A neglected source of household air pollution: a preliminary, mixed methods study of purposely produced household smoke in Wollo, Ethiopia.

BACKGROUND: Ill health associated with household air pollution (HAP) is increasingly recognized as a public health problem in sub-Saharan Africa. To date, attempts to reduce HAP have focussed on smoke from cooking fires and have ignored traditional cultural practices which generate purposely produced smoke (PPS). This study aimed to investigate PPS prevalence, reasons for use and safety perceptions. METHODS: The study was conducted in Wollo, Ethiopia, and used a mixed methods approach of quantitative surveys (analysed descriptively) and qualitative interviews with householders and healthcare workers (analysed thematically). RESULTS: PPS use was reported by 99% of survey respondents and it was considered a fundamental part of life. Although reasons for use included housekeeping, culture/religion and well-being, coffee ceremony was most commonly cited (44% of respondents). Both householders and healthcare workers appeared to assume PPS is safe, except for people with certain underlying conditions. Healthcare workers felt the lack of evidence of harm from PPS meant there was no justification for intervention. CONCLUSION: This study, the first in-depth study of PPS, has shown its use to be widespread, with many perceived benefits and thus a very important part of local culture in this sample Ethiopian community. Consequently, any public health interventions aimed at reducing HAP in this setting need to consider PPS.

Bacteriology of endotracheal tube biofilms and antibiotic resistance: a systematic review.

Bacteria commonly adhere to surfaces and produce polymeric material to encase the attached cells to form communities called biofilms. Within these biofilms, bacteria can appear to be many times more resistant to antibiotics or disinfectants. This systematic review explores the prevalence and microbial profile associated with biofilm production of bacteria isolated from endotracheal tubes and its associations with antimicrobial resistance. A comprehensive search was performed on databases PubMed, Embase, and Google Scholar for relevant articles published between 1st January 2000 and 31st December 2022. The relevant articles were exported to Mendeley Desktop 1.19.8 and screened by title and abstract, followed by full text screening based on the eligibility criteria of the study. Quality assessment of the studies was performed using the Newcastle-Ottawa Scale (NOS) customized for cross-sectional studies. Furthermore, the prevalence of antimicrobial resistance in biofilm-producers isolated from endotracheal tube specimens was investigated. Twenty studies encompassing 981 endotracheal tubes met the eligibility criteria. Pseudomonas spp. and Acinetobacter spp. were predominant isolates among the biofilm producers. These biofilms provided strong resistance against commonly used antibiotics. The highest resistance rate observed in Pseudomonas spp. was against fluoroquinolones whereas the least resistance was seen against piperacillin-tazobactam. A similar trend of susceptibility was observed in Acinetobacter spp. with a very high resistance rate against fluoroquinolones, third-generation cephalosporins and carbapenems. In conclusion, endotracheal tubes were associated with colonization by biofilm forming bacteria with varying levels of antimicrobial resistance. Biofilms may promote the occurrence of recalcitrant infections in endotracheal tubes which need to be managed with appropriate protocols and antimicrobial stewardship. Research focus should shift towards meticulous exploration of biofilm-associated infections to improve detection and management.

Total Joint Arthroplasty at a Tertiary Military Medical Center in Hawai'i: Does Travel Distance Influence Short Term Complications?

As the health care delivery system in the United States changes, there has been an increase in the presence of specialized medical centers, translating into increased travel distance for patients. Tripler Army Medical Center in Honolulu, Hawai'i serves a unique population of local patients and those traveling from neighboring Hawaiian Islands and from across the Pacific Basin and Asia. Previous studies have examined the role of distance traveled, but no study has looked at patients routinely flying in the immediate postoperative period. The purpose of this study is to investigate if increased travel distance is associated with a higher probability of complications after a total joint arthroplasty (TJA). A retrospective review of all patients receiving TJA at a single medical institution was performed. After meeting the inclusion criteria, 126 consecutive patients were reviewed for 30-day complications. Sixty-four patients were local (from O'ahu, Hawai'i), and 13 from neighboring Hawaiian Islands, while 49 were international. There were no significant differences in complications between the groups. Length of stay was not affected by distance. A significant risk factor for short-term complications was having a higher score based on the American Society of Anesthesiologists Physical Status Classification System (ASA), ASA 3 vs ASA 1&2 (14% vs 1%, P = .015). There were no findings in our population to support inferior outcomes in patients traveling from the outer Pacific Basin during their initial postoperative course compared to the local population. No patient sustained a short-term complication after a patient returned to their island or country of origin. The results of this study will help to guide clinical decision making and effective resource management for patients seeking TJA traveling from a significant distance.

