Visible-Light-Responsive Novel Ru(II)-Metallo-Antibiotics with Potential Antibiofilm and Antibacterial Activity.

Growing challenges with antibiotic resistance pose immense challenges in combating microbial infections and biofilm prevention on medical devices. Lately, antibacterial photodynamic therapy (aPDT) is now emerging as an alternative therapy to overcome this problem. Herein, we synthesized and characterized four Ru(II)-complexes, viz., [Ru(ph-tpy)(bpy)Cl]PF6 (Ru1), [Ru(ph-tpy)(dpq)Cl]PF6 (Ru2), [Ru(ph-tpy)(dppz)Cl]PF6 (Ru3), and [Ru(ph-tpy)(dppn)Cl]PF6 (Ru4) (where 4'-phenyl-2,2':6',2″-terpyridine = ph-tpy; 2,2'-bipyridine = bpy; dipyrido[3,2-f:2',3'-h]quinoxaline = dpq; dipyrido[3,2-a:2',3'-c]phenazine = dppz; and Benzo[I]dipyrido[3,2-a:2',3'-c]phenazine = dppn), among which Ru2-Ru4 are novel. Octahedral geometry of the complexes with a RuN5Cl core was evident from the crystal structure of Ru2. Ru1-Ru4 showed an MLCT absorption band in the 450-600 nm region, useful for aPDT performances. Further, optimum triplet excited state energy and excellent photostability of Ru1-Ru4 made them good photosensitizers for aPDT. Ru1-Ru4 demonstrated enhanced antimicrobial activity on visible-light exposure (400-700 nm, 10 J cm-2), confirmed using different antibacterial assays. Mechanistic studies revealed that inhibition of bacterial growth was due to the generation of oxidative stress (via NADH oxidation and ROS generation) upon treatment with Ru2-Ru4, resulting in destruction of the bacterial wall. Ru2 performed best killing performance against both Gram-negative (Escherichia coli) and Gram-positive (Bacillus subtilis) bacteria when exposed to light. Ru2-Ru4, when coated on a polydimethylsiloxane (PDMS) disk, showed long-term reusability and durable antibiofilm properties. Molecular docking confirmed the efficient interaction of Ru2-Ru4 with FabH (regulates fatty acid biosynthesis of E. coli) and PgaB (gives structural stability and helps biofilm formation of E. coli), resulting in probable downregulation. In vivo studies with healthy Wistar rats confirmed the biocompatibility of Ru2. This study shows that these lead complexes (Ru2-Ru4) can be used as potent alternative antimicrobial agents in low concentrations toward bacterial eradication with photodynamic therapy (PDT).

Quality improvement and outcomes for neonates with hypoxic-ischemic encephalopathy: obstetrics and neonatal perspectives.

Despite significant improvement in perinatal care and research, hypoxic ischemic encephalopathy (HIE) remains a global healthcare challenge. From both published research and reports of QI initiatives, we have identified a number of distinct opportunities that can serve as targets of quality improvement (QI) initiatives focused on reducing HIE. Specifically, (i) implementation of perinatal interventions to anticipate and timely manage high-risk deliveries; (ii) enhancement of team training and communication; (iii) optimization of early HIE diagnosis and management in referring centers and during transport; (iv) standardization of the approach when managing neonates with HIE during therapeutic hypothermia; (v) and establishment of protocols for family integration and follow-up, have been identified as important in successful QI initiatives. We also provide a framework and examples of tools that can be used to support QI work and discuss some of the perceived challenges and future opportunities for QI targeting HIE.

Synthesis of a Highly Selective Scavenger of Precious Metals from a Printed Circuit Board Based on Cellulose Filter Paper Functionalized with a Grafted Polymer Chain Bearing N-Methyl-2-hydroxyethylcarbamothioate Moieties.

We report the synthesis and practical application of a novel scavenger for precious metals. The scavenger was prepared from cellulose filter paper with grafted chains of poly(glycidyl methacrylate) modified with a novel ligand group of N-methyl-2-hydroxyethylcarbamothioate moieties, introduced by the reaction with O-1-mercapto-3-phenoxypropan-2-yl N-methyl-2-hydroxyethylcarbamothioate. Batch experiments were performed to evaluate the capability of the scavenger in ranges of pH and acid concentration as well as to determine the kinetics and isotherm models. The scavenger was found to adsorb only Ag(I), Pd(II), and Au(III) from an aqueous media in the presence of coexisting ions of different bases and precious metals at wide ranges of pH and acid concentration. The adsorption rates fit a pseudo-second-order kinetic equation, and the adsorption reached equilibrium within 60 min. The isotherm studies indicated that the obtained data were a good fit with the Langmuir model. The maximum adsorption capacities of Ag(I), Pd(II), and Au(III) were 126.95, 124.67, and 230.67 mg g-1, respectively. Regeneration experiments indicated that the adsorbent maintained 97% of its initial efficiency even after five adsorption/desorption cycles. The scavenger was effectively utilized to recover Ag(I), Pd(II), and Au(III) from an aqua regia solution of waste printed circuit boards.

SARS-CoV-2 infection reduces human nasopharyngeal commensal microbiome with inclusion of pathobionts.

