Low household income increases the risk of tuberculosis recurrence: a retrospective nationwide cohort study in South Korea.

OBJECTIVES: We assessed the impact of household income on tuberculosis (TB) recurrence and the long-term impact of TB on household income. STUDY DESIGN: This was a retrospective nationwide cohort study of patients with drug-susceptible TB (DS-TB) and TB recurrence. METHODS: Using the South Korean national TB cohort database, we identified a sub-set cohort of patients with newly diagnosed drug-susceptible TB between 2013 and 2016 and tracked their TB recurrence and longitudinal income data from 2007 to 2018. Income levels were evaluated as 'Medical aid' and quintile categories. To assess risk factors associated with TB recurrence, we used a sub-distribution hazard model, adjusting for the competing risks of death. RESULTS: Of 66,690 patients successfully treated with DS-TB, 2095 (3.1 %) experienced recurrence during a median follow-up of 39 months. The incidence of TB recurrence was 982.1/100,000 person-years, with 50.3 % of the recurrences occurring within 1 year of treatment completion. The risk of TB recurrence increased with decreasing income levels, with the highest risk observed in the lowest income group. The effect of income on TB recurrence was prominent in males but not in females. Overall, patients with TB recurrence experienced a linear decline in income levels, compared with those without recurrence. CONCLUSIONS: Household income during the initial TB episode was an important risk factor for TB recurrence, particularly in males.

To Test or Not? Xpert MTB/RIF as an Alternative to Smear Microscopy to Guide Line Probe Assay Testing for Drug-Resistant Tuberculosis.

Xpert MTB/RIF (Xpert) revolutionized tuberculosis (TB) diagnosis. Laboratory decision making on whether widely-used reflex drug susceptibility assays (MTBDRplus, first-line resistance; MTBDRsl, second-line) are conducted is based on smear status, with smear-negative specimens often excluded. We performed receiver operator characteristic (ROC) curve analyses using bacterial load information (smear microscopy grade, Xpert-generated semi-quantitation categories and minimum cycle threshold [CTmin] values) from Xpert rifampicin-resistant sputum for the prediction of downstream line probe assay results as "likely non-actionable" (no resistance or susceptible results generated). We evaluated actionable-to-non-actionable result ratios and pay-offs with missed resistance versus LPAs done universally. Smear-negatives were more likely than smear-positive specimens to generate a non-actionable MTBDRplus (23% [133/559] versus 4% [15/381]) or MTBDRsl (39% [220/559] versus 12% [47/381]) result. However, excluding smear-negatives would result in missed rapid diagnoses (e.g., only 49% [264/537] of LPA-diagnosable isoniazid resistance would be detected if smear-negatives were omitted). Testing smear-negatives with a semi-quantitation category ≥ "medium" had a high ratio of actionable-to-non-actionable results (12.8 or a 4-fold improvement versus testing all using MTBDRplus, 4.5 or 3-fold improvement for MTBDRsl), which would still capture 64% (168/264) and 77% (34/44) of LPA-detectable smear-negative resistance, respectively. Use of CTmins permitted optimization of this ratio with higher specificity for non-actionable results but decreased resistance detected. Xpert quantitative information permits identification of a smear-negative subset in whom the payoffs of the ratio of actionable-to-non-actionable LPA results with missed resistance may prove acceptable to laboratories, depending on context. Our findings permit the rational expansion of direct DST to certain smear-negative sputum specimens.

Resource implications of the latent tuberculosis cascade of care: a time and motion study in five countries.