Effects of Linear Periodization Training on Performance Gains and Injury Prevention in a Garrisoned Military Unit.

PURPOSE: Performing well in combat requires military service members to be in peak physical shape. Although each branch of the United States military has fitness guidelines and assessments, there are no exact prescriptions for physical training programs. The absence of a standardised approach may lead to suboptimal physical performance and increased risk of musculoskeletal injury. To address this gap, we evaluated the feasibility of a pilot combat conditioning program based on linear periodisation. METHODS: Twenty-nine garrisoned US Marine Corps service members (25 men, 4 women; 23.5±4.4 years) enrolled in our 11-week conditioning program that was supervised by a strength and conditioning professional. Military-specific (physical/combat fitness tests) and general (treadmill-based maximal exercise test) assessments were performed at baseline and 11 weeks. Training and injury logs were maintained throughout the duration of the program. RESULTS: Approximately 80% (23/29) of service members completed the entire program. Cardiorespiratory fitness (Peak VO2; +8.10±10.9%; p=0.011), upper-body strength (pull-ups; +47.0±58.2%; p<0.001) and core strength (abdominal crunches; +9.2±23.3%; p=0.029) significantly increased from pre- to post-training. No statistically significant improvement or worsening was noted in any other performance assessment measure. Eight (28%) participants reported minor musculoskeletal concerns, of which only one required medical attention (injury rate 1.3 injuries/100 person-months). CONCLUSION: A protocolised linear periodisation training program was feasible and demonstrated improvements in fitness in a group of garrisoned Marines with low injury rates. Other military units may benefit from a similar approach.

Posterior Malleolus Arthroscopic Reduction and Internal Fixation Technique.

Adequate reduction of posterior malleolar fractures leads to better outcomes. Arthroscopic reduction and internal fixation presents an opportunity for excellent reduction with a minimally invasive approach. Herein, we present a technique with some discussion on outcomes.

Effectiveness of the probiotic Streptococcus salivarius K12 for the treatment and/or prevention of sore throat: a systematic review.

BACKGROUND: Sore throat resulting from pharyngotonsillitis is one of the commonest reasons for primary care consultation and inappropriate antibiotic prescription and finding effective alternative treatments is important. OBJECTIVES: To review the evidence for using the probiotic Streptococcus salivarius K12 (SsK12) for the prevention or treatment of pharyngotonsillitis. DATA SOURCES: PubMed, Embase, CINAHL and Cochrane Library. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs). PARTICIPANTS: Adults or children. INTERVENTIONS: SsK12 as active treatment or prophylaxis, against pharyngotonsillitis. METHODS: Literature search. RESULTS: Four articles were identified (1846 participants). All were deemed to be of poor quality using the Cochrane risk-of-bias assessment. Two trials studied SsK12 prophylaxis for streptococcal pharyngitis (children without history of recurrence). One compared daily administration of SsK12 to no treatment over 6 months (n = 222, age 33-45 months), reporting significantly lower incidence in the SsK12 group (16.2% vs. 48.6%, p < 0.01), whereas another placebo-controlled RCT over four school terms (n = 1314, 5-14 years) found no significant difference (7.8% vs. 8.8%, p 0.34) with SsK12 (administered on school days). Another trial found daily SsK12 to significantly protect children (n = 250, 6-7 years) against chronic adenoiditis exacerbation over 3 months compared to no treatment (71.7% vs. 100%, p < 0.0001). The one placebo-controlled RCT in adults that studied the use of SsK12 for acute pharyngotonsillitis (concurrently with penicillin) showed no significant benefit. In all trials, SsK12 was safe and well tolerated. CONCLUSIONS: SsK12 appears safe and well tolerated. However, further RCTs are required to establish its role as a prophylactic therapy, particularly among patients experiencing frequent exacerbations of pharyngitis. In the acute setting, SsK12 is unlikely to be effective if given concurrently with antibiotics; however, further RCTs should establish its role as an alternative to antibiotics in nonsevere cases or when prescribed after antibiotic therapy for the prevention of disease recurrence and/or secondary infection.

