Successful treatment of sino-pulmonary infection & skull base osteomyelitis caused by New Delhi metallo-ß-lactamase-producing Pseudomonas aeruginosa in a renal transplant recipient by using an investigational antibiotic cefepime/zidebactam (WCK 5222).

A case of sino-pulmonary infection with skull base osteomyelitis due to XDR-Pseudomonas aeruginosa in renal transplant recipient was successfully treated with investigational antibiotic, cefepime/zidebactam (WCK 5222). This case highlights challenges in managing XDR-pseudomonal infection where source control was infeasible, antibiotic options were extremely limited and individualized dose adjustments were needed.

Ethylene Elimination Using Activated Carbons Obtained from Baru (Dipteryx alata vog.) Waste and Impregnated with Copper Oxide.

Ethylene is a plant hormone regulator that stimulates chlorophyll loss and promotes softening and aging, resulting in a deterioration and reduction in the post-harvest life of fruit. Commercial activated carbons have been used as ethylene scavengers during the storage and transportation of a great variety of agricultural commodities. In this work, the effect of the incorporation of copper oxide over activated carbons obtained from baru waste was assessed. Samples were characterized by X-ray diffraction (XRD), N2 adsorption-desorption at -196 °C, field-emission scanning electron microscopy (FESEM) coupled with energy-dispersive X-ray spectroscopy (EDS), and infrared (IR) spectroscopy. The results showed that the amount of ethylene removed using activated carbon obtained from baru waste and impregnated with copper oxide (1667 µg g-1) was significantly increased in comparison to the raw activated carbon (1111 µg g-1). In addition, carbon impregnated with copper oxide exhibited better adsorption performance at a low ethylene concentration. Activated carbons produced from baru waste are promising candidates to be used as adsorbents in the elimination of ethylene during the storage and transportation of agricultural commodities at a lower cost.

Target product profiles for diagnosis of sepsis: Proposing a new approach for diagnostic innovation.

Background & objectives: Sepsis, including neonatal sepsis, remains a prevalent cause of morbidity and mortality in low- and middle-income countries such as India, representing 85 per cent of all sepsis-related deaths globally. Early diagnosis and timely initiation of treatment is challenging due to non-specific clinical manifestations and non-availability of rapid diagnostic tests. There is an urgent need for affordable diagnostics with fast turnaround time catering to the needs of end-users. Target product profiles (TPPs) have been found instrumental in developing 'fit-for-use' diagnostics, thus reducing the time taken to facilitate development and improving diagnosis. Hitherto, no such guidance or criteria has been defined for rapid diagnostics for sepsis/neonatal sepsis. We propose an innovative approach for developing the diagnostics for sepsis screening and diagnosis which can be utilized by diagnostic developers in the country. Methods: Thr@ee-round Delphi method, including two online surveys and one virtual consultation, was adopted to define criteria for minimum and optimum attributes of TPPs and build consensus on characteristics. Expert panel (n=23) included infectious disease physicians, public health specialists, clinical microbiologists, virologists, researchers/scientists and technology experts/innovators. Results: We present a three-component product profile for sepsis diagnosis, (i) screening with high sensitivity, (ii) detection of aetiological agent, and (iii) profiling of antimicrobial susceptibility/resistance, in adults and neonates with an option of testing different considerations. An agreement of >75 per cent was achieved for all TPP characteristics by Delphi. These TPPs are tailored to the Indian healthcare settings and can also be extrapolated to other resource-constraint and high-disease burden settings. Interpretation & conclusions: Diagnostics developed using these TPPs will facilitate utilization of invested resources leading to development of the products that have potential to ease the economic burden on patient and save lives.

Daily consumption of ultra-processed foods and cardiometabolic risk factors in children aged 7 to 10 years in Northeast Brazil.

