Search

Postoperative infections are the most common complications faced by surgeons after implant surgery. To address this issue, an emerging and promising approach is to develop antimicrobial coatings using antibiotic substitutes. We investigated the use of polycationic homopolypeptides in a layer-by-layer coating combined with hyaluronic acid (HA) to produce an effective antimicrobial shield. The three peptide-based polycations used to make the coatings, poly(l-arginine) (PAR), poly(l-lysine), and poly(l-ornithine), provided an efficient antibacterial barrier by a contact-killing mechanism against Gram-positive, Gram-negative, and antibiotic-resistant bacteria. Moreover, this activity was higher for homopolypeptides containing 30 amino-acid residues per polycation chain, emphasizing the impact of the polycation chain length and its mobility in the coatings to deploy its contact-killing antimicrobial properties. However, the PAR-containing coating emerged as the best candidate among the three selected polycations, as it promoted cell adhesion and epithelial monolayer formation. It also stimulated nitric oxide production in endothelial cells, thereby facilitating angiogenesis and subsequent tissue regeneration. More interestingly, bacteria did not develop a resistance to PAR and (PAR/HA) also inhibited the proliferation of eukaryotic pathogens, such as yeasts. Furthermore, in vivo investigations on a (PAR/HA)-coated hernia mesh implanted on a rabbit model confirmed that the coating had antibacterial properties without causing chronic inflammation. These impressive synergistic activities highlight the strong potential of PAR/HA coatings as a key tool in combating bacteria, including those resistant to conventional antibiotics and associated to medical devices.

This work presents a rad-hard 12-bit 3 MS/s resistor string DAC for space applications. The converter has been developed using rad-hardened techniques both at architecture and layout levels starting from a conventional topology. The design considers the different effects of the radiation that could damage the circuits in space environments. The DAC has been developed and integrated a standard CMOS 0.13 μm technology by IHP, using RHBD techniques. Low Earth Orbit (LEO) requires a TID value of around 100 krad (Si), according to the expected length of the mission. The temperature range is between −55 °C and 125 °C. The DAC power budget is similar to that of terrestrial applications. The measured INL (Integral Non-Linearity) and DNL (Differential Non-Linearity) are better than 0.2 LSB, while the ENOB (Effective Number Of Bits) at a 3 MS/s clock exceeds 9.7 bits while loading a 10 pF capacitor. The DAC has been characterized under radiation, showing a fluctuation in the analog output lower than 2 LSB (mainly due to measurement uncertainty) up to 500 krad (Si). Power consumption shows a negligible increase, too. A 10-bit version of the same DAC as the downscaled 12-bit one has been developed as well.

Objectives To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it.Methods Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018–2023). Maternal and infant information were collected in a web-based database.Results We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress.Conclusions Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.

Background. Heart transplantation in South Africa faces numerous challenges related to organ scarcity and unequal access to advanced heart therapy. There is an urgent need to analyse the current transplant referral pathway to optimise equitable access to transplantation. Objectives. To provide an audit of heart transplant referrals to Groote Schuur Hospital, Cape Town, over a 23-year period, focusing on patient demographics, indications for referral, waiting-list dynamics, and transplant referral outcomes. Methods. The study utilised a retrospective patient folder review for the period 1 January 1997 - 31 December 2019 and audited the trends in heart transplant referrals and associated outcomes of the referral at a tertiary academic hospital. Results. A total of 625 recipients were referred for heart transplantation, with the majority being male (n=412; 65.9%), while gender was undocumented for 69 cases (11.0%). The mean age was 38.1 (14.6) years, and 153 (24.5%) were listed for transplant, while 215 (34.4%) were deemed ineligible for listing. Contraindications for listing included social (n=106; 49.3%), medical (n=83; 38.6%) and psychological (n=26; 12.0%) factors, while 134 patients (21.4%) were considered too well. Poor social circumstances (n=38; 39.6%), poor insight (n=28; 29.2%) and poor compliance (n=21; 21.9%) were the most common non-medical reasons for not listing recipients, while obesity (n=30; 31.3%) and smoking (n=23; 24.0%) were notable medical contraindications. Forty-nine patients (7.8%) died during work-up, while 130 (85.0%) of the listed patients received a heart transplant. Of the 429 donor referrals, 139 (32.4%) were accepted for organ procurement. Reasons for declining donors included unsuitability for transplantation (30.3%), lack of capacity (1.8%), and recipient-donor mismatch (66.9%). Conclusion. Three-quarters of the referred patients were deemed unsuitable for heart transplantation for medical and/or social reasons. The ratio of referral to listing has decreased over time. However, once listed, the likelihood of receiving a transplant was high.

