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Testing for mycobacterial lipoarabinomannan (LAM) in urine is a practical but insensitive alternative to sputum testing to diagnose tuberculosis (TB) in people with HIV (PWH). Here, we evaluated urine LAM testing alongside PCR-based tests for Mycobacterium tuberculosis (MTB) DNA in tongue swabs. We hypothesized that the two nonsputum samples would deliver complementary, not redundant, results. The study included 131 South African patients of whom 64 (48.1%) were confirmed to have TB by GeneXpert MTB/RIF Ultra (Xpert Ultra) or culture analysis of sputum. A total of 120 patients (91.6%) were coinfected with HIV and 130 yielded a valid urine LAM result (Alere DETERMINE LAM Ag). Tongue swab samples were tested by IS6110-targeted qPCR with a quantification cycle (Cq) cutoff of 32. Relative to reference sputum testing (TB culture and Xpert Ultra), combined urine LAM and oral swab testing (either sample positive) was significantly more sensitive than either nonsputum sample alone (57% sensitivity for combined testing versus 35% and 39% sensitivity for urine LAM and tongue swabs; P = 0.01 and 0.04, respectively). Specificity of combined testing (neither sample positive) was 97%. On average, tongue swab-positive participants had higher sputum signal strength than urine-LAM positive participants, as measured by sputum Xpert Ultra Cq value (P = 0.037). A subset of tongue swabs (N = 18) was also tested by using Xpert Ultra, which reproduced true positive and true negative IS6110 qPCR results and resolved the two false-positive tongue swabs. With further development, tongue swabs and urine may feasibly serve as complementary nonsputum samples for diagnosis of TB in PWH.

Patient-Collected Swabs for SARS-CoV-2 Testing Tongue, nasal, and mid-turbinate swabs to detect SARS-CoV-2 were collected by 530 outpatients before a health care worker collected nasopharyngeal swa...

Oral swab analysis (OSA) has been shown to detectMycobacterium tuberculosis(MTB) DNA in patients with pulmonary tuberculosis (TB). In previous analyses, qPCR testing of swab samples collected from tongue dorsa was up to 93% sensitive relative to sputum GeneXpert, when 2 swabs per patient were tested. The present study modified sample collection methods to increase sample biomass and characterized the viability of bacilli present in tongue swabs. A qPCR targeting conserved bacterial ribosomal rRNA gene (rDNA) sequences was used to quantify bacterial biomass in samples. There was no detectable reduction in total bacterial rDNA signal over the course of 10 rapidly repeated tongue samplings, indicating that swabs collect only a small portion of the biomass available for testing. Copan FLOQSwabs collected ~2-fold more biomass than Puritan PurFlock swabs, the best brand used previously (p = 0.006). FLOQSwabs were therefore evaluated in patients with possible TB in Uganda. A FLOQSwab was collected from each patient upon enrollment (Day 1) and, in a subset of sputum GeneXpert Ultra-positive patients, a second swab was collected on the following day (Day 2). Swabs were tested for MTB DNA by manual IS6110-targeted qPCR. Relative to sputum GeneXpert Ultra, single-swab sensitivity was 88% (44/50) on Day 1 and 94.4% (17/18) on Day 2. Specificity was 79.2% (42/53). Among an expanded sample of Ugandan patients, 62% (87/141) had colony-forming bacilli in their tongue dorsum swab samples. These findings will help guide further development of this promising TB screening method.

Oral swabs are emerging as a non-invasive sample type for diagnosing infectious diseases including Ebola, tuberculosis (TB), and COVID-19. To assure proper sample collection, sample adequacy controls (SACs) are needed that detect substances indicative of samples collected within the oral cavity. This study evaluated two candidate SACs for this purpose. One detected representative oral microbiota (Streptococcus species DNA) and the other, human cells (human mitochondrial DNA, mtDNA). Quantitative PCR (qPCR) assays for the two target cell types were applied to buccal swabs (representing samples collected within the oral cavity) and hand swabs (representing improperly collected samples) obtained from 51 healthy U.S. volunteers. Quantification cycle (Cq) cutoffs that maximized Youden’s index were established for each assay. The streptococcal target at a Cq cutoff of ≤34.9 had 99.0% sensitivity and specificity for oral swab samples, whereas human mtDNA perfectly distinguished between hand and mouth swabs with a Cq cutoff of 31.3. The human mtDNA test was then applied to buccal, tongue, and gum swabs that had previously been collected from TB patients and controls in South Africa, along with “air swabs” collected as negative controls (total N = 292 swabs from 71 subjects). Of these swabs, 287/292 (98%) exhibited the expected Cq values. In a paired analysis the three oral sites yielded indistinguishable amounts of human mtDNA, however PurFlock™ swabs collected slightly more human mtDNA than did OmniSwabs™ (p = 0.012). The results indicate that quantification of human mtDNA cannot distinguish swabs collected from different sites within the mouth. However, it can reliably distinguish oral swabs from swabs that were not used orally., which makes it a useful SAC for oral swab-based diagnosis.