Background: Ultra-processed foods (UPFs) consumption is associated with pediatric overweight and obesity. Aim: To evaluate the UPFs consumption in children classified either as eutrophic or with excess weight (overweight and obesity). It was also described the fasting plasma glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) and the correlation between UPFs consumption and cardiometabolic risk factors. Methods: A total of 139 children aged 7-10years of both sexes, living in Northeast Brazil were classified as eutrophic (n = 65) or excess weight (n = 62). Waist circumference (WC), percentage of body fatness (% BF), fat-free-mass and fat mass were evaluated. Fasting blood sample were collected for biochemical analysis. Food consumption was classified according to the degree of processing. Results: Children with excess weight had a reduction in plasma HDL concentration (45.00; IQR:36.00-54.50 mg/dL vs. 40.00; IQR:35.75-45.25 mg/dL; p = 0.021) and an increase in blood glucose (82.00; IQR:79.00-86.00 mg/dL vs. 86.00; IQR:81.00-90.00 mg/dL; p < 0.001) and TG (64.00; IQR:45.00-92.50 mg/dL vs. 81.00; IQR:57.50-111.75 mg/dL; p < 0.021) when compared with the eutrophic children. UPFs accounted for 43.43% of the total calories consumed by children. Children with excess weight had higher total energy consumption resulting from consumption of UPFs (714.30 ± 26.32 kcal vs. 848.06 ± 349.46 kcal; p = 0.011). The absolute consumption of the UPFs showed a positive correlation with WC (r = 0.202; p = 0.023) and %BF (r = 0.198; p = 0.026). Conclusion: UPFs consumption was higher for children with excess weight and positively correlated with two cardiometabolic risk factors, suggesting the need for strengthening public policies that discourage the consumption of these foods.

Aspirin-Triggered Resolvin D1 (AT-RvD1) Protects Mouse Skin against UVB-Induced Inflammation and Oxidative Stress.

Intense exposure to UVB radiation incites excessive production of reactive oxygen species (ROS) and inflammation. The resolution of inflammation is an active process orchestrated by a family of lipid molecules that includes AT-RvD1, a specialized proresolving lipid mediator (SPM). AT-RvD1 is derived from omega-3, which presents anti-inflammatory activity and reduces oxidative stress markers. The present work aims to investigate the protective effect of AT-RvD1 on UVB-induced inflammation and oxidative stress in hairless mice. Animals were first treated with 30, 100, and 300 pg/animal AT-RvD1 (i.v.) and then exposed to UVB (4.14 J/cm2). The results showed that 300 pg/animal of AT-RvD1 could restrict skin edema, neutrophil and mast cell infiltration, COX-2 mRNA expression, cytokine release, and MMP-9 activity and restore skin antioxidant capacity as per FRAP and ABTS assays and control O2•- production, lipoperoxidation, epidermal thickening, and sunburn cells development. AT-RvD1 could reverse the UVB-induced downregulation of Nrf2 and its downstream targets GSH, catalase, and NOQ-1. Our results suggest that by upregulating the Nrf2 pathway, AT-RvD1 promotes the expression of ARE genes, restoring the skin's natural antioxidant defense against UVB exposition to avoid oxidative stress, inflammation, and tissue damage.

Bedaquiline Drug Resistance Emergence Assessment in Multidrug-Resistant Tuberculosis (MDR-TB): a 5-Year Prospective In Vitro Surveillance Study of Bedaquiline and Other Second-Line Drug Susceptibility Testing in MDR-TB Isolates.

Bedaquiline Drug Resistance Emergence Assessment in Multidrug-resistant tuberculosis (MDR-TB) (DREAM) was a 5-year (2015 to 2019) phenotypic drug resistance surveillance study across 11 countries. DREAM assessed the susceptibility of 5,036 MDR-TB isolates of bedaquiline treatment-naive patients to bedaquiline and other antituberculosis drugs by the 7H9 broth microdilution (BMD) and 7H10/7H11 agar dilution (AD) MIC methods. Bedaquiline AD MIC quality control (QC) range for the H37Rv reference strain was unchanged, but the BMD MIC QC range (0.015 to 0.12 µg/ml) was adjusted compared with ranges from a multilaboratory, multicountry reproducibility study conforming to Clinical and Laboratory Standards Institute Tier-2 criteria. Epidemiological cutoff values of 0.12 µg/ml by BMD and 0.25 µg/ml by AD were consistent with previous bedaquiline breakpoints. An area of technical uncertainty or intermediate category was set at 0.25 µg/ml and 0.5 µg/ml for BMD and AD, respectively. When applied to the 5,036 MDR-TB isolates, bedaquiline-susceptible, -intermediate, and -resistant rates were 97.9%, 1.5%, and 0.6%, respectively, for BMD and 98.8%, 0.8%, and 0.4% for AD. Resistance rates were the following: 35.1% ofloxacin, 34.2% levofloxacin, 33.3% moxifloxacin, 1.5% linezolid, and 2% clofazimine. Phenotypic cross-resistance between bedaquiline and clofazimine was 0.4% in MDR-TB and 1% in pre-extensively drug-resistant (pre-XDR-TB)/XDR-TB populations. Coresistance to bedaquiline and linezolid and clofazimine and linezolid were 0.1% and 0.3%, respectively, in MDR-TB and 0.2% and 0.4%, respectively, in pre-XDR-TB/XDR-TB populations. Resistance rates to bedaquiline appear to be low in the bedaquiline-treatment-naive population. No treatment-limiting patterns for cross-resistance and coresistance have been identified with key TB drugs to date.