The microbiota of the nasopharyngeal tract (NT) play a role in host immunity against respiratory infectious diseases. However, scant information is available on interactions of SARS-CoV-2 with the nasopharyngeal microbiome. This study characterizes the effects of SARS-CoV-2 infection on human nasopharyngeal microbiomes and their relevant metabolic functions. Twenty-two (n = 22) nasopharyngeal swab samples (including COVID-19 patients = 8, recovered humans = 7, and healthy people = 7) were collected, and underwent to RNAseq-based metagenomic investigation. Our RNAseq data mapped to 2281 bacterial species (including 1477, 919 and 676 in healthy, COVID-19 and recovered metagenomes, respectively) indicating a distinct microbiome dysbiosis. The COVID-19 and recovered samples included 67% and 77% opportunistic bacterial species, respectively compared to healthy controls. Notably, 79% commensal bacterial species found in healthy controls were not detected in COVID-19 and recovered people. Similar dysbiosis was also found in viral and archaeal fraction of the nasopharyngeal microbiomes. We also detected several altered metabolic pathways and functional genes in the progression and pathophysiology of COVID-19. The nasopharyngeal microbiome dysbiosis and their genomic features determined by our RNAseq analyses shed light on early interactions of SARS-CoV-2 with the nasopharyngeal resident microbiota that might be helpful for developing microbiome-based diagnostics and therapeutics for this novel pandemic disease.

Clinical and laboratory profile of patients with Kyasanur forest disease: A single-centre study of 192 patients from Karnataka, India.

INTRODUCTION: Kyasanur forest disease (KFD) is a biphasic tick-borne viral fever that is endemic to 16 districts and five states of Southern India. The aim of this study was to describe the clinical/ laboratory manifestations of KFD. MATERIALS AND METHODS: This is a retrospective cohort study of confirmed KFD patients admitted in our hospital between December 2018 and June 2019. The demographic, clinical and laboratory parameters of patients during the first and second phase of illness was recorded in a pre-defined case study form. RESULTS: A total of 192 patients from Karnataka were diagnosed with a mean age of 46.2 ± 15.6 years and a male preponderance (57 %). Fever (99 %), myalgia (52 %), headache (43 %), cough (14 %), conjunctival congestion (14 %), altered sensorium (13 %) and haemorrhagic manifestations (8%) were seen in the first phase. A total of 18 % of the patients came back with a second febrile episode. The features of meningoencephalitis were seen in 34 % of the patients during the second phase. Leucopenia, thrombocytopenia, and increase in liver enzymes, creatine phosphokinase (CPK) and activated partial thromboplastin time (APTT) was seen in the first phase but not in the second phase. Higher age, myocarditis, altered sensorium in the first phase, hypotension at admission, lower platelet count, elevated liver enzymes, higher APTT and CPK, were significantly associated with mortality. CONCLUSION: The primary care physicians or travel medicine practitioners should be aware of the distinct clinical and laboratory manifestations of KFD, including the ones that may signify requirements of higher levels of care.

Coding-Complete Genome Sequences of Three SARS-CoV-2 Strains from Bangladesh.

We report the sequencing of three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Bangladesh. We have identified a unique mutation (NSP2_V480I) in one of the sequenced genomes (isolate hCoV-19/Bangladesh/BCSIR-NILMRC-006/2020) compared to the sequences available in the Global Initiative on Sharing All Influenza Data (GISAID) database. The data from this analysis will contribute to advancing our understanding of the epidemiology of SARS-CoV-2 in Bangladesh as well as worldwide at the molecular level and will identify potential new targets for interventions.

Twenty-five years of advocacy for patients with gastroparesis: support group therapy and patient reported outcome tool development.

BACKGROUND: Gastroparesis (Gp) is a poorly understood chronic gastrointestinal medical condition for which patient reported outcomes (PRO) are lacking. Previously developed symptoms scoring has been used for several decades. Using symptoms scores as a basis for documentation, 12 years of support/focus group patient feedback from the nearly 1000 attendees were integrated with medical care and recommendations for treatment were developed. Early attenders of the support group were compared with non-attendees for illness acuity, disability, and duration and number of office phone calls. METHODS: Patients cared for in an academic medical practice were assessed for patient-derived PRO symptoms, coupled with standardized Health Related Quality of Life (HRQOL) measures. Based on factors identified by the patients via support/focus groups, a diagnostic and prognostic tool was developed. RESULTS: The new tool utilized PRO symptoms and included provider assessments of medical illnesses as well as resource utilization. This 'post PRO' tool has been applied in a variety of settings for patients with the symptoms of Gp over the last two decades. The 'pre-PRO' factors from the support/focus groups were compared to the PRO measures as well as the 'post-PRO' scale to assess their usefulness. Using methods that combine chart data, including electronic medical records (EMR), with PRO symptoms may have design implications for PRO assessment. The resultant scales, as part of a new tool, can allow for sharing of PRO derived scores in a chronic gastrointestinal (GI), illness with different practitioners. CONCLUSIONS: These newly-derived scales offer a potentially useful tool for clinical decision-making, tailoring treatment to patient subgroups and engaging both patients and their families and caregivers in more active partnerships with providers to improve health outcomes.

The Application of Modern Dressings to Buruli Ulcers: Results from a Pilot Implementation Project in Ghana.

Buruli ulcer (BU) is a tropical, infectious skin disease. The resulting ulcer can take a long time to heal, and a high standard of wound care is essential. Currently, the only dressing used for BU wound care is gauze, and its removal causes pain and bleeding. We performed a pilot implementation project using HydroTac(®) (HARTMANN, Heidenheim, Germany), a modern dressing combining foam with a hydrogel component. For future BU treatment, we recommend to use a more absorbent dressing than the HydroTac dressing used in the current project. However, we show that modern dressings can be applied to BUs and that HydroTac dressings yield clean, healing wounds, and prevent the pain and bleeding associated with gauze dressings. Wound care is a vital but to date neglected aspect of BU management.