BACKGROUND: The End TB Strategy calls for global scale-up of preventive treatment for latent tuberculosis infection (LTBI), but little information is available about the associated human resource requirements. Our study aimed to quantify the healthcare worker (HCW) time needed to perform the tasks associated with each step along the LTBI cascade of care for household contacts of TB patients. METHODS: We conducted a time and motion (TAM) study between January 2018 and March 2019, in which consenting HCWs were observed throughout a typical workday. The precise time spent was recorded in pre-specified categories of work activities for each step along the cascade. A linear mixed model was fit to estimate the time at each step. RESULTS: A total of 173 HCWs in Benin, Canada, Ghana, Indonesia, and Vietnam participated. The greatest amount of time was spent for the medical evaluation (median: 11 min; IQR: 6-16), while the least time was spent on reading a tuberculin skin test (TST) (median: 4 min; IQR: 2-9). The greatest variability was seen in the time spent for each medical evaluation, while TST placement and reading showed the least variability. The total time required to complete all steps along the LTBI cascade, from identification of household contacts (HHC) through to treatment initiation ranged from 1.8 h per index TB patient in Vietnam to 5.2 h in Ghana. CONCLUSIONS: Our findings suggest that the time requirements are very modest to perform each step in the latent TB cascade of care, but to achieve full identification and management of all household contacts will require additional human resources in many settings.

Biaxial sensing suture breakage warning system for robotic surgery.

The number of procedures performed with robotic surgery may exceed one million globally in 2018. The continual lack of haptic feedback, however, forces surgeons to rely on visual cues in order to avoid breaking sutures due to excessive applied force. To mitigate this problem, the authors developed and validated a novel grasper-integrated system with biaxial shear sensing and haptic feedback to warn the operator prior to anticipated suture breakage. Furthermore, the design enables facile suture manipulation without a degradation in efficacy, as determined via measured tightness of resulting suture knots. Biaxial shear sensors were integrated with a da Vinci robotic surgical system. Novice subjects (n = 17) were instructed to tighten 10 knots, five times with the Haptic Feedback System (HFS) enabled, five times with the system disabled. Seven suture failures occurred in trials with HFS enabled while seventeen occurred in trials without feedback. The biaxial shear sensing system reduced the incidence of suture failure by 59% (p = 0.0371). It also resulted in 25% lower average applied force in comparison to trials without feedback (p = 0.00034), which is relevant because average force was observed to play a role in suture breakage (p = 0.03925). An observed 55% decrease in standard deviation of knot quality when using the HFS also indicates an improvement in consistency when using the feedback system. These results suggest this system may improve outcomes related to knot tying tasks in robotic surgery and reduce instances of suture failure while not degrading the quality of knots produced.

Photocatalytic Properties of Plasma-Synthesized Aluminum-Doped Zinc Oxide Nanopowder.

Nano-sized aluminum-doped zinc oxide (AZO) powder was synthesized by a dc thermal plasma process using aluminum nitrate and zinc nitrate as the precursors. The injected precursors were vaporized in the plasma flame followed by vapor-phase reaction and subsequent quenching of the vaporized precursors produced nanosized AZO. XRD results indicate the presence of wurtzite structure without any alumina peaks and SEM micrographs revealed spherical particles. The nanosized AZO would make an excellent material for use as photocatalyst due to high surface to volume ratio. The photocatalytic properties of AZO nanopowder were investigated using the degradation of methylene blue under ultra-violet irradiation. The effects of various parameters, such as catalyst amount, the presence of oxidant, temperature, bubbling of O2 gas, pH, specific surface area, oxygen vacancies, and initial concentration, were studied. The optical study showed that doping leads to a red-shift in band gap. Furthermore, the AZO nanoparticles exhibited superior photocatalytic activity compared with ZnO. The improvement was ascribed to an increase in specific surface area and oxygen vacancies. Kinetic analyses indicated that the photodegradation of methylene blue followed a pseudo-first order kinetic model based on the Langmuir-Hinshelwood (L-H) mechanism.

Devising negative pressure within intercuff space reduces microaspiration.