Uva-ursi extract and ibuprofen as alternative treatments for uncomplicated urinary tract infection in women (ATAFUTI): a factorial randomized trial.

OBJECTIVES: The aim was to investigate if offering symptomatic therapy (Uva-ursi or ibuprofen) alongside a delayed prescription would relieve symptoms and reduce the consumption of antibiotics for adult women presenting with acute uncomplicated urinary tract infection (UTI). METHODS: A 2 × 2 factorial placebo controlled randomized trial in primary care. The participants were 382 women aged 18-70 years with symptoms of dysuria, urgency, or frequency of urination and suspected by a clinician to have a lower UTI. The interventions were Uva-ursi extract and/or ibuprofen advice. All women were provided with a delayed or 'back-up' prescription for antibiotics. Missing data were imputed using multiple imputation methods (ISRCTN registry: ISRCTN43397016). RESULTS: An ITT analysis of mean score for frequency symptoms assessed on Days 2-4 found no evidence of a difference between Uva-ursi vs. placebo -0.06 (95% CI -0.33 to 0.21; p 0.661), nor ibuprofen vs. no ibuprofen advice -0.01 (95% CI -0.27 to 0.26; p 0.951). There was no evidence of a reduction in antibiotic consumption with Uva-ursi (39.9% vs. placebo 47.4%; logistic regression odds ratio (OR) 0.59 (95% CI 0.22-1.58; p 0.293) but there was a significant reduction for ibuprofen advice (34.9% vs. no advice 51.0%; OR 0.27 (95% CI 0.10 to 0.72; p 0.009). There were no safety concerns and no episodes of upper tract infection were recorded. CONCLUSIONS: We found no evidence of an effect of either intervention on the severity of frequency symptoms. There is evidence that advice to take ibuprofen will reduce antibiotic consumption without increasing complications. For every seven women given this advice, one less will use antibiotics.

Ethnopharmacology and malaria: new hypothetical leads or old efficient antimalarials?

New treatments are urgently needed to curb and eradicate malaria in developing countries. As most people living in malarial endemic areas use traditional medicine to fight this disease, why have new treatments not emerged recently from ethnopharmacology-oriented research? The rationale and limitations of the ethnopharmacological approach are discussed in this paper, focusing on ethnopharmacology methodologies and techniques used for assessing botanical samples for their antimalarial properties. Discrepancies often observed between strong ethnopharmacological reputation and laboratory results are discussed, as well as new research perspectives.

A novel cationic-peptide coating for the prevention of microbial colonization on contact lenses.

AIMS: To develop an antimicrobial peptide with broad spectrum activity against bacteria implicated in biomaterial infection of low toxicity to mammalian cells and retaining its antimicrobial activity when covalently bound to a biomaterial surface. METHODS AND RESULTS: A synthetic peptide (melimine) was produced by combining portions of the antimicrobial cationic peptides mellitin and protamine. In contrast to the parent peptide melittin which lysed sheep red blood cells at >10 microg ml(-1), melimine lysed sheep red blood cells only at concentrations >2500 microg ml(-1), well above bactericidal concentrations. Additionally, melimine was found to be stable to heat sterilization. Evaluation by electron microscopy showed that exposure of both Pseudomonas aeruginosa and Staphylococcus aureus to melimine at the minimal inhibitory concentration (MIC) produced changes in the structure of the bacterial membranes. Further, repeated passage of these bacteria in sub-MIC concentrations of melimine did not result in an increase in the MIC. Melimine was tested for its ability to reduce bacterial adhesion to contact lenses when adsorbed or covalently attached. Approximately 80% reduction in viable bacteria was seen against both P. aeruginosa and S. aureus for 500 microg per lens adsorbed melimine. Covalently linked melimine (18 +/- 4 microg per lens) showed >70% reduction of these bacteria to the lens. CONCLUSIONS: We have designed and tested a synthetic peptide melimine incorporating active regions of protamine and mellitin which may represent a good candidate for development as an antimicrobial coating for biomaterials. SIGNIFICANCE AND IMPACT OF THE STUDY: Infection associated with the use of biomaterials remains a major barrier to the long-term use of medical devices. The antimicrobial peptide melimine is an excellent candidate for development as an antimicrobial coating for such devices.

