Signatures of cysteine oxidation on muscle structural and contractile proteins are associated with physical performance and muscle function in older adults: Study of Muscle, Mobility and Aging (SOMMA).

Oxidative stress is considered a contributor to declining muscle function and mobility during aging; however, the underlying molecular mechanisms remain poorly described. We hypothesized that greater levels of cysteine (Cys) oxidation on muscle proteins are associated with decreased measures of mobility. Herein, we applied a novel redox proteomics approach to measure reversible protein Cys oxidation in vastus lateralis muscle biopsies collected from 56 subjects in the Study of Muscle, Mobility and Aging (SOMMA), a community-based cohort study of individuals aged 70 years and older. We tested whether levels of Cys oxidation on key muscle proteins involved in muscle structure and contraction were associated with muscle function (leg power and strength), walking speed, and fitness (VO2 peak on cardiopulmonary exercise testing) using linear regression models adjusted for age, sex, and body weight. Higher oxidation levels of select nebulin Cys sites were associated with lower VO2 peak, while greater oxidation of myomesin-1, myomesin-2, and nebulin Cys sites was associated with slower walking speed. Higher oxidation of Cys sites in key proteins such as myomesin-2, alpha-actinin-2, and skeletal muscle alpha-actin were associated with lower leg power and strength. We also observed an unexpected correlation (R = 0.48) between a higher oxidation level of eight Cys sites in alpha-actinin-3 and stronger leg power. Despite this observation, the results generally support the hypothesis that Cys oxidation of muscle proteins impairs muscle power and strength, walking speed, and cardiopulmonary fitness with aging.

Accumulation of Large Ion Populations with High Ion Densities and Effects Due to Space Charge in Traveling Wave-Based Structures for Lossless Ion Manipulations (SLIM) IMS-MS.

The accumulation of very large ion populations in traveling wave (TW)-based Structures for Lossless ion Manipulations (SLIM) has been studied to better understand aspects of "in-SLIM" ion accumulation, and particularly its use in conjunction with ion mobility spectrometry (IMS). A linear SLIM ion path was implemented that had a "gate" for blocking and accumulating ions for arbitrary time periods. Removing the gate potential caused ions to exit, and the spatial distributions of accumulated ions examined. The ion populations for a set of peptides increased approximately linearly with increased accumulation times until space change effects became significant, after which the peptide precursor ion populations decreased due to growing space charge-related ion activation, reactions, and losses. Ion activation increased with added storage times and the TW amplitude. Lower amplitude TWs in the accumulation/storage region prevented or minimized ion losses or ion heating effects that can also lead to fragmentation. Our results supported the use of an accumulation region close to the SLIM entrance for speeding accumulation, minimizing ion heating, and avoiding ion population profiles that result in IMS peak tailing. Importantly, space charge-driven separations were observed for large populations of accumulated species and attributed to the opposing effects of space charge and the TW. In these separations, ion species form distributions or peaks, sometimes moving against the TW, and are ordered in the SLIM based on their mobilities. Only the highest mobility ions located closest to the gate in the trapped ion population (and where the highest ion densities were achieved) were significantly activated. The observed separations may offer utility for ion prefractionation of ions and increasing the dynamic range measurements, increasing the resolving power of IMS separations by decreasing peak widths for accumulated ion populations, and other purposes benefiting from separations of extremely large ion populations.

Evaluating Ion Accumulation and Storage in Traveling Wave Based Structures for Lossless Ion Manipulations.