Background. Pulmonary endarterectomy (PEA) is the only definitive and potentially curative therapy for chronic thromboembolic pulmonary hypertension (CTEPH), associated with impressive improvements in symptoms and haemodynamics. However, it is only offered at a few centres in South Africa. The characteristics and outcomes of patients undergoing PEA in Cape Town have not been reported previously. Objectives. To assess the difference in World Health Organization functional class (WHO-FC) before and at least 6 weeks after surgery. Methods. We interrogated the adult cardiothoracic surgery database at the University of Cape Town between December 2005 and April 2021 for patients undergoing PEA at Groote Schuur Hospital and a private hospital. Results. A total of 32 patients underwent PEA, of whom 8 were excluded from the final analysis owing to incomplete data or a histological diagnosis other than CTEPH. The work-up of these patients for surgery was variable: all had a computed tomography pulmonary angiogram, 7 (29%) had a ventilation/perfusion scan, 5 (21%) underwent right heart catheterisation, and none had a pulmonary angiogram. The perioperative mortality was 4/24 (17%): 1 patient (4%) had a cardiac arrest on induction of anaesthesia, 2 patients (8%) died of postoperative pulmonary haemorrhage, and 1 patient (4%) died of septic complications in the intensive care unit. Among the survivors, the median (interquartile range) improvement in WHO-FC was 2 (1 - 3) classes (p=0.0004); 10/16 patients (63%) returned to a normal baseline (WHO-FC I). Conclusion. Even in a low-volume centre, PEA is associated with significant improvements in WHO-FC and a return to a normal baseline in survivors.

Background. Most asthma-related deaths occur in low- and middle-income countries, and South Africa (SA) is ranked fifth in global asthma mortality. Little is known about the characteristics and outcome of asthma patients requiring intensive care unit (ICU) admission in SA. Objectives. To identify and characterise patients with acute severe asthma admitted to the respiratory ICU at Groote Schuur Hospital, Cape Town, SA, in order to evaluate outcomes and identify predictors of poor outcomes in those admitted. Methods. We performed a retrospective descriptive study of patients with severe asthma admitted to the respiratory ICU at Groote Schuur Hospital between 1 January 2014 and 31 December 2019. Results. One hundred and three patients (110 admission episodes) were identified with an acute asthma exacerbation requiring ICU admission; all were mechanically ventilated. There was a female preponderance (53.6%; n=59/110), with a median (range) age overall of 33 (13 - 84) years. Of all admissions, 40 (36.4%) were current tobacco smokers and 16 (14.5%) patients with a history of substance abuse. Two thirds (60.0%; n=66/110) of the patients were using an inhaled corticosteroid (ICS). No predictors of mortality were evident in multivariate modelling, although those who died were older, and had higher Acute Physiology and Chronic Health Evaluation (APACHE II) scores and longer duration of admission. Only 59 of the surviving 96 individual patients (61.5%) attended a specialist pulmonology clinic after discharge. Conclusion. Among patients admitted to the respiratory ICU at Groote Schuur Hospital for asthma exacerbations, there was a high prevalence of smokers and poor coverage with inhaled ICSs. Although mortality was low compared with general ICU mortality, more needs to be done to prevent acute severe asthma exacerbations.

Background. Bronchiectasis is a chronic lung disorder that affects the lives of many South Africans. Post-tuberculosis (TB) bronchiectasis is an important complication of previous pulmonary TB and a common cause of bronchiectasis in South Africa (SA). No previous statements on the management of bronchiectasis in SA have been published. Objectives. To provide a position statement that will act as a template for the management of adult patients with bronchiectasis in SA. Methods. The South African Thoracic Society appointed an editorial committee to compile a position statement on the management of adult non-cystic fibrosis (CF) bronchiectasis in SA. Results. A position statement addressing the management of non-CF bronchiectasis in adults in SA was compiled. This position statement covers the epidemiology, aetiology, diagnosis, investigations and various aspects of management of adult patients with non-CF bronchiectasis in SA. Conclusion. Bronchiectasis has largely been a neglected lung condition, but new research has improved the outlook for patients. Collaboration between interprofessional team members in patient management is important. In SA, more research into the epidemiology of bronchiectasis, especially post-TB bronchiectasis and HIV-associated bronchiectasis, is required.