Inflammasomes, the eye and anti-inflammasome therapy.

Inflammasomes, key molecular regulators that play an important role in inflammation, consist of a central protein, an adaptor protein ASC (apoptosis speck-like protein) and a caspase-1 protein. Upon activation, caspase-1 induces maturation of cytokines such as interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). The release of these cytokines can result in inflammation. Inflammasomes are activated by a variety of factors and their activation involves complex signalling leading to resolution of infection, but can also contribute to the pathology of inflammatory, autoimmune, and infectious diseases. The role of NLRP1, NLRP3, NLRC4 and AIM2 inflammasomes in the pathogenesis of ocular diseases such as glaucoma, age related macular degeneration (AMD), diabetic retinopathy, dry eye and infections of the eye has been established over the past decade. In experimental studies and models, inhibition of inflammasomes generally helps to reduce the inflammation associated with these eye diseases, but as yet the role of these inflammasomes in many human eye diseases is unknown. Therefore, a need exists to study and understand various aspects of inflammasomes and their contribution to the pathology of human eye diseases. The goal of this review is to discuss the role of inflammasomes in the pathology of eye diseases, scope for anti-inflammasome therapy, and current research gaps in inflammasome-related eye disease.

The effect of short term contact lens wear on the tear film and ocular surface characteristics of tolerant and intolerant wearers.

The purpose of this study was to determine the effect of contact lens wear on the tear film and ocular surface of people tolerant or intolerant to contact lens wear. Twenty subjects participated; 11 tolerants and nine intolerants. Their baseline tear film (no lens wear) was analysed with a range of clinical measurements and protein analyses (lactoferrin, sIgA and lysozyme). The tests were then repeated at the end of 6h of contact lens wear during the day and while lenses were worn. Both tolerants and intolerants showed statistically significant increases in bulbar and overall conjunctival redness after 6h of lens wear. For tolerants only, there was a statistically significant increase in the tear film meniscus area (0.08 mm(2) +/- 0.04 compared to 0.14 mm(2) +/- 0.06 (p = 0.023)) and a statistically significant decrease in the non-invasive tear film break-up time (NI-TBUT; 21.3 s +/- 5.7 compared to 3.7 s +/- 4.3 (p = 0.003)) after 6h of lens wear. There were no changes in other tear film or ocular surface parameters. The protein concentration and lipid layer appearance did not change during lens wear for either population. Prior to lens wear, tolerant subjects had a statistically longer NI-TBUT, higher phenol red thread test and higher tear flow rate. After 6h of lens wear and while wearing lenses, all but NI-TBUT remained statistically different. Lens wear affected only a small number of clinical variables and 6h wear did not effect the concentration of those proteins measured in tears in this study.

Towards a closed eye model of the pre-ocular tear layer.

Although the tear film has been extensively studied as it exists in the open eye state, until recently very little was known as to what happens to the tear film on eye closure. Recent studies have shown that eye closure results in a profound change in the composition, origins, turnover and physiological functions of the tear film. These changes include a shift from an inducible, neurologically controlled, lacrimal secretion containing among other proteins primarily lysozyme, lactoferrin and tear specific lipocalin, to a much slower, constitutive-type of secretion, composed almost exclusively of sIgA. This change is accompanied by the build-up of sialoglycoproteins of epithelial and goblet cell origin, the build-up and activation of complement and the build-up of serum proteins. In addition, various cytokines and proinflammatory mediators accumulate, including some which are potent inducers of angiogenesis and leukochemotaxis. The closed eye also exhibits the recruitment and activation of massive numbers of PMN cells. This results in a stagnant, closed eye layer, which is extremely rich in reactive complement products, PMN cell proteases including protease-3, elastase, capthepsin G, MMP-9 and urokinase. We have postulated that this shift represents a fundamental change in host-defense strategies from a passive-barrier defense to an active immune, inflammatory, phagocyte-mediated process and that this shift is necessitated in order to protect the cornea from entrapped microorganisms. Studies have shown that autologous cell damage is avoided in closed eye tear fluid, by the accumulation of several modulators of complement activation, which shift activation towards opsonization of entrapped microorganisms and the build-up of a wide array of antiproteases. Some of the latter are likely to arise from the ocular surface tissues. Corneal neovascularization may be avoided in part by the build-up of alpha2-macroglobulin and the conversion of plasminogen to angiostatin. It is highly probable that other bioactive protein fragments are produced in the closed eye, which contribute to homeostasis. Areas of future study are indicated.