BACKGROUND: Microaspiration past the tracheal tube cuffs causes ventilator-associated pneumonia. The objective of the current study was to evaluate whether creating negative pressure between the tracheal double cuffs could block the fluid passage past the tracheal tube cuffs. METHODS: A new negative pressure system was devised between the double cuffs through a suction hole in the intercuff space. Blue-dyed water was instilled above the cuff at negative suction pressures of - 54, - 68, - 82, - 95, - 109, - 122, and - 136 cmH2O, and the volume leaked was measured in an underlying water trap after 10 min. Leakage tests were also performed during positive pressure ventilation, and using higher-viscosity materials. The actual negative pressures delivered at the hole of double cuffs were obtained by placing microcatheter tip between the intercuff space and the artificial trachea. RESULTS: No leakage occurred past the double cuff at - 136 cmH2O suction pressure at all tracheal tube cuff pressures. The volume leaked decreased significantly as suction pressure increased. When connected to a mechanical ventilator, no leakage was found at - 54 cmH2suction pressure. Volume of the higher-viscosity materials (dynamic viscosity of 63-108 cP and 370-430 cP) leaked was small compared to that of normal saline (0.9-1.1 cP). The pressures measured in the intercuff space corresponded to 3.8-5.9% of those applied. CONCLUSIONS: A new prototype double cuff with negative pressure in the intercuff space completely prevented water leakage. The negative pressure transmitted to the tracheal inner wall was a small percentage of that applied.

Effect of smoking status on progression-free and overall survival in non-small cell lung cancer patients receiving erlotinib or gefitinib: a meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib or gefitinib are indicated for the treatment of non-small cell lung cancer (NSCLC). EGFR tyrosine kinase domain mutations have been reported to be associated with EGFR-TKI response in patients with NSCLC. Certain patient subgroups in which EGFR somatic mutations are more frequently observed are thought to derive more clinical benefit from EGFR-TKI therapy. We performed a systematic review and meta-analysis to summarize the evidence regarding the association of smoking status with overall survival (OS) and progression-free survival (PFS) in patients with NSCLC receiving EGFR-TKI therapy with erlotinib or gefitinib. METHODS: Eligible studies were selected by two independent reviewers using the inclusion and exclusion criteria predefined in the protocol. Eligible studies included those evaluating the association of smoking status with OS and PFS in patients with NSCLC receiving erlotinib or gefitinib. Non-clinical studies, case reports, non-peer-reviewed abstracts and non-relevant studies were excluded. RESULTS AND DISCUSSION: Data on OS and PFS in patients with NSCLC treated with EGFR-TKIs were available in nine and ten trials, respectively. The OS and PFS from both the treatment and control groups were not significantly different between never smokers and former or current smokers (OS: odds ratio [OR], 0·80; 95% confidence interval [CI], 0·63-1·09; PFS: OR, 0·75; 95% CI, 0·49-1·14), respectively. However, in comparison within each smoking group, EGFR-TKI treatment led to more favourable OS and PFS in never smokers (OS: OR, 0·55; 95% CI, 0·42-0·73; PFS: OR, 0·43; 95% CI, 0·33-0·54), compared with former or current smokers (OS: OR, 0·89; 95% CI, 0·80-0·97; PFS: OR, 0·73; 95% CI, 0·62-0·85). WHAT IS NEW AND CONCLUSION: Among patients with NSCLC receiving EGFR-TKI therapy with erlotinib or gefitinib, never smokers appear to show longer OS and PFS as compared to former or current smokers. However, this is based on indirect comparisons and more robust larger head-to-head trials are required for more robust inferences.

Phase III trial of concurrent thoracic radiotherapy with either first- or third-cycle chemotherapy for limited-disease small-cell lung cancer.

BACKGROUND: We compared late thoracic radiotherapy (TRT) with early TRT in the treatment of limited-disease small-cell lung cancer (LD-SCLC). PATIENTS AND METHODS: Patients with LD-SCLC received four cycles of etoposide plus cisplatin every 21 days. Patients were randomly assigned to receive either TRT administered concurrently with the first cycle (early TRT) or the third cycle (late TRT) of chemotherapy. The primary end point was complete response rate. RESULTS: Two hundred twenty-two patients were randomly assigned.Late TRT was not inferior to early TRT in terms of the complete response rate (early v late; 36.0% v 38.0%). Other efficacy measures including overall survival [median, 24.1 v 26.8 months;hazard ratio (HR) 0.93; 95% CI = 0.67­1.29] and progression free survival (median, 12.4 v 11.2 months; HR 1.09; 95%CI = 0.80­1.48) were not different between two arms. No statistical difference was noted in the pattern of treatment failures.However, neutropenic fever occurred more commonly in the early TRT arm than the late TRT arm (21.6% v 10.2%; P = 0.02) [corrected]. CONCLUSION: In LD-SCLC treatment, TRT starting in the third cycle of chemotherapy seemed to be noninferior to early TRT, and had a more favorable profile with regard to neutropenic fever.

