Application of Mono and Trinuclear Cyclometalated Iridium (III) Complexes in Differential Bacterial Imaging and Antimicrobial Photodynamic Therapy.

The application of transition metal complexes for antimicrobial photodynamic therapy (PDT) has emerged as an attractive alternative in mitigating a broad range of bacterial pathogens, including multidrug-resistant pathogens. In view of their photostability, long excited-state lifetimes, and tunable emission properties, transition metal complexes also contribute as bioimaging agents. In the present work, we designed mono and trinuclear cyclometalated iridium (III) complexes to explore their imaging application and antibacterial potential. For this, we used Methicillin-resistant S. aureus (MRSA), the most prevalent of community-associated (CA) multidrug-resistant (MDR) bacteria (CA MDR) and Lactococcus lactis (L. lactis) as Gram-positive while Campylobacter jejuni (C. jejuni) and E. coli as Gram-negative bacteria. In addition to differential bioimaging of these bacteria, we assessed the antibacterial effects of both mono and trinuclear Ir(III) complexes under exposure to 427 nm LED light. The data presented herein strongly suggest better efficacy of trinuclear Ir(III) complex over the mononuclear complex in imparting photoinduced cell death of MRSA. Based on the safety profile of these complexes, we propose that trinuclear cyclometalated iridium(III) complex holds great promise for selective recognition and targeting MDR bacteria with minimal off-target effect.

Phosphorescent Trinuclear Pt-Ir-Pt Complexes: Insights into the Photophysical and Electrochemical Properties and Interaction with Guanine Nucleobase.

In this study we have analysed the comparative photophysical and electrochemical properties of two isomeric heterotrinuclear PtII -IrIII -PtII complexes 3 and 6 and the four corresponding intermediate isomeric homonuclear cyclometalated iridium(III) complexes 1, 2, 4 and 5. The isomerisation originates from positional differences in the formyl, di-2-picolylamine and Pt-di-2-picolylamine moieties appended to cyclometalated or ancillary ligands. The interaction of 5'-GMP with the trinuclear complexes 3 and 6 shows that platinum centres appended to the cyclometalated ligand in 3 facilitate the binding of two 5'-GMP units per PtII centre in preference to a single 5'-GMP unit per PtII centre as observed in 6. The 1:2 and 1:1 PtII -5'-GMP binding patterns probably arise from the convenient arrangements of the Pt-di-2-picolylamine units in different planes in complex 3, which is absent in complex 6.

Selective depletion of Campylobacter jejuni via T6SS dependent functionality: an approach for improving chickens gut health.

The targeted depletion of potential gut pathogens is often challenging because of their intrinsic ability to thrive in harsh gut environments. Earlier, we showed that Campylobacter jejuni (C. jejuni) exclusively uses the Type-VI Secretion System (T6SS) to target its prey such as Escherichia coli (E. coli), and phenotypic differences between T6SS-negative and T6SS-positive C. jejuni isolates toward bile salt sensitivity. However, it remains unclear how the target-driven T6SS functionality prevails in a polymicrobial gut environment. Here, we investigated the fate of microbial competition in an altered gut environment via bacterial T6SS using a T6SS-negative and -positive C. jejuni or its isogenic mutant of the hemolysin-coregulated protein (hcp). We showed that in the presence of bile salt and prey bacteria (E. coli), T6SS-positive C. jejuni experiences enhanced intracellular stress leading to cell death. Intracellular tracking of fluorophore-conjugated bile salts confirmed that T6SS-mediated bile salt influx into C. jejuni can enhance intracellular oxidative stress, affecting C. jejuni viability. We further investigated whether the T6SS activity in the presence of prey (E. coli) perturbs the in vivo colonization of C. jejuni. Using chickens as primary hosts of C. jejuni and non-pathogenic E. coli as prey, we showed a marked reduction of C. jejuni load in chickens cecum when bile salt solution was administered orally. Analysis of local antibody responses and pro-inflammatory gene expression showed a reduced risk of tissue damage, indicating that T6SS activity in the complex gut environment can be exploited as a possible measure to clear the persistent colonization of C. jejuni in chickens.

Aqua-friendly organometallic Ir-Pt complexes: pH-responsive AIPE-guided imaging of bacterial cells.