Liver fatty acids and the sudden infant death syndrome.

Fatty acid analyses were performed on samples of liver from 325 human infants less than 1 yr old, 275 of whom had died of sudden infant death syndrome (SIDS), and 50 of other causes (non-SIDS). Data for fatty acid composition were analyzed in relation to cause of death, age of infant, liver biotin, liver metals, and other variables by a variety of statistical methods. There were significant differences in the levels of liver fatty acids between SIDS and non-SIDS infants in the age group 1 to 6 months, notably in that the fatty acids of the SIDS infants appeared to have lower levels of dihomo-gamma-linolenic acid, which is the precursor of the "1-series" prostaglandins. Statistically significant relationships were observed between various fatty acids, and there were also significant relationships involving docosapentaenoic acid and infant age, and docosahexaenoic acid and liver iron content.

Association of enzyme inhibition with methods of museum skin preparation.

Enzyme inhibition is commonly encountered when using molecular biological techniques on museum-prepared animal skin samples, and this problem is exacerbated by a lack of information on how particular skins have been prepared for preservation. This report: (i) demonstrates that while some methods of museum preparation inhibit both proteinase K digestion and the PCR, others do not; (ii) describes a change in buffer conditions that reduces proteinase K enzyme inhibition during tissue digestion: and (iii) uses electron-dispersive X-ray microanalysis (EDXA) to show that the preparation methods for museum-preserved skin are often more complex than the treatment description provided with samples and also suggests that some of these descriptions are incorrect.

Cytochemical reactions of human hematopoietic cells in liquid culture.

Growth of human bone marrow in liquid suspension cultures has been used to study normal hematopoietic cell differentiation and abnormalities in blood diseases. A variety of cytochemical stains were applied to human marrow cells cultured in vitro for up to 14 days. AS-D- CHLOROACETATE ESTERASE AND ALPHA-NAPHYHYL BUTYrate esterase were most useful in distinguishing different cell lines in culture. Peroxidase activity disappeared with mononuclear phagocyte morphogenesis and diminished with culture in intermediate and mature granulocytes. Acid phosphatase activity and methyl greed pyronin staining intensity increased with macrophage maturation.

Complement and complement regulatory proteins in human tears.

PURPOSE: The complement system is part of the innate defense system of the body, and it contributes to inflammatory conditions. The current study examined tears for the presence of complement components, the activity of the components, and the presence of regulatory components. METHODS: The significance of a functional complement system in tears was examined in four ways. First, the presence and concentration of complement components in tear samples (open-eye, closed-eye, and reflex tears) was examined by sandwich enzyme-linked immunosorbent assay. Second, the presence of an active pathway in each tear type was established by supplementation of complement-deficient sera. Third, Western blotting of tear samples was used to determine whether complement components were activated in tears. Fourth, the presence of regulatory components was examined by enzyme-linked immunosorbent assay and by the inhibition of the ability of tears to supplement deficient sera. RESULTS: Components C1q, C3, factor B, C4, C5, and C9 were detected in closed-eye tears. Only C3, factor B, and C4 were detected in open-eye and reflex tears. Tears were able to supplement complement-deficient sera, indicating that the components were in an active state. Complement components C3, factor B, C4, and C9 were activated in closed-eye tears. The regulatory protein decay-accelerating factor was found only in closed-eye tears. Lactoferrin, another regulatory protein present in all tear types, was shown to inhibit complement-mediated red blood cell lysis, although the inhibition by closed-eye tear lactoferrin was reduced compared to that isolated from other tear types. CONCLUSIONS: This study has demonstrated that the complement system in tears was functionally active and that the concentration of all components was increased greatly in closed-eye tears. In spite of the presence of regulatory proteins, proteins of the complement cascade in tears were shown to be activated.