IL-1ß and IL-6 activate inflammatory responses of astrocytes against Naegleria fowleri infection via the modulation of MAPKs and AP-1.

Naegleria fowleri, a free-living amoeba, has been found in diverse habitats throughout the world. It causes primary amoebic meningoencephalitis in children and young adults. The amoeba attaches to nasal mucosa, migrates along olfactory nerves and enters the brain. Astrocytes are involved in the defence against infection and produce inflammatory responses. In this study, we focus on the mechanism of immune responses in astrocytes. We showed, using RNase protection assay, RT-PCR and ELISA in an in vitro culture system, that N. fowleri lysates induce interleukin-1beta (IL-1ß) and IL-6 expression of astrocytes. In addition, cytokine levels of astrocytes gradually decreased due to extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 inhibitors. To determine the transcription factor, we used transcription inhibitor (AP-1 inhibitor), which downregulated IL-1ß and IL-6 expression. These results show that AP-1 is related to IL-1ß and IL-6 production. N. fowleri-mediated IL-1ß and IL-6 expression requires ERK, JNK and p38 mitogen-activated protein kinases (MAPKs) activation in astrocytes. These findings show that N. fowleri-stimulated astrocytes in an in vitro culture system lead to AP-1 activation and the subsequent expressions of IL-1ß and IL-6, which are dependent on ERK, JNK and p38 MAPKs activation. These results may imply that proinflammatory cytokines have important roles in inflammatory responses to N. fowleri infection.

A comparison of inflammatory mediator expression between palmoplantar pustulosis and pompholyx.

BACKGROUND: Both palmoplantar pustulosis (PPP) and pompholyx are clinically characterized by acute eruptions of vesicles or pustules on the palms or soles. OBJECTIVES: This study aims to compare the expression of certain inflammatory mediator genes and proteins between patients with PPP and pompholyx using skin tissue samples. METHODS: Skin biopsies obtained from lesional skin from patients with PPP (n = 7) and pompholyx (n = 5) were analysed by quantitative RT-PCR to measure the mRNA levels of nine genes, including IL-4, IL-8, IL-9, IL-17, IL-22, IFN-γ, CCL-20, granzyme and perforin. For immunohistochemical analysis, 34 paraffin-embedded skin specimens (PPP, n = 22; pompholyx, n = 12) were stained with anti-IL-8, IL-17A, IL-22 and granzyme B antibodies. RESULTS: Of genes analysed, IL-8 and IL-17A mRNA expression levels were significantly higher in the PPP group than the pompholyx group (P = 0.012 in both), whereas the mRNA expression of granzyme B was significantly higher in pompholyx when compared with PPP (P = 0.004). Regarding the IL-17A immunohistochemical staining, tissue from the PPP lesions contained significantly more IL-17A(+) cells in both the epidermis and papillary dermis when compared with pompholyx (P < 0.001 and P = 0.019 respectively). Moreover, the intensity of the IL-8 immunoreactivity was also greater in the PPP skin lesions than the pompholyx tissue (P < 0.001). CONCLUSIONS: IL-8 and IL-17A, both are increased in PPP tissue, may represent important immunologic mediators that help to differentiate this clinical entity from pompholyx. This study may provide useful clues in distinguishing PPP from pompholyx, as well as helping to understand the pathogeneses of these two diseases.

Cost to perform door-to-door universal sputum screening for TB in a high-burden community.