In this work, the aggregation-induced photoluminescence emission (AIPE) of three water-soluble heterobimetallic Ir-Pt complexes was reported with insight into their photophysical and electrochemical properties and imaging of bacterial cells. An alkyne appended Schiff's base L, bridges bis-cyclometalated iridium(III) and platinum(II) terpyridine centre. The Schiff's base (N-N fragment) serves as the ancillary ligand to the iridium(III) centre, while the alkynyl end is coordinated to platinum(II). The pH and ionic strength influence the aggregation kinetics of the alkynylplatinum(II) fragment, leading to metal-metal and π-π interactions with the emergence of a triplet metal-metal-to-ligand charge transfer (3MMLCT) emission. The excellent reversibility and photostability of aggregation-induced emission (AIE) of these aqua-friendly complexes were tested for their ability to sense and selectively image E. coli cells at various pH values.

Relationship Between Vitamin D Level and Gestational Diabetes Mellitus: A Cross-Sectional Study.

Aim: To determine the correlation between vitamin D levels and gestational diabetes mellitus. Materials and Methods: Cross-sectional observational study, conducted in Gauhati Medical College and Hospital, over a period of 1 year, on 350 antenatal patients, with gestational age beyond 24 weeks, keeping in mind the inclusion and exclusion criteria. Age, obstetric score, religion, BMI were noted for all patients. They underwent screening for gestational diabetes mellitus using DIPSI (Diabetes in Pregnancy Study Group of India) guidelines and were divided into two groups. Vitamin D estimation by CLIA method (chemiluminescence method) was done in both groups and results were compared. Association between vitamin D levels and gestational diabetes mellitus was studied using Chi Square Test. Results: The prevalence of vitamin D deficiency in antenatal patients was found to be 63.7%. 73% of gestational diabetes mellitus patients were deficient in vitamin D. There was a statistically significant association seen between vitamin D level and Gestational diabetes mellitus (p value-0.046). There was 1.34 times increased risk of developing gestational diabetes mellitus when the vitamin D levels were deficient as compared to when the vitamin levels were within the normal range. Conclusion: There was a high level of vitamin D deficiency in the pregnant women of North East. Due to lack of screening of vitamin D levels, many pregnant women suffer from adverse feto-maternal outcomes. There is a need to identify them early in pregnancy, provide vitamin D supplementation and to decrease the likelihood of them developing complications.

Tuning the Organelle-Specific Imaging and Photodynamic Therapeutic Efficacy of Theranostic Mono- and Trinuclear Organometallic Iridium(III) Complexes.

The organelle-specific localization of mononuclear and trinuclear iridium(III) complexes and their photodynamic behavior within the cells are described herein, emphasizing their structure-activity relationship. Both the IrA2 and IrB2 complexes possess a pair of phenyl-benzothiazole derived from the -CHO moieties of mononuclear organometallic iridium(III) complexes IrA1 and IrB1, which chelates IrCp*Cl (Cp* = 1,2,3,4,5-pentamethylcyclopentadiene) to afford trinuclear complexes IrA3 and IrB3. Insights into the photophysical and electrochemical parameters of the complexes were obtained by a time-dependent density functional theory study. The synthesized complexes IrA2, IrA3, IrB2, and IrB3 were found to be nontoxic to human MCF7 breast carcinoma cells. However, the photoexcitation of complexes using LED light could effectively trigger intracellular reactive oxygen species (ROS) generation, leading to cell death. Furthermore, to check the organelle-specific localization of IrA2 and IrB2, we observed that both complexes could selectively localize in the endoplasmic reticulum. In contrast, trinuclear IrA3 and IrB3 accumulate in the nuclei. The photoexcitation of complexes using LED light could effectively trigger intracellular reactive oxygen species (ROS) generation, leading to cell death.

Eco-epidemiological risk factors for Japanese encephalitis in the endemic region of North East India: a hospital-based case-control study.

Purpose: Japanese encephalitis (JE) has emerged as a major public health concern in North East India due to its complex eco-epidemiological risk factors. The objective of this study was to understand the various risk factors associated with JE infection in the endemic study location. Methods: A hospital-based case-control study was conducted at Jorhat Medical College and Hospital from August 2017 to September 2018. The study participants included 49 confirmed JE cases with two control arms, one consisting of non-JE acute encephalitis syndrome (AES) patients (n = 91) and the other of non-JE non-AES patients (n = 140), admitted at the same time in the pediatric and medicine wards. A predesigned, pretested, structured questionnaire was used for data collection. Results: Univariate analysis revealed the following to be risk factors: age at onset, sex, religion, immunization status, proximity to pigs, proximity to paddy fields (<100 m), use of a mosquito net, impregnated mosquito net, mosquito repellent, and outdoor activities. Multiple logistic regression analysis identified age at onset (adjusted odds ratio [AOR], 20.900; 95% confidence interval [CI], 2.210-31.815) and proximity to pigs (AOR, 4.190; 95% CI, 1.592-11.040) as risk factors for the first control arm and proximity to paddy fields (<100 m) (AOR, 8.470; 95% CI, 2.0251-35.438) was the only risk factor found for second control arm, whereas impregnated mosquito nets (AOR, 0.082; 95% CI, 0.009-0.725) and mosquito repellent (AOR, 0.173; 95% CI, 0.052-0.575) were found to be associated with the second control arm. Conclusion: Age at onset, proximity to pigs, proximity to paddy fields (<100 m), impregnated mosquito nets, and mosquito repellent were the most significant risk factors for JE in the NE region to warrant public health actions.