Staphylococcus corneal virulence in a new topical model of infection.

PURPOSE: To develop a topical inoculation model of Staphylococcus aureus keratitis in which scarification, contact lenses, and spermidine are used to inhibit the host defenses and to investigate the role of alpha-toxin in this infection. METHODS: An alpha-toxin-positive parent strain (8325-4), its isogenic alpha-toxin-negative mutant (DU1090), and a genetically rescued form of the mutant (DU1090/pDU1212) were bound to rabbit-specific contact lenses, treated with spermidine (50 mM), and applied to scarified rabbit corneas. Eyes were treated topically with spermidine before and after lens application. Eyes were graded for disease by slit lamp examination (SLE) every 6 hours until 24 hours PI (PI), and erosion diameters were measured. Histopathologic changes and colony forming units (CFUs) of bacteria were determined. RESULTS: Spermidine treatment and inoculation of eyes with Staphylococcus on contact lenses resulted in significant increases in both CFUs per cornea (P = 0.0041) and SLE score (P or= 0.1959) multilog increase in CFUs over the inoculum at 24 hours PI. The alpha-toxin-producing strains, 8325-4 and DU1090/pDU1212, caused significantly more disease than the alpha-toxin-deficient mutant DU1090 at 24 hours PI (P

Fibronectin in the tear film.

PURPOSE: Fibronectin plays an important role in corneal healing and has been detected previously in the tear film. To investigate the levels of fibronectin in normal human tears, the authors measured and compared fibronectin concentration in open-eye, closed-eye, and reflex tear fluid. The origin of fibronectin in the tear film was investigated by comparing fibronectin concentration in sequentially collected reflex tear samples with the concentrations of total protein and albumin in the same samples. METHODS: Open-eye and closed-eye tears were collected from 11 noncontact lens wearers. From 7 subjects, 20 uninterrupted reflex tear samples (10 microliters each) subsequently were collected, using the sneeze reflex method of stimulation, followed by an additional 10 nonstimulated tear samples (3 microliters each) immediately after cessation of stimulus. Enzyme-linked immunosorbent assays were used to determine fibronectin and albumin concentrations, and bicinchoninic acid protein assays were used to determine total protein concentration in each sample. RESULTS: Fibronectin concentration in open-eye tears (19 +/- 24 eta g/ml, range 3 to 78 eta g/ml) was significantly different (P = 0.004) from that in closed-eyes tears (4127 +/- 3222 eta g/ml, range 1177 to 11384 eta g/ml). In the first 50 microliters of reflex tears, fibronectin concentrations were low (10 +/- 23 eta g/ml), but they increased significantly (P = 0.028) after 100 microliters of reflex tears had been collected (220 +/- 126 eta g/ml). There was a further marked transient increase (767 +/- 946 eta g/ml) after cessation of stimulus. Total protein concentration in the same samples decreased significantly during reflex tear collection compared to open-eye tears, and it increased gradually after cessation of stimulus. Albumin concentration in the same samples, analyzed for two subjects only, showed a pattern similar to that for fibronectin. Dilation of conjunctival blood vessels was noted in all subjects after reflex tear collection. Administration of a topical vasoconstrictor in two subjects eliminated the increase in fibronectin concentration during reflex tearing but did not affect total protein concentration. Under reducing conditions, the molecular mass of fibronectin in open-eye and reflex tears was 240 kDa, identical to commercially available purified plasma fibronectin, whereas fibronectin in closed-eye tears was degraded into small molecular mass fragments. CONCLUSIONS: These findings suggest that fibronectin in tear fluid is derived from plasma and that the increase in concentration in closed-eye and reflex tear fluid is caused by leakage from dilated conjunctival blood vessels.