Abstract Background The mammalian retina contains an autonomous circadian clock that controls various aspects of retinal physiology and function, including dopamine (DA) release by amacrine cells. This neurotransmitter plays a critical role in retina development, visual signalling, and phase resetting of the retinal clock in adulthood. Interestingly, bidirectional regulation between dopaminergic cells and melanopsin-expressing retinal ganglion cells has been demonstrated in the adult and during development. Additionally, the adult melanopsin knockout mouse (Opn4 −/− ) exhibits a shortening of the endogenous period of the retinal clock. However, whether DA and / or melanopsin influence the retinal clock mechanism during its maturation is still unknown. Results Using wild-type Per2 Luc and melanopsin knockout (Opn4 −/− ::Per2 Luc ) mice at different postnatal stages, we found that the retina generates self-sustained circadian rhythms from postnatal day 5 in both genotypes and that the ability to express these rhythms emerges in the absence of external time cues. Intriguingly, only in wild-type explants, DA supplementation lengthened the endogenous period of the clock during the first week of postnatal development through both D1- and D2-like dopaminergic receptors. Furthermore, the blockade of spontaneous cholinergic retinal waves, which drive DA release in the early developmental stages, shortened the period and reduced the light-induced phase shift of the retinal clock only in wild-type retinas. Conclusions These data suggest that DA modulates the molecular core of the clock through melanopsin-dependent regulation of acetylcholine retinal waves, thus offering an unprecedented role of DA and melanopsin in the endogenous functioning and the light response of the retinal clock during development.

OBJECTIVES:. In patients with COVID-19 respiratory failure, controlled mechanical ventilation (CMV) is often necessary during the acute phases of the disease. Weaning from CMV to pressure support ventilation (PSV) is a key objective when the patient’s respiratory functions improve. Limited evidence exists regarding the factors predicting a successful transition to PSV and its impact on patient outcomes. DESIGN:. Retrospective observational cohort study. SETTING:. Twenty-four Italian ICUs from February 2020 to May 2020. PATIENTS:. Mechanically ventilated ICU patients with COVID-19-induced respiratory failure. INTERVENTION:. The transition period from CMV to PSV was evaluated. We defined it as “failure of assisted breathing” if the patient returned to CMV within the first 72 hours. MEASUREMENTS AND MAIN RESULTS:. Of 1260 ICU patients screened, 514 were included. Three hundred fifty-seven patients successfully made the transition to PSV, while 157 failed. Pao2/Fio2 ratio before the transition emerged as an independent predictor of a successful shift (odds ratio 1.00; 95% CI, 0.99–1.00; p = 0.003). Patients in the success group displayed a better trend in Pao2/Fio2, Paco2, plateau and peak pressure, and pH level. Subjects in the failure group exhibited higher ICU mortality (hazard ratio 2.08; 95% CI, 1.42–3.06; p < 0.001), an extended ICU length of stay (successful vs. failure 21 ± 14 vs. 27 ± 17 d; p < 0.001) and a longer duration of mechanical ventilation (19 ± 18 vs. 24 ± 17 d, p = 0.04). CONCLUSIONS:. Our study emphasizes that the Pao2/Fio2 ratio was the sole independent factor associated with a failed transition from CMV to PSV. The unsuccessful transition was associated with worse outcomes.

Background: The emergence of genetic variants of SARS-CoV-2 was associated with changing epidemiological characteristics throughout coronavirus disease 2019 (COVID-19) pandemic in population-based studies. Individual-level data on the clinical characteristics of infection with different SARS-CoV-2 variants in African countries is less well documented. Objectives: To describe the evolving clinical differences observed with the various SARS-CoV-2 variants of concern and compare the Omicron-driven wave in infections to the previous Delta-driven wave. Method: We performed a retrospective observational cohort study among patients admitted to a South African referral hospital with COVID-19 pneumonia. Patients were stratified by epidemiological wave period, and in a subset, the variants associated with each wave were confirmed by genomic sequencing. Outcomes were analysed by Cox proportional hazard models. Results: We included 1689 patients were included, representing infection waves driven predominantly by ancestral, Beta, Delta and Omicron BA1/BA2 BA4/BA5 variants. Crude 28-day mortality was 25.8% (34/133) in the Omicron wave period versus 37.1% (138/374) in the Delta wave period (hazard ratio [HR] 0.68 [95% CI 0.47–1.00] p = 0.049); this effect persisted after adjustment for age, gender, HIV status and presence of cardiovascular disease (adjusted HR [aHR] 0.43 [95% CI 0.28–0.67] p 0.001). Hospital-wide SARS-CoV-2 admissions and deaths were highest during the Delta wave period, with a decoupling of SARS-CoV-2 deaths and overall deaths thereafter. Conclusion: There was lower in-hospital mortality during Omicron-driven waves compared with the prior Delta wave, despite patients admitted during the Omicron wave being at higher risk. Contribution: This study summarises clinical characteristics associated with SARS-CoV-2 variants during the COVID-19 pandemic at a South African tertiary hospital, demonstrating a waning impact of COVID-19 on healthcare services over time despite epidemic waves driven by new variants. Findings suggest the absence of increasing virulence from later variants and protection from population and individual-level immunity.

Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a severe complication associated with a high mortality. However, evidence and guidance on management is sparse. The aim of this international survey was to assess differences in prevention, diagnostic and treatment strategies for AE-IPF in specialised and non-specialised ILD centres worldwide. Material and Methods: Pulmonologists working in specialised and non-specialised ILD centres were invited to participate in a survey designed by an international expert panel. Responses were evaluated in respect to the physicians institutions. Results: Three hundred and two (65%) of the respondents worked in a specialised ILD centre, 134 (29%) in a non-specialised pulmonology centre. Similarities were frequent with regards to diagnostic methods including radiology and screening for infection, treatment with corticosteroids, use of high-flow oxygen and non-invasive ventilation in critical ill patients and palliative strategies. However, differences were significant in terms of the use of KL-6 and pathogen testing in urine, treatments with cyclosporine and recombinant thrombomodulin, extracorporeal membrane oxygenation in critical ill patients as well as antacid medication and anaesthesia measures as preventive methods. Conclusion: Despite the absence of recommendations, approaches to the prevention, diagnosis and treatment of AE-IPF are comparable in specialised and non-specialised ILD centres, yet certain differences in the managements of AE-IPF exist. Clinical trials and guidelines are needed to improve patient care and prognosis in AE-IPF.

The use of Type IV cylinders for gas storage is becoming more widespread in various sectors, especially in transportation, owing to the lightweight nature of this type of cylinder, which is composed of a polymeric liner that exerts a barrier effect and an outer composite material shell that primarily imparts mechanical strength. In this work, the failure analysis of an HDPE liner in a Type IV cylinder for high-pressure storage was carried out. The breakdown occurred during a cyclic pressure test at room temperature and manifested in the hemispherical head area, as cracks perpendicular to the liner pinch-off line. The failed sample was thoroughly investigated and its characteristics were compared with those of other liners at different stages of production of a Type IV cylinder (blow molding, curing of the composite material). An examination of the liner showed that no significant chemical and morphological changes occurred during the production cycle of a Type IV cylinder that could justify the liner rupture, and that the most likely cause of failure was a design-related fatigue phenomenon.

In this Cochrane Corner, we highlight the main findings of a Cochrane Review by Flumignan et al. entitled ‘Anticoagulants for people hospitalised with COVID‐19’ and discuss the implications of these findings for research and practice in South Africa. In particular, we underscore the need for additional, high‐quality, randomised controlled trials comparing different intensities of anticoagulation in patients with COVID‐19 illness. Individuals in the intensive care unit and those hospitalised with another illness who are incidentally found to be infected with SARS‐CoV‐2 should still only be treated with prophylactic‐dose low‐molecular‐weight heparin.

A burgeoning epidemic of drug-resistant tuberculosis (TB) threatens to derail global control efforts. Although the mechanisms remain poorly clarified, drug-resistant strains are widely believed to be less infectious than drug-susceptible strains. Consequently, we hypothesized that lower proportions of patients with drug-resistant TB would have culturable Mycobacterium tuberculosis from respirable, cough-generated aerosols compared to patients with drug-susceptible TB, and that multiple factors, including mycobacterial genomic variation, would predict culturable cough aerosol production. We enumerated the colony forming units in aerosols (≤10 µm) from 452 patients with TB (227 with drug resistance), compared clinical characteristics, and performed mycobacterial whole-genome sequencing, dormancy phenotyping and drug-susceptibility analyses on M. tuberculosis from sputum. After considering treatment duration, we found that almost half of the patients with drug-resistant TB were cough aerosol culture-positive. Surprisingly, neither mycobacterial genomic variants, lineage, nor dormancy status predicted cough aerosol culture positivity. However, mycobacterial sputum bacillary load and clinical characteristics, including a lower symptom score and stronger cough, were strongly predictive, thereby supporting targeted transmission-limiting interventions. Effective treatment largely abrogated cough aerosol culture positivity; however, this was not always rapid. These data question current paradigms, inform public health strategies and suggest the need to redirect TB transmission-associated research efforts toward host-pathogen interactions.