Salvaging lives in carbapenem-resistant Gram-negative osteoarticular and soft tissue infections: early compromises save lives.

PURPOSE: Incidence of carbapenem-resistant Gram-negative infections has risen alarmingly all across the globe, both in developed and developing countries alike. The purpose of this study was to assess whether challenges of life-threatening infections with very high resistance pattern can be successfully addressed by a modified approach. METHODS: This is a retrospective study of 26 patients with osteoarticular and soft tissue infections with carbapenem-resistant Gram-negative bacilli treated between 2001 and 2017 with at least two year follow-up after stopping antibiotics. All were treated by a multispecialty team approach with primary aim of "source control at the earliest and avoiding recurrence at all cost". The protocol involved opting for early compromises especially in at "risk individuals", such as resorting to early amputations, especially if salvage meant multiple bony and soft tissue reconstructive procedures, explanation of prosthesis than staged revision, avoiding internal fixations, opting for shortest possible time in external fixators with reshaping and telescoping bone ends to get bony stability and increase surface area even if it meant compromising length. RESULTS: There were five amputations, two excision arthroplasty of hip, many minor but acceptable malunions and shortening. However, lives of 24/26 patients could be salvaged, much better than most of the published data. The two patients who died had peri-prosthetic joint infection after total hip arthroplasty and presented very late in sepsis and died within days of explantation. Infection remission could be achieved in remaining patients. CONCLUSION: These "risk to life" cases can be successfully treated by lowering the aims and expectations from "excellent function to salvage of life and infection remission". Therein lies the "success" in these complex high-risk cases.

Food consumption habits, gestational age and birth weight are predictive for children with excess weight: An analysis based on artificial neural network.

The relationship between body weight gain and the onset of obesity is linked to environmental and behavioral factors, and may be dependent on biological predisposing. Artificial neural networks are useful predictive tools in the field of artificial intelligence, and can be used to identify risk factors related to obesity. The aim of this study is to establish, based on artificial neural networks, a predictive model for overweight/obesity in children based on the recognition and selection of patterns associated with birth weight, gestational age, height deficit, food consumption, and the physical activity level, TV time and family context. Sample consisted of 149 children (72 = eutrophic and 77 = overweight/obese). Collected data consisted of anthropometry and demographic characteristics, gestational age, birth weight, food consumption, physical activity level, TV time and family context. The gestational age, daily caloric intake and birth weight were the main determinants of the later appearance of overweight and obesity. In addition, the family context linked to socioeconomic factors, such as the number of residents in the household, had a great impact on excess weight. The physical activity level was the least important variable. Modifiable risk factors, such as the inadequate food consumption, and non-modifiable factors such as gestational age were the main determinants for overweight/obesity in children. Our data indicate that, combating excess weight should also be carried out from a social and preventive perspective during critical periods of development, such as pregnancy, lactation and early childhood, to reach a more effective strategy to combat obesity and its complications in childhood and adult life.

Mobile thrombus of the abdominal aorta: a narrative review.

A primary aortic mural thrombus (PAMT) is defined as a thrombus attached to the aortic wall in the absence of any atherosclerotic or aneurysmal disease of the aorta or any cardiac source of embolus. It is a rare entity that has high morbidity and mortality. There is no consensus on the ideal treatment of PAMT. The objective of this paper is to review the possibilities for treatment of mobile abdominal aortic mural thrombus. Endovascular therapy and open surgery appear to be the best options for treatment of mobile abdominal aortic mural thrombus. Thus, in patients with favorable anatomy, endovascular therapy is probably the treatment choice, while in those with unfavorable anatomy, open surgery is probably the best option for treatment of a mobile abdominal aortic thrombus. It is important to emphasize that anticoagulation alone can be used as a non-aggressive option and, if this fails, endovascular or surgical methods can then be employed.