Azadirachta indica A. Juss bark extract and its Nimbin isomers restrict ß-coronaviral infection and replication.

Emerging mutations in the SARS-CoV-2 genome pose a challenge for vaccine development and antiviral therapy. The antiviral efficacy of Azadirachta indica bark extract (NBE) was assessed against SARS-CoV-2 and m-CoV-RSA59 infection. Effects of in vivo intranasal or oral NBE administration on viral load, inflammatory response, and histopathological changes were assessed in m-CoV-RSA59-infection. NBE administered inhibits SARS-CoV-2 and m-CoV-RSA59 infection and replication in vitro, reducing Envelope and Nucleocapsid gene expression. NBE ameliorates neuroinflammation and hepatitis in vivo by restricting viral replication and spread. Isolated fractions of NBE enriched in Nimbin isomers shows potent inhibition of m-CoV-RSA59 infection in vitro. In silico studies revealed that NBE could target Spike and RdRp of m-CoV and SARS-CoV-2 with high affinity. NBE has a triterpenoids origin that may allow them to competitively target panoply of viral proteins to inhibit mouse and different strains of human coronavirus infections, suggesting its potential as an antiviral against pan-ß-Coronaviruses.

Profiles of institutional ethics committees and status of standard operating procedures in North East India.

Limited data are available regarding institutional ethics committees (IECs) and their standard operating procedures (SOPs) in North East (NE) India. An attempt was made to study the profiles of IECs and the status of their SOPs in health research institutes of NE India. Fourteen biomedical and health research institutes of NE India were reviewed. Only 12 of these 14 institutes had constituted their IECs. The IECs were multidisciplinary and multisectoral in nature; of the 12 institutes, 8 had adequate representation by age and seven committees had adequate representation by gender. In 11 out of 12 IECs, chairpersons were non-affiliated, and chairperson qualifications in 10 of 12 IECs were found to be in keeping with the National Ethical Guidelines for Biomedical and Health Research involving Human Participants, 2017, of the Indian Council of Medical Research (ICMR). There were no lay persons in 6 out of 12 IECs. Nine out of 12 institutes had framed their SOPs. Three out of nine IECs adopted all three types of reviews namely exemption from review, expedited review and full committee review. Six out of nine SOPs had adopted the provision of quarterly review meetings. Declarations of conflict of interest (CoI) were specified in seven out of nine SOPs. Five out of nine SOPs mentioned no voting power for members who declared CoI. Seven out of nine SOPs specified the designated office space, staff, and budget of the committee. Only 2 out of the 12 IECs were registered. Our findings concluded that the characteristics and composition of IECs of health research institutes in NE India are suboptimal. Most of the SOPs were not framed as per recommendations of the ICMR National Ethical Guidelines for Biomedical and Health Research Involving Human Participants, 2017, and were unregistered.

Trinuclear Organometallic Pt-Ir-Pt Complexes: Insights into Photophysical Properties, Amino Acid Binding and Protein Sensing.

The rational synthesis of trinuclear emissive organometallic complexes with two equivalent platinum(II) centres appended to the ancillary substituted 2,2'-bipyridyl ligand of the cyclometalated iridium(III) centre is reported here. The alkynyl-platinum moiety and cyclometalated iridium(III) centres have been separated through a non-conjugated CH2 -O-CH2 linkage. The emission titration with amino acids reveals that the complexes sense free amino acids. The luminescence sensing of BSA is thus attributed to the amino acid sensing ability of the complexes and confirmed by emission anisotropy and Far-UV CD spectral study. The decrease in α-helix in the CD spectra signifies the changes in the secondary structure of protein in presence of the complexes.

Luminescent terpyridine appended geminal bisazide and bistriazoles: multinuclear Pt(II) complexes and AIPE-based DNA detection with the naked eye.

