ± 0.38 in the treated group and 4.33 ± 0.37 in the non-treated group (p = 0.286). Staining of the vessels, hyperfluorescent focus, and irregular branching of the vessels were similar between the groups, respectively (p = 1.000; p = 0.250; p = 0.625). Conclusion The progression rate of retinal vascularization and angiographic findings were similar between the treated eyes and the non-treated eyes. Our study suggests that incomplete retinal vascularization in eyes treated with anti-vascular endothelial growth factor (VEGF) is due to the nature of the disease, and anti-VEGF treatment was not to cause cessation in vascular progression.