Structures for lossless ion manipulations (SLIM) technology has demonstrated high resolving power ion mobility separation and flexibility to integrate complex ion manipulations into a single experimental platform. To enable IMS separations, trapping/accumulating ions inside SLIM (or in-SLIM) prior to injection of a packet for separations provides ease of operation and reduces the need for dedicated ion traps external to SLIM. To fully characterize the ion accumulation process, we have evaluated the effect of TW amplitudes, ion collection times, and storage times on the "in-SLIM" accumulation process. The study utilized a SLIM module comprising 5 distinct tracks, each with a specific ion accumulation configuration. The effect of the TW conditions on the accumulation process was investigated for a 3-peptide mixture: kemptide, angiotensin II, and neurotensin at a TW speed of 106 m/s. The effect of ion accumulation time/collection time and storage time was investigated, in addition to TW amplitude. Overall, the signal of the analyte ions increased when the ion collection time increased from 49 to 163 ms but decreased when the ion collection time increased further to 652 ms due to the space charge effects. Ion losses were observed at high TW amplitudes (e.g., 15 Vp-p and 20 Vp-p). In addition, under space charge conditions (e.g., collection times of 163 and 652 ms), the signal of the analyte ions decreased with an increase in storage times for all TW amplitudes applied to the trapping region. For ion accumulation, the data indicate that gentler TW conditions must be utilized to minimize ion losses and fragments to benefit from the "in-SLIM" accumulation process. Wider SLIM tracks provided better performance than those with narrower tracks.

Community knowledge, attitudes and practices related to Taenia solium taeniosis and cysticercosis in Zambia.

BACKGROUND: Several studies on Taenia solium taeniosis / cysticercosis (TSTC) have been conducted in Zambia. However, none has assessed community knowledge, attitudes and practices related to TSTC and epilepsy. METHODS: A community-based cross-sectional study was conducted between November and December 2022. The design consisted of a questionnaire-based survey conducted in each of the 25 purposely selected villages in Chiparamba Rural Health Centre (RHC) catchment area in Chipata district of the Eastern Province. RESULTS: A total of 588 participants comprising 259 (44%) males and 329 (56%) females with median age of 42 years (range 17 to 92 years) were interviewed. Awareness of the signs and symptoms of taeniosis and human cysticercosis (HCC), including transmission and prevention measures was very low. Whilst the majority had heard about epilepsy, they were not able to link HCC to epilepsy. Most participants were aware of cysticerci in pigs (PCC) including its predilection sites but were not aware of mode of transmission and prevention measures. The pork meat inspection by trained professionals was also not a common practice in the area. Risk perception of T. solium infections was thus very low. Overall knowledge, attitude and practice scores related to T. solium infections and to epilepsy were very low with median scores of 0.38 (IQR 0.25-0.54) for knowledge, 0.25 (0.25-0.50) for attitudes, and 0.31 (0.25-0.44) for practices. Males had better knowledge on TSTC (median = 0.42, p = 0.017, r = 0.098) and better practice scores (median = 0.38, p = < 0.001, r = 0.154) compared to females though the effect size was small. With regards to sanitation and hygiene washing with soap and water was reported by many but only few had a hand washing facility near their latrines. CONCLUSION: The study shows overall poor knowledge, attitudes and practices related to TSTC among the community of Chiparamba RHC in Chipata district of the Eastern Province of Zambia. This poses a serious challenge for control and elimination of T. solium infections and thus efforts to improve knowledge, attitudes and practices should be made using a One Health approach for the control and elimination of TSTC. Educational programs about TSTC transmission, signs and symptoms, prevention, management and control need to be scaled up in the study area and Zambia as a whole.

Effects of Alzheimer's disease and related dementias on dental care usage and economic burden in older adults: a cross-sectional study.

