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Background: Patients with TB resistant to rifampicin (Rr-TB), and those with additional resistance to fluoroquinolones (pre-XDR-TB), should be treated with bedaquiline-pretomanid-linezolid-moxifloxacin and bedaquiline-pretomanid-linezolid, respectively. However, pretomanid is not yet widely available., Methods: This is a pragmatic prospective single-arm study investigating the efficacy and safety of 9 mo of bedaquiline-delamanid-linezolid-clofazimine in patients with pre-XDR-TB or Rr-TB unresponsive to Rr-TB treatment in Nigeria., Results: From January 2020 to June 2022, 14 of 20 patients (70%) successfully completed treatment, five died and one was lost-to-follow-up. No one experienced a treatment-emergent grade three/four event. Treatment success was higher compared with global pre-XDR-TB treatment outcomes., Conclusions: While pretomanid is unavailable, highly resistant TB can be treated with bedaquiline-delamanid-linezolid-clofazimine., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Objective:: To use baseline audiogram parameters in order to ascertain whether drug-resistant tuberculosis (DR-TB) has effects on hearing, as well as to describe the configurations of the audiograms and to determine whether there are parameters that can be associated with those configurations., Methods:: This was a prospective study involving patients diagnosed with DR-TB at a tuberculosis treatment center in the state of Ogun, in Nigeria. The patients included in the study were submitted to pure tone audiometry at baseline (within two weeks after treatment initiation). For comparative analyses, data regarding demographic and clinical characteristics were collected from the medical records of the patients., Results:: The final sample comprised 132 patients. The mean age of the patients was 34.5 ± 12.6 years (range, 8-82 years), and the male:female ratio was 2:1. Of the 132 patients, 103 (78.0%) resided in neighboring states, 125 (94.7%) had previously experienced antituberculosis treatment failure, and 18 (13.6%) were retroviral-positive. Normal audiograms were found in 12 patients (9.1%), whereas sensorineural hearing loss was identified in 104 (78.8%), the two most common configurations being ascending, in 54 (40.9%), and sloping, in 26 (19.7%). Pure-tone averages at low frequencies (0.25-1.0 kHz) and high frequencies (2.0-8.0 kHz) were 33.0 dB and 40.0 dB, respectively. Regarding the degree of hearing loss in the better ear, 36 patients (27.3%) were classified as having normal hearing and 67 (50.8%) were classified as having mild hearing loss (26-40 dB), whereas 29 (21.9%) showed moderate or severe hearing loss. Among the variables studied (age, gender, retroviral status, previous treatment outcome, and weight at admission), only male gender was associated with audiometric configurations., Conclusions:: In this sample of patients with DR-TB, most presented with bilateral, mild, suboptimal sensorineural hearing loss, and ascending/sloping audiometric configurations were associated with male gender., Objetivo:: Utilizar parâmetros do audiograma basal para verificar se a tuberculose resistente (TB-R) tem efeitos na audição, descrever as configurações dos audiogramas e determinar se há parâmetros que possam ser associados a essas configurações., Métodos:: Estudo prospectivo com pacientes diagnosticados com TB-R em um centro de tratamento de tuberculose no estado de Ogun, Nigéria. Os pacientes incluídos no estudo foram submetidos à audiometria de tons puros em até duas semanas após o início do tratamento (audiometria basal). Características demográficas e clínicas foram coletadas dos prontuários médicos dos pacientes para análises comparativas., Resultados:: A amostra final envolveu 132 pacientes. A média de idade dos pacientes foi de 34,5 ± 12,6 anos (variação, 8-82 anos), e a razão homem:mulher foi de 2:1. A maioria dos pacientes (n = 103; 78,0%) residia nos estados vizinhos e tinha história de falha de tratamento antituberculose (n = 125; 94.7%); 18 (13.6%) apresentavam status retroviral positivo. Doze pacientes (9,1%) apresentaram audiogramas normais, e 104 (78,8%) apresentaram perda auditiva neurossensorial, sendo as configurações mais comuns do tipo ascendente, em 54 (40,9%), e descendente, em 26 (19,7%). As médias de tons puros em frequências baixas (0,25-1,0 kHz) e altas (2,0-8,0 kHz) foram de 33,0 dB e 40,0 dB, respectivamente. Quanto ao grau de perda auditiva no melhor ouvido, 36 pacientes (27,3%) apresentaram audição normal, e 67 (50,8%) apresentaram perda auditiva leve (26-40 dB), enquanto 29 (21,9%) mostraram perda auditiva moderada ou grave. Entre as variáveis estudadas (idade, gênero, status retroviral, desfecho de tratamento anterior e peso na admissão), somente o gênero masculino foi associado às configurações audiométricas., Conclusões:: Nesta amostra de pacientes com TB-R, a maioria apresentou perda auditiva neurossensorial leve e subótima bilateralmente, com configurações audiométricas ascendentes/descendentes associadas ao gênero masculino.