We report square planar Pt(ii) complexes as luminescent biosensors for DNA detection in solution. The sensing is attributed to the aggregation induced bright red photoluminescence (AIPE) of the complexes in the presence of DNA that can be seen with the naked eye using only a 360 nm light source. Terpyridine appended luminescent geminal bistriazoles (L1-L4, from geminal bisazide A through azide-alkyne 'click' cycloaddition) with versatile chelating sites were explored for metal coordination and reaction with Pt(dmso)2Cl2 yielding tetranuclear and dinuclear complexes of Pt(ii) with different N∩N ligand environments. Thermally stable gem-bisazide and bistriazoles are hardly reported in the literature and this is the first report of terpyridine appended geminal bisazide and bistriazoles.

Clinico-epidemiological characteristics of hospitalized acute encephalitis syndrome children and their correlation with case fatality rate.

BACKGROUND: Acute Encephalitis Syndrome (AES) in children contributes considerable morbidity and mortality in endemic region. A study was conducted to see the clinico-epidemiological characteristics of hospitalized AES children and to find out if there is any correlation of clinico-epidemiological factors with case fatality rate (CFR). METHODS: This hospital-based observational prospective study was conducted in a tertiary care teaching hospital of Assam, India from 16th May, 2019 to 15th May, 2020. We enrolled clinically diagnosed 140 hospitalized AES children consecutively as per WHO case definition. Cerebrospinal fluid and serum samples were tested for JEV-specific IgM antibodies. RESULTS: Out of 140 AES children 84 (60%) were male and 5-12 years age group had the highest 79 (56.4%) number of cases. Primarily cases were from rural areas 132 (94.3%). In addition to fever, major clinical manifestations were seizures 114 (81.4%), altered sensorium 128 (91.4%), meningeal signs 62 (44.3%), and <8 GCS 42 (30%). CFR was 27.7%. Significantly high CFR was seen among AES children with GCS <8 (P-value 0.0001) and presence of meningeal signs (P-value 0.0007). A higher proportion of non-survivors 55.6% were non JE AES. Monthly incidence of AES/Death showed a peak in the month of July. CONCLUSION: AES in children is a significant public health problem in the study area with high CFR. Presence of GCS <8 and meningeal irritation are the important predictors of mortality in AES children. Preponderance of non-JE AES case fatality in children warrant further exploration and appropriate public health interventions.

A cyclometalated trinuclear Ir(iii)/Pt(ii) complex as a luminescent probe for histidine-rich proteins.

Organometallic complexes have important application in the field of protein staining, with potential for use in proteomic analysis. The rational synthesis of a trinuclear luminescent organometallic complex with two platinum(ii) centres appended to the cyclometalated ligand of the iridium(iii) centre is reported here. Two di-2-picolylamine groups bonded to the cyclometalated phenyl pyridine moiety provide three coordinating sites to each platinum centre. The replacement of chloride in the fourth coordination site of two square planar platinum metal centres with the imidazole nitrogen or sulphur atom of histidine/cysteine is evident from the change in luminescence intensity upon binding these amino acids. The increase in luminescence emission intensity upon binding of histidine to the organometallic complex allowed it to be used as a protein staining agent. Reversibility of staining upon washing with imidazole enhances the possibility of its application in mass spectrometric analysis.

An aggressive angiomyxoma of vulva - A rare entity - A case report.

Aggressive angiomyxoma is a rare, locally invasive mesenchymal tumor predominantly presenting in women of reproductive age and also having a moderate-to-high risk for local relapse. Hence, it needs to be differentiated from other mesenchymal tumors occurring in this region. We present here a case of a 40-year-old female presenting with a large, fleshy, pedunculated mass on the right labia majora.

Clinical profile and outcome of Japanese encephalitis in children admitted with acute encephalitis syndrome.

Japanese encephalitis (JE) is an arthropod borne viral disease. Children are most commonly affected in Southeast Asian region showing symptoms of central nervous system with several complications and death. The clinical characteristics and outcomes in pediatric JE patients hospitalized with acute encephalitis syndrome (AES) are still poorly understood. A prospective study was conducted in pediatric ward of Assam Medical College Hospital to evaluate the clinical profile and outcome of JE in children. A total of 223 hospitalized AES cases were enrolled during March to December 2012. Serum and cerebro spinal fluids were tested for presence of JE specific IgM antibody. 67 (30%) were found to be JE positive. The most common presenting symptoms in JE patients were fever (100%), altered sensorium (83.58%), seizure (82.08%), headache (41.79%), and vomiting (29.85%). Signs of meningeal irritation were present in 55.22% of cases. Around 40.29%, JE patients had GCS ≤ 8. Among the JE patients, 14.7% died before discharge. The complete recoveries were observed in 63.9% of cases, while 21.3% had some sort of disability at the time of discharge. JE is still a major cause of AES in children in this part of India. These significant findings thus seek attentions of the global community to combat JE in children.