We have presented the case of a symptomatic, primarily infected aortic pseudoaneurysm treated with endovascular stent graft exclusion and adjunctive use of a long-acting biocomposite antibiotic material injected directly into the pseudoaneurysm sac. We have described preparation of the biocomposite antibiotic material and the catheter-directed delivery technique in detail. Although the use of long-acting antibiotic materials such as antibiotic beads has been well described when performing open surgery in an infected field, the application of these materials in endovascular procedures has been less certain. The techniques we have described have the potential to promote field sterilization in a minimally invasive manner for patients with aortic infections who could be poor candidates for open surgery.

The recent pandemic has seen unprecedented demand for respiratory support of patients with COVID‐19 pneumonia, stretching services and clinicians. Yet despite the global numbers of patients treated, guidance is not clear on the correct choice of modality or the timing of escalation of therapy for an individual patient. This narrative review assesses the available literature on the best use of different modalities of respiratory support for an individual patient, and discusses benefits and risks of each, coupled with practical advice to improve outcomes. On current data, in an ideal context, it appears that as disease severity worsens, conventional oxygen therapy is not sufficient alone. In more severe disease, i.e. PaO2/FiO2 ratios below approximately 200, helmet‐CPAP (continuous positive airway pressure) (although not widely available) may be superior to high‐flow nasal cannula (HFNC) therapy or facemask non‐invasive ventilation (NIV)/CPAP, and that facemask NIV/CPAP may be superior to HFNC, but with noted important complications, including risk of pneumothoraces. In an ideal context, invasive mechanical ventilation should not be delayed where indicated and available. Vitally, the choice of respiratory support should not be prescriptive but contextualised to each setting, as supply and demand of resources vary markedly between institutions. Over time, institutions should develop clear policies to guide clinicians before demand exceeds supply, and should frequently review best practice as evidence matures.

Abstract Background There is still a paucity of evidence on the outcomes of coronavirus disease 2019 (COVID-19) among people living with human immunodeficiency virus (PWH) and those co-infected with tuberculosis (TB), particularly in areas where these conditions are common. We describe the clinical features, laboratory findings and outcome of hospitalised PWH and human immunodeficiency virus (HIV)-uninfected COVID-19 patients as well as those co-infected with tuberculosis (TB). Methods We conducted a multicentre cohort study across three hospitals in Cape Town, South Africa. All adults requiring hospitalisation with confirmed COVID-19 pneumonia from March to July 2020 were analysed. Results PWH comprised 270 (19%) of 1434 admissions. There were 47 patients with active tuberculosis (3.3%), of whom 29 (62%) were PWH. Three-hundred and seventy-three patients (26%) died. The mortality in PWH (n = 71, 26%) and HIV-uninfected patients (n = 296, 25%) was comparable. In patients with TB, PWH had a higher mortality than HIV-uninfected patients (n = 11, 38% vs n = 3, 20%; p = 0.001). In multivariable survival analysis a higher risk of death was associated with older age (Adjusted Hazard Ratio (AHR) 1.03 95%CI 1.02–1.03, p

Rett syndrome (RTT) is a X-linked neurodevelopmental disorder which represents the leading cause of severe incurable intellectual disability in females worldwide. The vast majority of RTT cases are caused by mutations in the X-linked MECP2 gene, and preclinical studies on RTT largely benefit from the use of mouse models of Mecp2, which present a broad spectrum of symptoms phenocopying those manifested by RTT patients.Neurons represent the core targets of the pathology; however, neuroanatomical abnormalities that regionally characterize the Mecp2 deficient mammalian brain remain ill-defined.Neuroimaging techniques, such as MRI and MRS, represent a key approach for assessing in vivo anatomic and metabolic changes in brain. Being non-invasive, these analyses also permit to investigate how the disease progresses over time through longitudinal studies.To foster the biological comprehension of RTT and identify useful biomarkers, we have performed a thorough in vivo longitudinal study of MRI and MRS in Mecp2 deficient mouse brains. Analyses were performed on both genders of two different mouse models of RTT, using an automatic atlas-based segmentation tool that permitted to obtain a detailed and unbiased description of the whole RTT mouse brain. We found that the most robust alteration of the RTT brain consists in an overall reduction of the brain volume. Accordingly, Mecp2 deficiency generally delays brain growth, eventually leading, in heterozygous older animals, to stagnation and/or contraction. Most but not all brain regions participate in the observed deficiency in brain size; similarly, the volumetric defect progresses diversely in different brain areas also depending on the specific Mecp2 genetic lesion and gender. Interestingly, in some regions volumetric defects anticipate overt symptoms, possibly revealing where the pathology originates and providing a useful biomarker for assessing drug efficacy in pre-clinical studies.