O trombo mural aórtico primário é definido como um trombo aderido à parede aórtica na ausência de doença aterosclerótica e/ou aneurismática ou de fonte cardíaca de êmbolo. Trata-se de uma doença rara, porém causadora de alta morbimortalidade, e não há consenso acerca do seu tratamento. Este estudo objetivou revisar as possibilidades na presença de componente móvel. A terapia endovascular e a cirurgia aberta parecem ser as melhores opções, sendo a abordagem endovascular o tratamento de escolha para pacientes com anatomia favorável e a cirurgia aberta o tratamento de escolha para pacientes com anatomia desfavorável. No entanto, a anticoagulação sistêmica apresenta-se como método não invasivo para pacientes com alto risco cirúrgico e como possibilidade terapêutica na falha ou indisponibilidade de abordagem cirúrgica.

Immune Modulation and Cytomegalovirus Reactivation in Sepsis-induced Immunosuppression: A Pilot Study.

INTRODUCTION: Sepsis is a life-threatening condition caused due to dysregulated immune response to an infection and progressive immunosuppression. Reactivation of cytomegalovirus (CMV) occurs frequently in sepsis and is found associated with adverse outcomes. The study objective was to evaluate the association between incidence of CMV reactivation and immune alteration in sepsis-induced immunosuppression in patients with prolonged sepsis. PATIENTS AND METHODS: Patients admitted to intensive care unit (ICU), with severe sepsis and CMV immunoglobulin G (IgG) seropositivity, were prospectively enrolled. Other manifest immune suppression causes were excluded. Samples were collected on enrolment and further once a week until day 21 or death/discharge. CMV viral load was quantified using qPCR. Lymphocyte subset analysis (CD3+, CD4+, CD8+, CD19+, CD16+/CD56+, and CD25+CD127- regulatory T cells), human leukocyte antigen-DR isotype (HLA-DR) expression on monocytes, programmed death-1 (PD-1) expression on T lymphocytes, and proinflammatory (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ)), anti-inflammatory cytokines levels (IL-2, IL-4, and IL-10) were analyzed by flow cytometry as markers for immunosuppression. RESULTS: A total of 25 CMV IgG-positive patients and 11 healthy controls were included. CMV reactivation occurred in 20 patients. Patients with CMV reactivation had T-cell lymphopenia. PD-1 expression on CD4+ and CD8+ T cells was markedly elevated (p <0.02) in CMV-reactivated patients compared to nonreactivated patients. HLA-DR expression was significantly low on monocytes in all septic patients (p <0.01) compared to healthy controls. IL-6 levels showed elevation at day 7, whereas IL-10 was found to be significantly higher from day 0 in CMV-reactivated group. CONCLUSION: Our study concluded that immune suppression markers and cytokine levels in patients with severe sepsis were found to be significantly associated with the incidence of CMV reactivation. HOW TO CITE THIS ARTICLE: Lambe G, Mansukhani D, Khodaiji S, Shetty A, Rodrigues C, Kapadia F. Immune Modulation and Cytomegalovirus Reactivation in Sepsis-induced Immunosuppression: A Pilot Study. Indian J Crit Care Med 2022;26(1):53-61.

A prospective multicentre diagnostic accuracy study for the Truenat tuberculosis assays.

BACKGROUND: Bringing reliable and accurate tuberculosis (TB) diagnosis closer to patients is a key priority for global TB control. Molbio Diagnostics have developed the Truenat point-of-care molecular assays for detection of TB and rifampicin (RIF) resistance. METHODS: We conducted a prospective multicentre diagnostic accuracy study at 19 primary healthcare centres and seven reference laboratories in Peru, India, Ethiopia and Papua New Guinea to estimate the diagnostic accuracy of the point-of-care Truenat MTB, MTB Plus and MTB-RIF Dx assays for pulmonary TB using culture and phenotypic drug susceptibility testing as the reference standard, compared with Xpert MTB/RIF or Ultra. RESULTS: Of 1807 enrolled participants with TB signs/symptoms, 24% were culture-positive for Mycobacterium tuberculosis, of which 15% were RIF-resistant. In microscopy centres, the pooled sensitivity of Truenat MTB and Truenat MTB Plus was 73% (95% CI 67-78%) and 80% (95% CI 75-84%), respectively. Among smear-negative specimens, sensitivities were 36% (95% CI 27-47%) and 47% (95% CI 37-58%), respectively. Sensitivity of Truenat MTB-RIF was 84% (95% CI 62-95%). Truenat assays showed high specificity. Head-to-head comparison in the central reference laboratories suggested that the Truenat assays have similar performance to Xpert MTB/RIF. CONCLUSION: We found the performance of Molbio's Truenat MTB, MTB Plus and MTB-RIF Dx assays to be comparable to that of the Xpert MTB/RIF assay. Performing the Truenat tests in primary healthcare centres with very limited infrastructure was feasible. These data supported the development of a World Health Organization policy recommendation of the Molbio assays.