In schizophrenia patients, one of the most commonly studied deficits of social cognition is emotion processing (EP), which has documented links to facial recognition (FR). But, how are deficits in facial recognition linked to emotion processing deficits? Can neurocognitive and symptom correlates of FR and EP help differentiate the unique contribution of FR to the domain of social cognition?A meta-analysis of 102 studies (combined n=4826) in schizophrenia patients was conducted to determine the magnitude and pattern of relationships between facial recognition, emotion processing, neurocognition, and type of symptom.Meta-analytic results indicated that facial recognition and emotion processing are strongly interrelated (r=.51). In addition, the relationship between FR and EP through voice prosody (r=.58) is as strong as the relationship between FR and EP based on facial stimuli (r=.53). Further, the relationship between emotion recognition, neurocognition, and symptoms is independent of the emotion processing modality - facial stimuli and voice prosody.The association between FR and EP that occurs through voice prosody suggests that FR is a fundamental cognitive process. The observed links between FR and EP might be due to bottom-up associations between neurocognition and EP, and not simply because most emotion recognition tasks use visual facial stimuli. In addition, links with symptoms, especially negative symptoms and disorganization, suggest possible symptom mechanisms that contribute to FR and EP deficits.

To obtain Food and Drug Administration approval for the treatment of cognitive impairments associated with schizophrenia, a drug will need to demonstrate benefits beyond those that may be documented on objective cognitive tests. Interview-based measures of cognition such as the Cognitive Assessment Interview (CAI) are candidate coprimary outcome measures.Psychiatrically stable schizophrenia outpatients (n=150) were studied using the CAI to obtain information about cognitive functioning from both the patient and an informant. Patients also received objective assessments of neurocognition, functional capacity, functional outcome, and symptoms, at baseline and 1 month later.The CAI had good internal consistency (Cronbach's alpha=.92) and good test-retest reliability (r=.83). The CAI was moderately correlated with objective neurocognitive test scores (r's=-.39 to -.41) and moderately correlated with social functioning (r=-.38), work functioning (r=-.48), and overall functional outcome (r=-.49). The correlations of CAI scores with external validity indicators did not differ significantly by source of information (patient alone ratings were valid). Overall functional outcome correlated more strongly with patient CAI scores (r=-.50) than with objective neurocognitive test scores (r=.29) or functional capacity (r=.29).Field testing of the CAI produced reliable ratings of cognitive functioning that were correlated with functional outcome. Patient ratings alone yielded scores with reliability and validity values appropriate for use in clinical trials. The CAI appears to provide useful complementary information and possesses practical advantages for rating cognitive functioning including an interview-based method of administration, brief assessment time (15 min for the patient assessment), little or no practice effects, and ease of scoring.

Background Although in the early course of schizophrenia relapse prevention is of paramount importance, there is an increasing emphasis on establishing and maintaining sustained periods of symptom remission. Recovery in the early course of illness is also possible, although the rates of recovery are lower than for symptom remission. Symptom remission and recovery rates vary considerably across recent-onset schizophrenia studies because of a lack of consistency in treatment interventions and in applying operational outcome criteria. Method Patients who were within two years of their first psychotic episode (N = 77) that were treated with continuous antipsychotic medication in conjunction with psychosocial interventions (without targeted work rehabilitation) were assessed during the first outpatient year after hospital discharge. Published operational criteria were used to classify symptom remission and recovery. Results The rate of full symptom remission maintained for 6 months was 36%, while the rate of recovery for 6 months was 10%. When the same criteria were applied for a continuous period of one year, 22% of patients were found to achieve symptom remission but only 1% of patients met recovery criteria. Using multivariate prediction, the WAIS Comprehension score was a significant predictor of 6 months of good functional outcome. Conclusions Although some schizophrenia patients can achieve both symptom remission and recovery in the early course of illness, the overall rate of symptom remission during the first post-hospitalization year is much higher than the rate of recovery. This suggests that interventions targeting work and social functioning are likely necessary to raise the chances of recovery. Cognitive factors can be predictive of good functional outcome even in the early course of schizophrenia.