AIM: Distinct subtypes of Alzheimer's disease (AD) and related dementias (RD) might have different effects on dental care usage and economic burden. To determine the effects of AD and RD on specific types of dental care usage (preventive and treatment visits) and dental care costs from different payers (total and out-of-pocket costs). METHODS: A cross-sectional study was conducted using the Medicare Current Beneficiary Survey in 2016. This study identified 4268 community dwelling older adults with and without Alzheimer's disease and related dementias (ADRD) from a nationally representative sample of Medicare beneficiaries. Dental care usage and costs are based on self-reported data. Preventive dental events included preventive and diagnosis events. Treatment dental events included restorative, oral surgery and other events. RESULTS: This study identified 4268 (weighted N=30 423 885) older adults, including 94.48% without ADRD, 1.90% with AD and 3.63% with RD. Compared with older adults without ADRD, those with AD had similar dental care usage, but those with RD were 38% less likely to have treatment visit (OR: 0.62; 95% CI: 0.41 to 0.94) and had a 40% reduced number of total treatment visits (incidence rate ratio: 0.60; 95% CI: 0.37 to 0.98). RD was not associated with dental care costs, but AD was associated with higher total costs (ß: 1.08; 95% CI: 0.14 to 2.01) and higher out-of-pocket costs (ß: 1.25; 95% CI: 0.17 to 2.32). CONCLUSIONS: Patients with ADRD were more likely to have adverse dental care outcomes. Specifically, RD was associated with lower treatment dental care usage and AD was associated with higher total and out-of-pocket dental care costs. Effective patient-centred strategies should be used to improve dental care outcomes in patients with distinct subtypes of ADRD.

The epidemiology of human Taenia solium infections: A systematic review of the distribution in Eastern and Southern Africa.

BACKGROUND: Taenia solium is a tapeworm that causes taeniosis in humans and cysticercosis in humans and pigs. Within Eastern and Southern Africa (ESA), information on the presence of human taeniosis and cysticercosis seems scarce. This systematic review aimed to describe the current information available and gaps in the epidemiology of human T. solium infections in ESA. METHODS/PRINCIPLE FINDINGS: Scientific literature published between 1st January 2000 and 20th June 2022 in international databases [MEDLINE (Ovid), Embase (Ovid), Global Health (Ovid), Scopus (Elsevier), African Index Medicus (via WHO Global Index Medicus), and Open Grey] was systematically reviewed for ESA. The study area included 27 countries that make up the ESA region. Information on either taeniosis, cysticercosis or NCC was available for 16 of 27 countries within the region and a total of 113 reports were retained for the review. Most case reports for cysticercosis and NCC were from South Africa, while Tanzania had the most aggregated cysticercosis reports. Eleven countries reported on NCC with seven countries reporting data on NCC and epilepsy. Unconfirmed human T. solium taeniosis cases were reported in nine countries while two countries (Madagascar and Zambia) reported confirmed T. solium cases. The cysticercosis seroprevalence ranged between 0.7-40.8% on antigen (Ag) ELISA and between 13.1-45.3% on antibody (Ab) ELISA. Based on immunoblot tests the Ab seroprevalence was between 1.7-39.3%, while the proportion of NCC-suggestive lesions on brain CT scans was between 1.0-76% depending on the study population. The human taeniosis prevalence based on microscopy ranged between 0.1-14.7%. Based on Copro Ag-ELISA studies conducted in Kenya, Rwanda, Tanzania, and Zambia, the highest prevalence of 19.7% was reported in Kenya. CONCLUSIONS: Despite the public health and economic impact of T. solium in ESA, there are still large gaps in knowledge about the occurrence of the parasite, and the resulting One Health disease complex, and monitoring of T. solium taeniosis and cysticercosis is mostly not in place.

Six Year Extension Study of Patients From a Randomised Clinical Trial Comparing Venefit, Radiofrequency Induced Thermal Therapy, and Endovenous Radiofrequency Ablation for Treatment of Incompetent Great Saphenous Veins.