Here we report on Neanderthal engravings on a cave wall at La Roche-Cotard (LRC) in central France, made more than 57±3 thousand years ago. Following human occupation, the cave was completely sealed by cold-period sediments, which prevented access until its discovery in the 19th century and first excavation in the early 20th century. The timing of the closure of the cave is based on 50 optically stimulated luminescence ages derived from sediment collected inside and from around the cave. The anthropogenic origin of the spatially-structured, non-figurative marks found within the cave is confirmed using taphonomic, traceological and experimental evidence. Cave closure occurred significantly before the regional arrival of H. sapiens, and all artefacts from within the cave are typical Mousterian lithics; in Western Europe these are uniquely attributed to H. neanderthalensis. We conclude that the LRC engravings are unambiguous examples of Neanderthal abstract design.

Summary: Background: Surgery remains an adjunctive treatment for drug-resistant tuberculosis (DR-TB) treatment failure despite the use of bedaquiline. However, there are few data about the role of surgery when combined with newer drugs. There are no outcome data from TB endemic countries, and the prognostic significance of pre-operative PET-CT remains unknown. Methods: We performed a prospective observational study of 57 DR-TB patients referred for surgery at Groote Schuur Hospital between 2010 and 2016. PET-CT was performed if there was nodal disease or disease outside the area of planned resection but did not influence treatment decisions. 24-month treatment success post-surgery (cure or treatment completion), including all-cause mortality, was determined. Findings: 35/57 (61.4%) patients (median age 40 years; 26% HIV-infected) underwent surgery and 22/57 (38.6%) did not (11 patients were deemed unsuitable due to bilateral cavitary disease and 11 patients declined surgery). Treatment failure was significantly lower in those who underwent surgery compared to those eligible but declined surgery [15/35 (43%) versus 11/11 (100%); relative risk 0.57 (0.42–0.76); p

A partir de la declaración de la pandemia por el COVID-19, se inició un programa de reclusión domiciliaria y toda una serie de medidas para proteger a la población del contagio. La población mundial se enfrentó a dos situaciones críticas principales: el temor al contagio, y con ello a la muerte y, por otro lado, la crisis originada por el confinamiento. A raíz de este evento que afecta al mundo entero, se desarrolló una investigación cuyos objetivos se centraron en evaluar los estados emocionales y los recursos de afrontamiento empleados para amortiguar los efectos de la pandemia. Con este fin, se trabajó con una muestra de 1216 adultos argentinos, estableciendo una comparación durante los primeros 15 días, y luego a los 180 días del confinamiento. Adicionalmente, se propone identificar diferencias entre hombres y mujeres en estados emocionales y recursos empleados, como también se analizan y se especifican estos objetivos en población de riesgo por edad -mayores de 60 años-. Los resultados de esta investigación permiten reflexionar sobre los efectos psicológicos de la cuarentena y el confinamiento con respecto a los estados emocionales y la eficacia de los recursos utilizados; y en consecuencia se ofrecen datos que puedan permitir orientar a las políticas de salud mental a fin de poner en marcha programas de prevención primaria y post-pandemia.

Abstract Background Few studies detail the evolution of COVID-19 associated coagulopathy. We performed serial thromboelastography (TEG) and laboratory coagulation studies in 40 critically-ill, mechanically ventilated COVID-19 patients over a 14-day period and analysed differences between 30-day survivors and non-survivors. Methods Single-center prospective, observational study including 40 patients with severe COVID-19 pneumonia admitted to the intensive care unit (ICU) for mechanical ventilation. TEG analysis was performed on days 1, 7 and 14 of ICU admission and laboratory coagulation studies were performed on days 1 and 14. Coagulation variables were evaluated for change over the 14-day observation period. Differences between survivors and non-survivors at 30-days were analysed and compared. Results On admission, TEG maximum amplitude (MA) with heparinase correction was above the upper limit of the reference range in 32 (80%) patients while 33 (82.5%) presented with absent clot lysis at 30 min. The functional fibrinogen MA was also elevated above the upper limit of the reference range in 37 (92.5%) patients. All patients had elevated D-dimer and fibrinogen levels, mildly prolonged prothrombin times (PT), normal platelet counts and normal activated partial thromboplastin times (aPTT). The heparinase MA decreased significantly with time and normalised after 14 days (p =