BACKGROUND: Population-based active case-finding (ACF) identifies people with TB in communities but can be costly. METHODS: We conducted an empiric costing study within a door-to-door household ACF campaign in an urban community in Uganda, where all adults, regardless of symptoms, were screened by sputum Xpert Ultra testing. We used a combination of direct observation and self-reported logs to estimate staffing requirements. Study budgets were reviewed to collect costs of overheads, equipment, and consumables. Our primary outcome was the cost per person diagnosed with TB. RESULTS: Over a 28-week period, three teams of two people collected sputum from 11,341 adults, of whom 48 (0.4%) tested positive for TB. Screening 1,000 adults required 258 person-hours of effort at a cost of US$35,000, 70% of which was for GeneXpert cartridges. The estimated cost per person screened was $36 (95% uncertainty range [95% UR] 34­38), and the cost per person diagnosed with Xpert-positive TB was $8,400 (95% UR 8,000­8,900). The prevalence of TB in the underlying community was the primary modifiable determinant of the cost per person diagnosed. CONCLUSION: Door-to-door screening can be feasibly performed at scale, but will require effective triage and identification of high-prevalence populations to be affordable and cost-effective.

Understanding patient-level costs of weekly isoniazid-rifapentine (3HP) among people living with HIV in Uganda.

BACKGROUND: Twelve weeks of weekly isoniazid and rifapentine (3HP) prevents TB disease among people with HIV (PWH), but the costs to people of taking TB preventive treatment is not well described.METHODS: We surveyed PWH who initiated 3HP at a large urban HIV/AIDS clinic in Kampala, Uganda, as part of a larger trial. We estimated the cost of one 3HP visit from the patient perspective, including both out-of-pocket costs and estimated lost wages. Costs were reported in 2021 Ugandan shillings (UGX) and US dollars (USD; USD1 = UGX3,587)RESULTS: The survey included 1,655 PWH. The median participant cost of one clinic visit was UGX19,200 (USD5.36), or 38.5% of the median weekly income. Per visit, the cost of transportation was the largest component (median: UGX10,000/USD2.79), followed by lost income (median: UGX4,200/USD1.16) and food (median: UGX2,000/USD0.56). Men reported greater income loss than women (median: UGX6,400/USD1.79 vs. UGX3,300/USD0.93), and participants who lived further than a 30-minute drive to the clinic had higher transportation costs than others (median: UGX14,000/USD3.90 vs. UGX8,000/USD2.23).CONCLUSION: Patient-level costs to receive 3HP accounted for over one-third of weekly income. Patient-centered approaches to averting or defraying these costs are needed.

Intracellular lipid accumulation inhibitory effect of Weissella koreensis OK1-6 isolated from Kimchi on differentiating adipocyte.

AIMS: To investigate the intracellular lipid accumulation inhibitory effect of spent culture medium extract and the cytoplasmic fraction of Weissella koreensis OK1-6 cells isolated from kimchi in differentiating 3T3-L1 cells. METHODS AND RESULTS: Differentiating 3T3-L1 cells were treated with either cytoplasmic fraction of W. koreensis OK1-6 cells or its spent media for 4 days. Both the spent culture medium extract and cytoplasmic fraction of W. koreensis OK1-6 cells significantly decreased the triglyceride concentration and intracellular lipid accumulation in the treated groups compared with the control group. The mRNA expression levels of C/EBP-α, one of the major transcriptional factors involved in adipocyte differentiation, were significantly less expressed in 3T3-L1 cells treated with the spent medium and cytoplasmic fraction. The expressions of aP2, fatty acid synthase (FAS) and SREBP1 genes were also decreased significantly. CONCLUSIONS: These results suggested that W. koreensis OK1-6 could play a crucial role in preventing intracellular lipid accumulation by down-regulating the expression of adipocyte-specific genes C/EBPα, aP2, SREBP1 and FAS. SIGNIFICANCE AND IMPACT OF THE STUDY: These results may contribute to nutraceutical and food industries in developing probiotic-based therapies for the treatment and prevention of obesity.

Bovine spongiform encephalopathy surveillance in the Republic of Korea.