OBJECTIVE: To compare long term outcomes after great saphenous vein (GSV) treatment with three radiofrequency (RF) thermal devices: Venefit (Closurefast), Radiofrequency Induced Thermal Therapy (RFITT), and Endovenous Radiofrequency (EVRF). DESIGN: A 72 month follow up of patients who were treated in the randomised 3RF study. METHODS: A total of 172 participants from the 3RF study were invited to take part in a single visit, long term, follow up study. Failure of GSV closure was assessed with duplex ultrasound (DUS) and constituted the primary outcome. Patients completed questionnaires for secondary outcomes: Aberdeen Varicose Vein Questionnaire (AVVQ), Euroqol 5D (EQ-5D), and patient reported varicose veins measured by counting vein occupying boxes in AVVQ question 1. RESULTS: Twenty-two patients (12%) had already been re-treated. Of the remainder, 13 (7%) could not be contacted, 20 (11%) declined invitation, and one did not consent. Therefore, 116 (64%) and 95 (53%) participants completed questionnaires and DUS, respectively. Failure of GSV closure on 72 month DUS was 16%, 21%, and 37% for Venefit, RFITT, and EVRF, respectively (p = .14), whilst outcomes for all failures were 14%, 17%, and 44% (p < .001) (Venefit vs. EVRF: p < .001; RFITT vs. EVRF: p < .001; and Venefit vs. RFITT: p = .63). There were no between group differences in AVVQ or EQ-5D scores. Rates of patient reported presence of any varicose veins were high for all groups (97%, 92%, and 97% after Venefit, RFITT, and EVRF, respectively; p = .48). The EVRF treated participants reported more extensive recurrence than the Venefit and RFITT participants (p = .008). CONCLUSION: Long term technical outcomes after RF ablation for GSV varicose veins were significantly better after Venefit and RFITT compared with EVRF treatment. However, quality of life scores showed no differences after 72 months. Rates of patient reporting any varicose veins were high for all treatments. CLINICALTRIALS: gov Identifier: NCT04720027.

Multi-omics of NET formation and correlations with CNDP1, PSPB, and L-cystine levels in severe and mild COVID-19 infections.

The detailed mechanisms of COVID-19 infection pathology remain poorly understood. To improve our understanding of SARS-CoV-2 pathology, we performed a multi-omics and correlative analysis of an immunologically naïve SARS-CoV-2 clinical cohort from blood plasma of uninfected controls, mild, and severe infections. Consistent with previous observations, severe patient populations showed an elevation of pulmonary surfactant levels. Intriguingly, mild patients showed a statistically significant elevation in the carnosine dipeptidase modifying enzyme (CNDP1). Mild and severe patient populations showed a strong elevation in the metabolite L-cystine (oxidized form of the amino acid cysteine) and enzymes with roles in glutathione metabolism. Neutrophil extracellular traps (NETs) were observed in both mild and severe populations, and NET formation was higher in severe vs. mild samples. Our correlative analysis suggests a potential protective role for CNDP1 in suppressing PSPB release from the pulmonary space whereas NET formation correlates with increased PSPB levels and disease severity. In our discussion we put forward a possible model where NET formation drives pulmonary occlusions and CNDP1 promotes antioxidation, pleiotropic immune responses, and vasodilation by accelerating histamine synthesis.

Experimental animal models and their use in understanding cysticercosis: A systematic review.

BACKGROUND: Cysticercosis and Neurocysticercosis (NCC) can be studied using several animal species in experimental models which contributes to the understanding of the human form of the disease. Experimental infections of Taenia spp. are vital in explaining the modes of transmission of the parasite and helps the understanding of transmission of the parasite in humans and thus may be useful in designing therapeutic and immune-prophylactic studies to combat the disease. Thus, this systematic review aims to explore the existing experimental animal models to the understanding of cysticercosis in both humans and animals and elucidate the risk factors of cysticercosis and identify the Taenia spp. used in these models. METHODOLOGY: We systematically identified all publications from the Web of Science, Google Scholar, and Pubmed regarding experimental animal models using Taenia spp. that cause cysticercosis in both humans and animals. 58 studies were identified for eligibility. Of these, only 48 studies met the inclusion criteria from which data extraction was done and presented descriptively. RESULTS: Pigs, cattle, gerbils, mice, rats, voles, monkeys, cats, dogs, and goats were used in which T. solium, T. saginata, T. saginata asiatica, T. crassiceps and T. asiatica were studied. The routes used to induce disease were; oral, intravenous, subcutaneous, intramuscular, intraperitoneal, intraarterial, intracranial, intraduodenal, and surgical routes using eggs, oncospheres, and proglottids. Besides, the establishment of infection using eggs and oncospheres was affected by the route used to induce infection in the experimental animals. The cysticerci recovery rate in all the experimental studies was low and the number of animals used in these experiments varied from 1 to 84. Although not analysed statistically, sex, age, and breed of animals influenced the cysticerci recovery rate. Additionally, the cysticerci recovery rate and antibody-antigen levels were shown to increase with an increase in the dose of oncospheres and eggs inoculated in the animals. Contrasting results were reported in which the cysticerci recovery rate decreased with an increase in the dose of eggs inoculated. CONCLUSION: This review describes the various animal experiments using Taenia species that cause cysticercosis highlighting the animals used, age and their breed, the routes of infection used to induce disease and the sample size used, and the cysticerci recovery rate in these animal models.