Protection against UVB deleterious skin effects in a mouse model: effect of a topical emulsion containing Cordia verbenacea extract.

Cordia verbenacea DC (Boraginaceae) is a flowering shrub found along the Brazilian Atlantic Forest, Brazilian coast, and low areas of the Amazon. The crude extract of its leaves is widely used in Brazilian folk medicine as an anti-inflammatory, both topically and orally. The aim of this study is to evaluate the activity of C. verbenacea ethanolic leaves extract (CVE) against UVB-triggered cutaneous inflammation and oxidative damage in hairless mice. CVE treatment recovered cutaneous antioxidant capacity demonstrated by scavenging ABTS+ free radical and iron-reducing antioxidant potential evaluated by FRAP. CVE also controlled the following UV-triggered events in the skin: reduced glutathione (GSH) depletion, catalase activity decrease, and superoxide anion (O⋅-) build-up. Furthermore, mice treated with CVE exhibited less inflammation, shown by the reduction in COX-2 expression, TNF-α, IL-1ß, IL-6, edema, and neutrophil infiltration. CVE also regulated epidermal thickening and sunburn cells, reduced dermal mast cells, and preserved collagen integrity. The best results were obtained using 5% CVE-added emulsion. The present data demonstrate that topical administration of CVE presents photochemoprotective activity in a mouse model of UVB inflammation and oxidative stress. Because of the intricate network linking inflammation, oxidative stress, and skin cancer, these results also indicate the importance of further studies elucidating a possible role of C. verbenacea in the prevention of UVB-induced skin cancer and evaluating a potential synergy between CVE and sunscreens in topical products against UVB damaging effects to the skin.

Linezolid resistance in Mycobacterium tuberculosis isolates at a tertiary care centre in Mumbai, India.

Background & objectives: Linezolid (LZD) is increasingly being used in tuberculosis (TB) treatment. However, LZD resistance has already been reported, which is highly alarming, given its critical therapeutic role. This study was aimed to phenotypically and genotypically assess LZD resistance in Mycobacterium tuberculosis (MTB) isolates at a laboratory in a tertiary care centre in Mumbai, India. Methods: A sample of 32 consecutive LZD-resistant MTB isolates identified by liquid culture susceptibility testing was subjected to whole-genome sequencing (WGS) on the Illumina NextSeq platform. Sequences were analyzed using BioNumerics software to predict resistance for 12 antibiotics within 15 min. Results: Sixty eight of the 2179 isolates tested for LZD resistance by MGIT-based susceptibility testing (June 2015 to June 2016) were LZD-resistant. Thirty two consecutive LZD-resistant isolates were analyzed by WGS to screen for known mutations conferring LZD resistance. WGS of 32 phenotypically LZD-resistant isolates showed that C154R in the rplC gene and G2814T in the rrl gene were the major resistance determinants. Interpretation & conclusions: LZD resistance poses an important risk to the success of treatment regimens, especially those designed for resistant isolates; such regimens are extensively used in India. As LZD-containing regimens increase in prominence, it is important to support clinical decision-making with an improved understanding of the common mutations conferring LZD resistance and their frequency in different settings.

Topical Administration of 15-Deoxy-Δ 12,14-Prostaglandin J2 Using a Nonionic Cream: Effect on UVB-Induced Skin Oxidative, Inflammatory, and Histopathological Modifications in Mice.