The impact of asthma, exposure period, and filter condition downstream of the mixing box of air-conditioning system on building occupants' perceptual response, work performance, and salivary α-amylase secretion during exposures to ozone and its initiated chemistry products is studied. The experiments were conducted in a field environmental chamber (FEC) (240 m(3)) simulating an office environment. Experiments were conducted during periods when the air-handling system operated with new or used pleated panel filters at constant recirculation (7/h) and ventilation (1/h) rates. Average ozone and secondary organic aerosols (ozone-initiated chemistry products) measured during non-asthmatic and asthmatic subjects' 3-h exposures in the FEC were in the ranges approximately 20-37 ppb and approximately 1.6-3 μg/m(3), respectively. Asthmatic subjects' perceived odor intensity and sensory (eye, nose, and throat) irritation ratings were generally lower than those of non-asthmatic subjects, possibly explaining why asthmatic subjects accept perceived air quality more than non-asthmatic subjects. However, asthmatic subjects' perceived physiological-like symptom ratings (flu, chest tightness, and headache) and concentrations of secreted salivary α-amylase were generally higher than those of non-asthmatic subjects. Asthmatic subjects had significantly lower accuracy than non-asthmatic subjects in a task that required higher concentration although they had higher work speed. Filter condition did not make any significant difference for subjects' responses., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Several studies have documented reductions in indoor ozone levels that occur as a consequence of its reactions with the exposed skin, hair and clothing of human occupants. One would anticipate that consumption of ozone via such reactions would impact co-occurring products derived from ozone's reactions with various indoor pollutants. The present study examines this possibility for secondary organic aerosols (SOA) derived from ozone-initiated chemistry with limonene, a commonly occurring indoor terpene. The experiments were conducted at realistic ozone and limonene concentrations in a 240 m(3) chamber configured to simulate a typical open office environment. During an experiment the chamber was either unoccupied or occupied with 18-20 workers. Ozone and particle levels were continuously monitored using a UV photometric ozone analyzer and a fast mobility particle sizer (FMPS), respectively. Under otherwise identical conditions, when workers were present in the simulated office the ozone concentrations were approximately two-thirds and the SOA mass concentrations were approximately one-half of those measured when the office was unoccupied. This was observed whether new or used filters were present in the air handling system. These results illustrate the importance of accounting for occupancy when estimating human exposure to pollutants in various indoor settings.

A series of phosphorus compounds, designed as analogues of gamma-aminobutyric acid (GABA) in that they possess a P = O moiety separated by three atoms from an amino or acetamido group, was synthesized and tested by using in vitro GABAA and GABAB receptor binding, GABA uptake assays, and was examined for anticonvulsant activity. Weak GABAB receptor affinity was noted for one agent, whereas six compounds displayed moderate to high potencies as inhibitors of electroshock- and pentylenetetrazol-induced seizures. The best anticonvulsant effect was found with the (m-aminophenyl) phosphinic acid compounds, with members of this class selected for further study.