Abstract Layer-by-layer (LbL) deposition method of polyelectrolytes is a versatile way of developing functional nanoscale coatings. Even though the mechanisms of LbL film development are well-established, currently there are no predictive models that can link film components with their final properties. The current health crisis has shown the importance of accelerated development of biomedical solutions such as antiviral coatings, and the implementation of machine learning methodologies for coating development can enable achieving this. In this work, using literature data and newly generated experimental results, we first analyzed the relative impact of 23 coating parameters on the coating thickness. Next, a predictive model has been developed using aforementioned parameters and molecular descriptors of polymers from the DeepChem library. Model performance was limited because of insufficient number of data points in the training set, due to the scarce availability of data in the literature. Despite this limitation, we demonstrate, for the first time, utilization of machine learning for prediction of LbL coating properties. It can decrease the time necessary to obtain functional coating with desired properties, as well as decrease experimental costs and enable the fast first response to crisis situations (such as pandemics) where coatings can positively contribute. Besides coating thickness, which was selected as an output value in this study, machine learning approach can be potentially used to predict functional properties of multilayer coatings, e.g. biocompatibility, cell adhesive, antibacterial, antiviral or anti-inflammatory properties.

Background: Haemorrhages in coronavirus disease 2019 (COVID-19) patients require proper knowledge and management. Objectives: To highlight the characteristics of haemorrhages in patients with COVID-19 infection. Method: A retrospective study examined CT scans performed over a 13-month period in patients hospitalised with COVID-19 infection to determine those who developed spontaneous bleeding. The authors also investigated correlations between the bleeding events and the patients’ characteristics. Results: Haemorrhages occurred in 2.22% (31/1396) of patients hospitalised with COVID-19 infection (7.88%, 19/241 in the intensive care unit). Bleeding, major in most cases, occurred in anticoagulated patients, especially males with multiple comorbidities, aged between 60 and 79 years and mainly appeared in a single anatomical region (especially retroperitoneal), with the most voluminous in the chest wall. The complication was diagnosed on average 16.7 days after admission and occurred predominantly in critically ill patients undergoing invasive ventilation and pronation-supination cycles. In just under half of the cases, the haematomas were active, and in these cases, mainly with a single contrast blush and with earlier onset after the start of anticoagulation than in non-active bleeding. Major bleeding was also earlier in the presence of multiple morbidity. The vast majority of patients were treated conservatively and survived. Conclusion: At COVID-19 hospital centres, it is advisable that there is knowledge of such a complication for which CT imaging is essential for diagnosis and proper management. Although some authors have expressed doubts about anticoagulant treatment in patients with COVID-19, the bleeding complication in this study did not significantly affect the outcome. Contribution: Spontaneous haemorrhage did not significantly affect the outcome in this series.

Patients with chronic headaches sometimes prefer non-pharmacological methods for pain management. We have shown previously that green light exposure (GLED, Green Light Emitting Diode) reversed thermal hyperalgesia and mechanical allodynia in a rat model of neuropathic pain. This effect is mediated through the visual system. Moreover, we recently showed that GLED was effective in decreasing the severity of headache pain and the number of headache-days per month in migraine patients. The visual system is comprised of image-forming and non-image-forming pathways; however, the contribution of different photosensitive cells to the effect of GLED is not yet known. Here, we report a 66-year-old man with headaches attributed to other disorders of homeostasis and color blindness who was recruited in the GLED study. The subject, diagnosed with protanomaly, cannot differentiate green, yellow, orange, and red colors. After completing the GLED exposure protocol, the subject noted significant decreases in headache pain intensity without reduction in the number of headache-days per month. The subject also reported improvement in the quality of his sleep. These findings suggest that green light therapy mediates the decrease of the headache pain intensity through non-image-forming intrinsically photosensitive retinal ganglion cells. However, the subject did not report a change in the frequency of his headaches, suggesting the involvement of cones in reduction of headache frequency by GLED. This is the first case reported of a colorblind man with chronic headache using GLED to manage his headache pain and may increase our understanding of the contribution of different photosensitive cells in mediating the pain-relieving effects of GLED.

Gynecologist and plastic surgeons pioneered the application of lasers in medicine and surgery almost 5 decades ago, initially used to treat cervical and vaginal pathologies. Ever since, energy-based devices have been deployed to treat pelvic pathologies and improve fertility. Recent technological developments triggered an unprecedented wave of publications, assessing the efficacy of fractional laser, and radiofrequency on the vaginal wall in reversing natural aging processes. Studies have shown that a certain degree of thermal energy deposited on the vaginal wall stimulates proliferation of the glycogen-enriched epithelium, neovascularization, and collagen formation in the lamina propria, and improves natural lubrication and control of urination. This review aimed to review such data and to guide future research. A unique assembly of experts from around the globe, compiled and edited this manuscript based on a thorough literature review and personal experience. Lasers Surg. Med. 49:137-159, 2017. © 2017 Wiley Periodicals, Inc.