Water-Assisted Proton Transfer in the Sequential Hydration of Benzonitrile Radical Cation C6H5CN•+(H2O)n: Transition to Hydrated Distonic Cation •C6H4CNH+(H2O)n with n ≥ 4.

The stepwise hydration of the benzonitrile•+ radical cation with one-seven H2O molecules was investigated experimentally and computationally with density functional theory in C6H5CN•+(H2O)n clusters. The stepwise binding energies (ΔHn-1,n°) were determined by equilibrium measurements for C6H5CN•+(H2O) and for •C6H4CNH+(H2O)n with n = 5, 6, and 7 to be 8.8 and 11.3, 11.0, and 10.0 kcal/mol, respectively. The populations of n = 2 and 3 of the C6H5CN•+(H2O)n clusters were observed only in trace abundance due to fast depletion processes leading to the formation of the hydrated distonic cations •C6H4CNH+(H2O)n with n = 4-7. The observed transition occurs between conventional radical cations hydrated on the ring in C6H5CN•+(H2O)n clusters with n = 1-3 and the protonated radical •C6H4CNH+ (distonic ion) formed by a proton transfer to the CN nitrogen and ionic hydrogen bonding to water molecules in •C6H4CNH+(H2O)n clusters with n = 4-7. The measured binding energy of the hydrated ion C6H5CN•+(H2O) (8.8 kcal/mol) is similar to that of the hydrated benzene radical cation (8.5 kcal/mol) that involves a relatively weak CHδ+···O hydrogen bonding interaction. Also, the measured binding energies of the •C6H4CNH+(H2O)n clusters with n = 5-7 are similar to those of the protonated benzonitrile (methanol)n clusters [C6H5CNH+(CH3OH)n, n = 5-7] that involve CNH+···O ionic hydrogen bonds. The proton shift from the para-•C ring carbon to the nitrogen of the benzonitrile radical cation is endothermic without solvent but thermoneutral for n = 1 and exothermic for n = 2-4 in C6H5CN•+(H2O)n clusters to form the distonic •C6H4CN···H+(OH2)n clusters. The distonic clusters •C6H4CN···H+(OH2)n constitute a new class of structures in radical ion/solvent clusters.

Effect of Traveling Waveform Profiles on Collision Cross Section Measurements in Structures for Lossless Ion Manipulations.

We evaluated the effect of four different waveform profiles (Square, Sine, Triangle, and asymmetric Sawtooth) on the accuracy of collision cross section (CCS) measurements using traveling wave ion mobility spectrometry (TWIMS) separations in structures for lossless ion manipulations (SLIM). The effects of the waveform profiles on the accuracy of the CCS measurements were evaluated for four classes of compounds (lipids, peptides, steroids, and nucleosides) at different TW speeds (126-206 m/s) and amplitudes (15-89 V). For the lipids and peptides, the TWIMS-based CCS (TWCCS) deviations from the corresponding drift-tube-based CCS (DTCCS) measurements were significantly lower in experiments conducted using the Sawtooth waveform compared to the square waveform. This observation can be rationalized by the lower maximum electric field experienced by ions with a Sawtooth waveform, as compared to the other waveforms, resulting in a lower probability for significant ion heating. We also observed that given approximately comparable resolution for all four waveforms, the Sawtooth waveform resulted in lower TWCCS error and a better agreement with DTCCS values than the Square waveform. In addition, for the steroids and nucleosides, an opposite TWCCS trend was observed, with higher errors with the Sawtooth waveform and lower with the Square waveform, suggesting that these molecules tend to become slightly more compact under ion heating conditions. Under optimum conditions, all TWCCS measurements on the SLIM platform were within 0.5% of those measured in the drift tube ion mobility spectrometry.