National surveillance for bovine spongiform encephalopathy (BSE) began in the Republic of Korea (ROK) in 1996. Surveillance programmes changed overtime to comply with the guidelines of the World Organisation for Animal Health (OIE). Bovine spongiform encephalopathy was designated as a notifiable disease in 1997. From July 2008, the BSE surveillance programme was intensified to test cattle in designated high-risk populations more effectively. New measures included the compulsory testing of all non-ambulatory cattle at abattoirs, and encouraging the testing of all dead cattle examined and recorded under the Mutual Aid Insurance Scheme (fallen stock). In addition, there was a vigorous search for animals suspected of being clinically infected. As a result, a total of 426,919 OIE points were achieved over a period of seven consecutive years to the end of October 2009. This enabled the submission of a successful application to the OIE in 2010 for recognition of the ROK's BSE disease status as being one of controlled risk, in accordance with Chapter 11.5. of the OIE Terrestrial Animal Health Code.

Is childhood physical abuse associated with anxiety disorders among adults?

Several studies have examined the association between childhood physical abuse (CPA) and anxiety disorders with inconsistent results. In order to help clarify this relationship, we investigated the association between CPA and current anxiety disorders while controlling for the following groups of factors: (1) demographics; (2) family background; (3) current socioeconomic status (SES); (4) current stressors; and (5) current mood disorders. Data from the 2005 Canadian Community Health Survey were analyzed. The sample included 12,481 respondents from the Canadian provinces of Manitoba and Saskatchewan. The regional-level response rate was 84%. Fully 7.3% (n = 964) of respondents reported they had been physically abused as a child or adolescent by someone close to them and 4.4% (n = 540) reported they had been diagnosed with an anxiety disorder by a health professional. A significant association between CPA and anxiety disorders was found when controlling for demographic factors, family background, current SES and stressors (OR = 1.61; 95% CI = 1.25, 2.08). The odds of anxiety disorders declined to non-significance when further statistical adjustments were made for current mood disorders. The findings of this research suggest that the relationship between CPA and anxiety may be largely explained by co-morbid mood disorders.

Comparative cost and performance of light-emitting diode microscopy in HIV-tuberculosis-co-infected patients.

Light-emitting diode (LED) microscopy has recently been endorsed by the World Health Organization (WHO). However, it is unclear whether LED is as accurate and cost-effective as Ziehl-Neelsen (ZN) microscopy or mercury vapour fluorescence microscopy (MVFM) in tuberculosis (TB)-HIV-co-infected subjects. Direct and concentrated sputum smears from TB suspects were evaluated using combinations of LED microscopy, ZN microscopy and MVFM. Median reading time per slide was recorded and a cost analysis performed. Mycobacterial culture served as the reference standard. 647 sputum samples were obtained from 354 patients (88 (29.8%) were HIV-infected and 161 (26%) were culture-positive for Mycobacterium tuberculosis). Although overall sensitivity of LED compared with ZN microscopy or MVFM was similar, sensitivity of all three modalities was lower in HIV-infected patients. In the HIV-infected group, the sensitivity of LED microscopy was higher than ZN microscopy using samples that were not concentrated (46 versus 39%; p = 0.25), and better than MVFM using concentrated samples (56 versus 44; p = 0.5). A similar trend was seen in the CD4 count <200 cells · mL(-1) subgroup. Median (interquartile range) reading time was quicker with LED compared with ZN microscopy (1.8 (1.7-1.9) versus 2.5 (2.2-2.7) min; p ≤ 0.001). Average cost per slide read was less for LED microscopy (US$1.63) compared with ZN microscopy (US$2.10). Among HIV-TB-co-infected patients, LED microscopy was cheaper and performed as well as ZN microscopy or MVFM independent of the staining (ZN or auramine O) or processing methods used.

Hair greying is associated with active hair growth.