Abstract Background Only 55% of multidrug-resistant tuberculosis (MDR-TB) cases worldwide complete treatment, with problem substance use a risk for default and treatment failure. Nevertheless, there is little research on psychotherapeutic interventions for reducing substance use amongst MDR-TB patients, in general, and on their delivery by non-specialist health workers in particular. Objectives To explore the feasibility and acceptability of a non-specialist health worker-delivered 4-session brief motivational interviewing and relapse prevention (MI-RP) intervention for problem substance use and to obtain preliminary data on the effects of this intervention on substance use severity, depressive symptoms, psychological distress and functional impairment at 3 months after hospital discharge. Methods Between December 2015 and October 2016, consenting MDR-TB patients admitted to Brewelskloof Hospital who screened at moderate to severe risk for substance-related problems on the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) were enrolled, and a baseline questionnaire administered. In the 4 weeks prior to planned discharge, trained counsellors delivered the MI-RP intervention. The baseline questionnaire was re-administered 3 months post-discharge and qualitative interviews were conducted with a randomly selected sample of participants (n = 10). Results Sixty patients were screened: 40 (66%) met inclusion criteria of which 39 (98%) were enrolled. Of the enrolled patients, 26 (67%) completed the counselling sessions and the final assessment. Qualitative interviews revealed participants’ perceptions of the value of the intervention. From baseline to follow-up, patients reported reductions in substance use severity, symptoms of depression, distress and functional impairment. Conclusion In this feasibility study, participant retention in the study was moderate. We found preliminary evidence supporting the benefits of the intervention for reducing substance use and symptoms of psychological distress, supported by qualitative reports of patient experiences. Randomised studies are needed to demonstrate efficacy of this intervention before considering potential for wider implementation. Trial registration South African National Clinical Trials Register ( DOH-27-0315-5007 ) on 01/04/2015 ( http://www.sanctr.gov.za )

An improved understanding of an ovary’s structures is highly desirable to support advances in folliculogenesis knowledge and reproductive medicine, with particular attention to fertility preservation options for prepubertal girls with malignant tumors. Although currently the golden standard for structural analysis is provided by combining histological sections, staining, and visible 2D microscopic inspection, synchrotron radiation phase-contrast microtomography is becoming a new challenge for three-dimensional studies at micrometric resolution. To this aim, the proper use of contrast agents can improve the visualization of internal structures in ovary tissues, which normally present a low radiopacity. In this study, we report a comparison of four staining protocols, based on iodine or tungsten containing agents, applied to bovine ovarian tissues fixed in Bouin’s solution. The microtomography (microCT) analyses at two synchrotron facilities under different set-ups were performed at different energies in order to maximize the image contrast. While tungsten-based agents allow large structures to be well identified, Iodine ones better highlight smaller features, especially when acquired above the K-edge energy of the specific metal. Further scans performed at lower energy where the setup was optimized for overall quality and sensitivity from phase-contrast still provided highly resolved visualization of follicular and intrafollicular structures at different maturation stages, independent of the staining protocol. The analyses were complemented by X-ray Fluorescence mapping on 2D sections, showing that the tungsten-based agent has a higher penetration in this type of tissues.

Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a severe complication associated with a high mortality. However, evidence and guidance on management is sparse. The aim of this international survey was to assess differences in prevention, diagnostic and treatment strategies for AE-IPF in specialised and non-specialised ILD centres worldwide.Material and Methods: Pulmonologists working in specialised and non-specialised ILD centres were invited to participate in a survey designed by an international expert panel. Responses were evaluated in respect to the physicians' institutions.Results: Three hundred and two (65%) of the respondents worked in a specialised ILD centre, 134 (29%) in a non-specialised pulmonology centre. Similarities were frequent with regards to diagnostic methods including radiology and screening for infection, treatment with corticosteroids, use of high-flow oxygen and non-invasive ventilation in critical ill patients and palliative strategies. However, differences were significant in terms of the use of KL-6 and pathogen testing in urine, treatments with cyclosporine and recombinant thrombomodulin, extracorporeal membrane oxygenation in critical ill patients as well as antacid medication and anaesthesia measures as preventive methods.Conclusion: Despite the absence of recommendations, approaches to the prevention, diagnosis and treatment of AE-IPF are comparable in specialised and non-specialised ILD centres, yet certain differences in the managements of AE-IPF exist. Clinical trials and guidelines are needed to improve patient care and prognosis in AE-IPF.