UVB radiation is certainly one of the most important environmental threats to which we are subjected to. This fact highlights the crucial protective role of the skin. However, the skin itself may not be capable of protecting against UVB depending on irradiation intensity and time of exposition. Sun blockers are used to protect our skin, but they fail to fully protect it against oxidative and inflammatory injuries initiated by UVB. To solve this issue, topical administration of active molecules is an option. 15-Deoxy-Δ 12,14-prostaglandin J2 (15d-PGJ2) is an arachidonic acid-derived lipid with proresolution and anti-inflammatory actions. However, as far as we are aware, there is no evidence of its therapeutic use in a topical formulation to treat the deleterious events initiated by UVB, which was the aim of the present study. We used a nonionic cream to vehiculate 15d-PGJ2 (30, 90, and 300 ng/mouse) (TFcPGJ2) in the skin of hairless mice. UVB increased skin edema, myeloperoxidase activity, metalloproteinase-9 activity, lipid peroxidation, superoxide anion production, gp91phox and COX-2 mRNA expression, cytokine production, sunburn and mast cells, thickening of the epidermis, and collagen degradation. UVB also diminished skin ability to reduce iron and scavenge free radicals, reduced glutathione (GSH), sulfhydryl proteins, and catalase activity. TFcPGJ2 inhibited all these pathological alterations in the skin caused by UVB. No activity was observed with the unloaded topical formulation. The protective outcome of TFcPGJ2 indicates it is a promising therapeutic approach against cutaneous inflammatory and oxidative pathological alterations.

The Interaction of Acute and Chronic Glycemia on the Relationship of Hyperglycemia, Hypoglycemia, and Glucose Variability to Mortality in the Critically Ill.

OBJECTIVES: To determine the relationship between preadmission glycemia, reflected by hemoglobin A1c level, glucose metrics, and mortality in critically ill patients. DESIGN: Retrospective cohort investigation. SETTING: University affiliated adult medical-surgical ICU. PATIENTS: The investigation included 5,567 critically ill patients with four or more blood glucose tests and hemoglobin A1c level admitted between October 11, 2011 and November 30, 2019. The target blood glucose level was 90-120 mg/dL for patients admitted before September 14, 2014 (n = 1,614) and 80-140 mg/dL or 110-160 mg/dL for patients with hemoglobin A1c less than 7% or greater than or equal to 7% (n = 3,953), respectively, subsequently. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were stratified by hemoglobin A1c: less than 6.5.(n = 4,406), 6.5-7.9% (n = 711), and greater than or equal to 8.0% (n = 450). Increasing hemoglobin A1c levels were associated with significant increases in mean glycemia, glucose variability, as measured by coefficient of variation, and hypoglycemia (p for trend < 0.0001, < 0.0001, and 0.0010, respectively). Among patients with hemoglobin A1c less than 6.5%, mortality increased as mean glycemia increased; however, among patients with hemoglobin A1c greater than or equal to 8.0%, the opposite relationship was observed (p for trend < 0.0001 and 0.0027, respectively). Increasing glucose variability was independently associated with increasing mortality only among patients with hemoglobin A1c less than 6.5%. Hypoglycemia was independently associated with higher mortality among patients with hemoglobin A1c less than 6.5% and 6.5-7.9% but not among those with hemoglobin A1c greater than or equal to 8.0%. Mean blood glucose 140-180 and greater than or equal to 180 mg/dL were independently associated with higher mortality among patients with hemoglobin A1c less than 6.5% (p < 0.0001 for each). Among patients with hemoglobin A1c greater than or equal to 8.0% treated in the second era, mean blood glucose greater than or equal to 180 mg/dL was independently associated with decreased risk of mortality (p = 0.0358). CONCLUSIONS: Preadmission glycemia, reflected by hemoglobin A1c obtained at the onset of ICU admission, has a significant effect on the relationship of ICU glycemia to mortality. The different responses to increasing mean glycemia support a personalized approach to glucose control practices in the ICU.

The Lipoxin Receptor/FPR2 Agonist BML-111 Protects Mouse Skin Against Ultraviolet B Radiation.

Excessive exposure to UV, especially UVB, is the most important risk factor for skin cancer and premature skin aging. The identification of the specialized pro-resolving lipid mediators (SPMs) challenged the preexisting paradigm of how inflammation ends. Rather than a passive process, the resolution of inflammation relies on the active production of SPMs, such as Lipoxins (Lx), Maresins, protectins, and Resolvins. LXA4 is an SPM that exerts its action through ALX/FPR2 receptor. Stable ALX/FPR2 agonists are required because SPMs can be quickly metabolized within tissues near the site of formation. BML-111 is a commercially available synthetic ALX/FPR2 receptor agonist with analgesic, antioxidant, and anti-inflammatory properties. Based on that, we aimed to determine the effect of BML-111 in a model of UVB-induced skin inflammation in hairless mice. We demonstrated that BML-111 ameliorates the signs of UVB-induced skin inflammation by reducing neutrophil recruitment and mast cell activation. Reduction of these cells by BML-111 led to lower number of sunburn cells formation, decrease in epidermal thickness, collagen degradation, cytokine production (TNF-α, IL-1ß, IL-6, TGF, and IL-10), and oxidative stress (observed by an increase in total antioxidant capacity and Nrf2 signaling pathway), indicating that BML-111 might be a promising drug to treat skin disorders.