Background: The existence of deficits in several social cognitive domains has been established in schizophrenia, and those impairments are known to be a significant determinant of functional outcome. Both symptoms and neurocognition have been linked to social cognitive deficits, but the nature and the relative strength of these relationships have not been established. Methods: A meta-analysis of 154 studies (combined N = 7175) was conducted to determine the magnitude of the relationships between 3 symptom domains (reality distortion, disorganization, and negative symptoms) and 6 Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) domains of neurocognition with 4 domains of social cognition. Analyses were conducted to determine whether the strength of these relationships differed depending on the symptom type or neurocognitive domain under investigation. Results: The correlations between reality distortion and the domains of social cognition ranged from near zero to moderate (r’s range from −.07 to −.22), as compared with the moderate association for disorganization (r’s range from −.22 to −.32) and negative symptoms (r’s range from −.20 to −.26). For each of the neurocognitive domains, the relationships to social cognitive domains were mostly moderate (r’s range from .17 to .37), with no one neurocognitive domain being prominent. Conclusions: The effect sizes of the correlations between disorganization and negative symptoms with social cognition were relatively larger and more consistent than reality distortion. The relationship between social cognition and 6 MATRICS domains of neurocognition were mostly moderate and relatively consistent. When considering disorganization and negative symptoms, the relationship to social cognitive processes was relatively as strong as for neurocognition.

Climate change poses multiple risks to the population of Lima, the largest city and capital of Peru, located on the Pacific coast in a desert ecosystem. These risks include increased water scarcity, increased heat, and the introduction and emergence of vector-borne and other climate sensitive diseases. To respond to these threats, it is necessary for the government, at every level, to adopt more mitigation and adaptation strategies. Here, focus groups were conducted with representatives from five Lima municipalities to determine priorities, perception of climate change, and decision-making processes for implementing projects within each municipality. These factors can affect the ability and desire of a community to implement climate change adaptation and mitigation strategies. The results show that climate change and other environmental factors are of relatively low priority, whereas public safety and water and sanitation services are of highest concern. Perhaps most importantly, climate change is not well understood among the municipalities. Participants had trouble distinguishing climate change from other environmental issues and did not fully understand its causes and effects. Greater understanding of what climate change is and why it is important is necessary for it to become a priority for the municipalities. Different aspects of increased climate change awareness seem to be connected to having experienced extreme weather events, whether related or not to climate change, and to higher socioeconomic status.

Diagnosis of pulmonary tuberculosis (TB) usually includes laboratory analysis of sputum, a viscous material derived from deep in the airways of patients with active disease. As a diagnostic sample matrix, sputum can be difficult to collect and analyze by microbiological and molecular techniques. An alternative, less invasive sample matrix could greatly simplify TB diagnosis. We hypothesized that Mycobacterium tuberculosis cells or DNA accumulate on the oral epithelia of pulmonary TB patients and can be collected and detected by using oral (buccal) swabs. To test this hypothesis, 3 swabs each were collected from 20 subjects with active pulmonary TB and from 20 healthy controls. Samples were tested by using a polymerase chain reaction (PCR) specific to the M. tuberculosis IS6110 insertion element. Eighteen out of 20 confirmed case subjects (90%) yielded at least 2 positive swabs. Healthy control samples were 100% negative. This case-control study supports past reports of M. tuberculosis DNA detection in oral swabs. Oral swab samples are non-invasive, non-viscous and easy to collect with or without active TB symptoms. These characteristics may enable simpler and more active TB case finding strategies.

Factor analytic studies have shown that in schizophrenia patients, disorganization (e.g., conceptual disorganization and bizarre behavior) is a separate dimension from other types of positive symptoms such as reality distortion (delusions and hallucinations). Although some studies have found that disorganization is more strongly linked to neurocognitive deficits and poor functional outcomes than reality distortion, the findings are not always consistent.A meta-analysis of 104 studies (combined n=8015) was conducted to determine the magnitude of the relationship between neurocognition and disorganization as compared to reality distortion. Additional analyses were conducted to determine whether the strength of these relationships differed depending on the neurocognitive domain under investigation.The relationship between reality distortion and neurocognition was weak (r=-.04; p=.03) as compared to the moderate association between disorganization and neurocognition (r=-.23; p.01). In each of the six neurocognitive domains that were examined, disorganization was more strongly related to neurocognition (r's range from -.20 to -.26) than to reality distortion (r's range from .01 to -.12).The effect size of the relationship between neurocognition and disorganization was significantly larger than the effect size of the relationship between neurocognition and reality distortion. These results hold across several neurocognitive domains. These findings support a dimensional view of positive symptoms distinguishing disorganization from reality distortion.