Challenges Encountered When Evaluating an Antibody-Detecting Point-of-Care Test for Taeniosis in an Endemic Community in Zambia: A Prospective Diagnostic Accuracy Study.

Taenia solium taeniosis diagnosis is challenging because current tests perform sub-optimally and/or are expensive, require sophisticated equipment, infrastructure and trained manpower, and therefore are not community deployable. A recently-developed, multi-strip, T. solium point-of-care test (TS POC) for simultaneous detection of tapeworm (TS POC T) and cysticercus (TS POC CC) human antibodies was evaluated for diagnostic accuracy on consecutively recruited community participants in Sinda district, Zambia. All participants were tested using the TS POC test. All test-positives and 20% of the test-negative participants were invited to give a blood and stool sample for reference testing. Three different reference tests were used for taeniosis diagnosis: recombinant rES33 enzyme-linked immunoelectrotransfer blot (rES33 EITB), copro PCR and copro Ag ELISA. Bayesian analysis with probabilistic constraints was used to estimate sensitivity and specificity. In total, 1254 participants were tested with the TS POC test, of whom 13 tested positive using the TS POC T. Based on 161 participants with complete data, the estimated sensitivity and specificity for the TS POC T test were 38% (95% CI: 5-93%) and 99% (95% CI: 98-100%), respectively. The challenge of highly variable inter-assay performance is highlighted. We recommend either increasing the sensitivity or redesigning the test.

Evaluation of an Antibody Detecting Point of Care Test for Diagnosis of Taenia solium Cysticercosis in a Zambian Rural Community: A Prospective Diagnostic Accuracy Study.

The lack of cheap, easy-to-use, rapid diagnostic tests has led to the development of several rapid diagnostic tests for cysticercosis. The new prototype two-strip, Taenia solium point of care test (TS POC) detects antibodies against taeniosis (TS POC T) and cysticercosis (TS POC CC). This study evaluated the diagnostic performance of the TS POC CC in the Sinda district in eastern Zambia. A sample of 1254 participants was recruited and tested with the TS POC. Out of the 1249 participants with a valid TS POC result, 177 (14%) tested positive while 1072 (86%) tested negative. All individuals with a positive TS POC and a subset of negative TS POC participants were selected for serum sampling, and were subjected to the recombinant glycoprotein T24H enzyme-linked immunoelectrotransfer blot (rT24H EITB) and the serum B60/158 (serum Ag) enzyme-linked immunosorbent assay (Ag ELISA). Performance characteristics were estimated using a Bayesian approach with probabilistic constraints. Based on 255 complete cases, the estimated sensitivity and specificity of the TS POC CC test were 35% (95% CI: 14-63%) and 87% (95% CI: 83-90%), respectively. The diagnostic performance needs to be improved, possibly by titrating antigen and other reagents' concentration in the strip to produce a performance similar to existing cysticercosis tests such as the rT24H EITB.

Trial Design for a Diagnostic Accuracy Study of a Point-of-Care Test for the Detection of Taenia solium Taeniosis and (Neuro)Cysticercosis in Community Settings of Highly Endemic, Resource-Poor Areas in Zambia: Challenges and Rationale.