Guidance for Studies Evaluating the Accuracy of Rapid Tuberculosis Drug-Susceptibility Tests.

The development and implementation of rapid molecular diagnostics for tuberculosis (TB) drug-susceptibility testing is critical to inform treatment of patients and to prevent the emergence and spread of resistance. Optimal trial planning for existing tests and those in development will be critical to rapidly gather the evidence necessary to inform World Health Organization review and to support potential policy recommendations. The evidence necessary includes an assessment of the performance for TB and resistance detection as well as an assessment of the operational characteristics of these platforms. The performance assessment should include analytical studies to confirm the limit of detection and assay ability to detect mutations conferring resistance across globally representative strains. The analytical evaluation is typically followed by multisite clinical evaluation studies to confirm diagnostic performance in sites and populations of intended use. This paper summarizes the considerations for the design of these analytical and clinical studies.

Multiplex PCR to detect pAmpC ß-lactamases among enterobacteriaceae at a tertiary care laboratory in Mumbai, India.

Drug-resistance due to AmpC ß-lactamases represents a growing problem worldwide. In this study, a previously collected sample of 108 cefoxitin-resistant clinical isolates was assessed for AmpC ß-lactamase production through routine phenotypic testing and double-disc cefoxitin/cloxcallin (DD-CC), cefoxitin/phenylboronic acid (CDT-PBA) and AmpC disc tests. The same isolates were characterized by a novel multiplex polymerase chain reaction molecular assay to detect the presence of blaACT, blaDHA, blaCIT, blaFOX, blaMIR and blaMOX. By phenotypic analysis, 56%, 55% and 48 % were detected as being AmpC ß-lactamase producers by the CDT-PBA, DD-CC and AmpC disc tests, respectively. By molecular analysis, 57  % were determined to be AmpC ß-lactamase producers, including 34 % blaFOX, 8 % blaCIT and 1.6 % blaDHAas mono-AmpC producers. The production of multiple AmpC molecular types was common, including 30 % with both blaCIT+FOX and 1.6 % each of blaCIT+DHA, blaACT+MIR, blaACT+FOX, blaACT+DHA and blaMIR+FOX. Molecular characterization of AmpC would help detect the prevalence of AmpC ß-lactamase producers, facilitate proper patient management and implement infection control practices.

Few eligible for the newly recommended short course MDR-TB regimen at a large Mumbai private clinic.

BACKGROUND: India has the world's highest tuberculosis burden, and Mumbai is particularly affected by multidrug resistant tuberculosis (MDR-TB). WHO recommends short, intensive treatment ("Short Course") for previously untreated pulmonary MDR-TB patients but does not require universal drug susceptibility testing (DST) before Short Course. DST would likely screen out many MDR-TB patients in places like Mumbai with significant drug resistance. METHODS: MDR-TB patients at a private clinic were recruited for a prospective observational cohort. Short Course eligibility was evaluated by clinical criteria and DST results. Eligibility by DST was classified as rifampin monoresistance (as tested by Xpert MTB/RIF), rifampin, fluoroquinolones, and 2nd-line injectable drugs resistance (as tested by line probe assays) and resistance to other drugs. RESULTS: Of 559 participants with MDR-TB, 33% met clinical eligibility for Short Course. DST for rifampin, fluoroquinolones, and 2nd-line injectable drugs excluded 74.7% of participants. Complete phenotypic DST excluded 96.6% of participants. Prior treatment with either 1st or 2nd-line drugs did not significantly affect eligibility. CONCLUSIONS: In a global MDR-TB hotspot, < 5% of participants with MDR-TB were appropriate for Short Course by clinical characteristics and DST results. Rapid molecular testing would not sufficiently identify drug resistance in this population. Eligibility rates were not significantly reduced by prior TB treatment.