BACKGROUND: Hair greying is an obvious sign of ageing in humans. White (nonpigmented) hair is thicker than black (pigmented) hair. The growth rate of white hair is also significantly higher than that of black hair. However, the mechanism underlying this is largely unknown. OBJECTIVES: To examine the association between hair greying and hair growth patterns by evaluating expression of the genes or proteins related to hair growth in white and black hairs. METHODS: Morphological characteristics were observed in eyebrow and scalp hairs. The differential expression of genes was analysed in black and white hairs from human scalp by a microarray analysis. Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry for genes and proteins related to hair growth were performed in black and white hairs. RESULTS: Keratin and keratin-associated protein (KRTAP) genes in white hair were upregulated at least two-fold in comparison with black hair in a microarray analysis. Upregulation of selected keratin genes and KRTAP4 isoform genes in white hair was validated by RT-PCR. Immunoreactivity for KRT6, KRT14/16 and KRT25 was increased in the hair follicle of white hair compared with black hair. Gene expression of fibroblast growth factor 5 (FGF5) was downregulated in white hair compared with black hair. However, gene expression of FGF7 was upregulated in white hair compared with black hair. CONCLUSIONS: Expression of genes and proteins associated with active hair growth is upregulated in white (nonpigmented) hair compared with black (pigmented) hair. These results suggest that hair greying is associated with active hair growth.

Effects of immunization with the rNfa1 protein on experimental Naegleria fowleri-PAM mice.

Free-living Naegleria fowleri causes primary amoebic meningoencephalitis (PAM) in humans and animals. To examine the effect of immunization with Nfa1 protein on experimental murine PAM because of N. fowleri, BALB/c mice were intra-peritoneally or intra-nasally immunized with a recombinant Nfa1 protein. We analysed Nfa1-specific antibody and cytokine induction, and the mean survival time of infected mice. Mice immunized intra-peritoneally or intra-nasally with rNfa1 protein developed specific IgG, IgA and IgE antibodies; the IgG response was dominated by IgG1, followed by IgG2b, IgG2a and IgG3. High levels of the Th1 cytokine, IFN-γ, and the regulatory cytokine, IL-10, were also induced. The mean survival time of mice immunized intra-peritoneally with rNfa1 protein was prolonged compared with controls, (25.0 and 15.5 days, respectively). Similarly, the mean survival time of mice immunized intra-nasally with rNfa1 protein was 24.7 days, compared with 15.0 days for controls.

Determining the value of TB active case-finding: current evidence and methodological considerations.

Active case-finding (ACF) is an important component of the End TB Strategy. However, ACF is resource-intensive, and the economics of ACF are not well-understood. Data on the costs of ACF are limited, with little consistency in the units and methods used to estimate and report costs. Mathematical models to forecast the long-term effects of ACF require empirical measurements of the yield, timing and costs of case detection. Pragmatic trials offer an opportunity to assess the cost-effectiveness of ACF interventions within a 'real-world´ context. However, such analyses generally require early introduction of economic evaluations to enable prospective data collection on resource requirements. Closing the global case-detection gap will require substantial additional resources, including continued investment in innovative technologies. Research is essential to the optimal implementation, cost-effectiveness, and affordability of ACF in high-burden settings. To assess the value of ACF, we must prioritize the collection of high-quality data regarding costs and effectiveness, and link those data to analytical models that are adapted to local settings.

Low central venous pressure with milrinone during living donor hepatectomy.

Maintaining a low central venous pressure (CVP) has been frequently used in liver resections to reduce blood loss. However, decreased preload carries potential risks such as hemodynamic instability. We hypothesized that a low CVP with milrinone would provide a better surgical environment and hemodynamic stability during living donor hepatectomy. Thirty-eight healthy adult liver donors were randomized to receive either milrinone (milrinone group, n = 19) or normal saline (control group, n = 19) infusion during liver resection. The surgical field was assessed using a four-point scale. Intraoperative vital signs, blood loss, the use of vasopressors and diuretics and postoperative laboratory data were compared between groups. The milrinone group showed a superior surgical field (p < 0.001) and less blood loss (142 +/- 129 mL vs. 378 +/- 167 mL, p < 0.001). Vital signs were well maintained in both groups but the milrinone group required smaller amounts of vasopressors and less-frequent diuretics to maintain a low CVP. The milrinone group also showed a more rapid recovery pattern after surgery. Milrinone-induced low CVP improves the surgical field with less blood loss during living donor hepatectomy and also has favorable effects on intraoperative hemodynamics and postoperative recovery.