Field-applicable, high-quality, and low-cost diagnostic tools are urgently needed for Taenia solium. The aim of this paper is to describe the design, challenges, and rationale for the design of a diagnostic accuracy study in low-resource community settings in Zambia. The trial was designed as a prospective study with a two-stage design to evaluate a new point-of-care test (TS POC) for the detection of taeniosis and (neuro)cysticercosis. Participants within randomly selected households were tested with the TS POC test (index test). Participants who tested TS POC positive for taeniosis and/or cysticercosis and a subset of the negatives were requested to give blood and stool samples for reference testing, and to undergo clinical examination and a cerebral CT scan. The difficulties of conducting a clinical trial in settings with limited research and neuroimaging infrastructure as well as peculiarities specifically related to the disease (low prevalence of taeniosis and the lack of a gold standard) were taken into consideration for the design of this study. The two-stage design increased the efficiency of the study by reducing the number of samples, clinical examinations, and CT scans. Simplified flows and sampling processes were preferred over complex follow-up and randomization systems, aiming to reduce bias and increase the generalizability of the study.

p16-3MR: A Novel Model to Study Cellular Senescence in Cigarette Smoke-Induced Lung Injuries.

Cellular senescence and lung aging are associated with the pathogenesis of chronic obstructive pulmonary disease (COPD). COPD progresses with aging, and chronic smoking is the key susceptibility factor in lung pathological changes concurrent with mitochondrial dysfunction and biological aging. However, these processes involving cigarette smoke (CS)-mediated lung cellular senescence are difficult to distinguish. One of the impediments to studying cellular senescence in relation to age-related lung pathologies is the lack of a suitable in vivo model. In view of this, we provide evidence that supports the suitability of p16-3MR mice to studying cellular senescence in CS-mediated and age-related lung pathologies. p16-3MR mice have a trimodal reporter fused to the promoter of the p16INK4a gene that enables detection, isolation, and selective elimination of senescent cells, thus making them a suitable model to study cellular senescence. To determine their suitability in CS-mediated lung pathologies, we exposed young (12-14 months) and old (17-20 months) p16-3MR mice to 30 day CS exposure and studied the expression of senescent genes (p16, p21, and p53) and SASP-associated markers (MMP9, MMP12, PAI-1, and FN-1) in air- and CS-exposed mouse lungs. Our results showed that this model could detect cellular senescence using luminescence and isolate cells undergoing senescence with the help of tissue fluorescence in CS-exposed young and old mice. Our results from the expression of senescence markers and SASP-associated genes in CS-exposed young and old p16-3MR mice were comparable with increased lung cellular senescence and SASP in COPD. We further showed alteration in the; (i) tissue luminescence and fluorescence, (ii) mRNA and protein expressions of senescent markers and SASP genes, and (iii) SA-ß-gal activity in CS-exposed young and old p16-3MR mice as compared to their air controls. Overall, we showed that p16-3MR is a competent model for studying the cellular senescence in CS-induced pathologies. Hence, the p16-3MR reporter mouse model may be used as a novel tool for understanding the pathobiology of cellular senescence and other underlying mechanisms involved in COPD and fibrosis.

Operational characteristics of an antibody detecting point of care test for Taenia solium infections in a community and hospital setting.

BACKGROUND: Diagnostic test evaluation includes measures of performance and assessment of operational characteristics. The latter focuses on end-user understanding of instructions to perform the test, ease of use, test turnaround time and ease of result interpretation. This study aimed to assess user comprehension of training for and ease of use of a Taenia solium point of care test (TS POC) evaluated in a community and hospital setting in Zambia and Tanzania, respectively. METHODS: The TS POC is a three-step in-house-produced rapid diagnostic test (RDT) for the simultaneous detection of taeniosis (TST) and cysticercosis (TSCC) antibodies. Data collected by administering questionnaires to 29 end-users and from the main evaluation database was analyzed quantitatively. RESULTS: End-users (28/29, 97%) perceived that the training they received for performing the test was sufficient. They performed 4080 tests, of which 80 were invalid. The community-based study and TST tests had higher invalid rates. The overall result interpretation was within the acceptable range of RDTs with an overall disagreement between readers of 3.3%. The Kappa coefficient of agreement was 85 and 82% for TSCC and TST, respectively. There was more disagreement among readers in the community-based study. CONCLUSION: End-users rated the TS POC kit moderate in terms of ease of use citing long test turnaround time and difficulties in using the blood transfer device. Overall, the operational performance of the TS POC kit and end-users was within the established acceptable performance range.