Cyclometalated Iridium(III) Complex with Substituted Benzimidazole: pH Directed Organelle-specific Localization within Lysosome.

We report the synthesis and pH dependent emission spectral behaviour of four emissive iridium(III) complexes (Ir1 - Ir4) with two isomeric pairs of bis-trifluoromethyl appended benzimidazole ligands. The imidazolyl hydrogen(N-H) has been replaced by phenyl groups (N-Ph) in two ligands to understand the impact of hydrogen bonding on the photophysical properties of the complexes and it indeed plays interesting role in the charge-transfer dynamics. The pH dependent electronic spectral change is observed for two of the complexes. The enhancement of emission intensity is observed at different wavelength for pH < 7 and pH > 7 for Ir1 and Ir3. The emission sensing of biogenic amines with pka values ranging from 5.80 - 9.74 is reported along with cellular imaging. The complex Ir1 specifically localizes within lysosome (pH = 4.5 - 5) and thus image this organelle with great precision. The detail electronic spectra and electrochemical behaviour were reported here along with TDDFT results.

Ifit2 restricts murine coronavirus spread to the spinal cord white matter and its associated myelin pathology.

Interferon-induced protein with tetratricopeptide repeats 2, Ifit2, is critical in restricting neurotropic murine-ß-coronavirus, RSA59 infection. RSA59 intracranial injection of Ifit2-deficient (-/-) compared to wild-type (WT) mice results in impaired acute microglial activation, reduced CX3CR1 expression, limited migration of peripheral lymphocytes into the brain, and impaired virus control followed by severe morbidity and mortality. While the protective role of Ifit2 is established for acute viral encephalitis, less is known about its influence during the chronic demyelinating phase of RSA59 infection. To understand this, RSA59 infected Ifit2-/- and Ifit2+/+ (WT) were observed for neuropathological outcomes at day 5 (acute phase) and 30 post-infection (chronic phase). Our study demonstrates that Ifit2 deficiency causes extensive RSA59 spread throughout the spinal cord gray and white matter, associated with impaired CD4+ T and CD8+ T cell infiltration. Further, the cervical lymph nodes of RSA59 infected Ifit2-/- mice showed reduced activation of CD4+ T cells and impaired IFNγ expression during acute encephalomyelitis. Interestingly, BBB integrity was better preserved in Ifit2-/- mice, as evidenced by tight junction protein Claudin-5 and adapter protein ZO-1 expression surrounding the meninges and blood vessels and decreased Texas red dye uptake, which may be responsible for reduced leukocyte infiltration. In contrast to sparse myelin loss in WT mice, the chronic disease phase in Ifit2-/- mice was associated with severe demyelination and persistent viral load, even at low inoculation doses. Overall, our study highlights that Ifit2 provides antiviral functions by promoting acute neuroinflammation and thereby aiding virus control and limiting severe chronic demyelination. IMPORTANCE Interferons execute their function by inducing specific genes collectively termed as interferon-stimulated genes (ISGs), among which interferon-induced protein with tetratricopeptide repeats 2, Ifit2, is known for restricting neurotropic viral replication and spread. However, little is known about its role in viral spread to the spinal cord and its associated myelin pathology. Toward this, our study using a neurotropic murine ß-coronavirus and Ifit2-deficient mice demonstrates that Ifit2 deficiency causes extensive viral spread throughout the gray and white matter of the spinal cord accompanied by impaired microglial activation and T cell infiltration. Furthermore, infected Ifit2-deficient mice showed impaired activation of T cells in the cervical lymph node and relatively intact blood-brain barrier integrity. Overall, Ifit2 plays a crucial role in mounting host immunity against neurotropic murine coronavirus in the acute phase while preventing mice from developing viral-induced severe chronic neuroinflammatory demyelination, the characteristic feature of human neurological disease multiple sclerosis (MS).

Interaction of arsenic with gap junction protein connexin 43 alters gap junctional intercellular communication.

Chronic exposure to Arsenic pollution in ground water is one of the largest environmental health disasters in the world. The toxicity of trivalent Arsenicals primarily happens due to its interaction with sulfhydryl groups in proteins. Arsenic binding to the protein can change the conformation of the protein and alter its interactions with other proteins leading to tissue damage. Therefore, much importance has been given to the studies of Arsenic bound proteins, for the purpose of understanding the origins of toxicity and to explore therapeutics. Here we study the dynamic effect of Arsenic on Connexin 43 (Cx43), a protein that forms the gap junctions, whose alteration deeply perturbs the cell-to-cell communication vital for maintaining tissue homeostasis. In silico molecular modelling and in vitro studies comparing Arsenic treated and untreated conditions show distinct results. Gap junction communication is severely disrupted by Arsenic due to reduced availability of unaltered Cx43 in the membrane bound form. In silico and Inductively Coupled Plasma Mass Spectrometry studies revealed the interaction of Arsenic to the Cx43 preferably occurs through surface exposed cysteines, thereby capping the thiol groups that form disulfide bonds in the tertiary structure. This leads to disruption of Cx43 oligomerization, and altered Cx43 is incompetent for transportation to the membrane surface, often forming aggregates primarily localizing in the endoplasmic reticulum. Loss of functional Cx43 on the cell surface have a deleterious effect on cellular homeostasis leading to selective vulnerability to cell death and tissue damage.

Comparison of volume and frequency advancement feeding protocols in very low birth weight neonates.

OBJECTIVE: To determine the outcomes in very low birth weight (VLBW) neonates receiving volume advancement versus frequency advancement feeding protocols. METHODS: This controlled clinical trial was conducted in Children Hospital Multan within duration of 6 months from February 2017 to August 2017. VLBW neonates having weight < 1500 g at the time of birth were included. The protocol for frequency advancement (FA) group was to give 1 ml/kg human or pre-formula milk after every 8 hours and in volume advancement (VA) group after every 3 hours initially. After three days, in FA group duration of feeds was decreased gradually from 8 to 2 hours and feed volume of 10 ml.kg-1.day-1 until full-recommended dose of feeding i.e. 150 ml.kg-1.day-1 reached. While in VA group, volume of 20 ml.kg-1.day-1 was given until full-recommended dose of feeding reached. Days to achieve full feed, weight gain, and length of hospital stay were primary study outcomes. RESULTS: Baseline weight of neonates was 1148 (111) grams in VA 1179 (106) grams in FA groups (p-value 0.18). In VA group, full feed was achieved in 11.04 (2.38) days versus 15.76 (2.48) days in FA group (P-value <0.001). Duration of IV fluid therapy were 13.5 (8.4) days in FA group versus 9.4 (7.6) in VA group (p-value <0.001). Moreover weight gain at the end of feeding protocol was significantly higher in VA group 1440 (78) grams versus 1284 (99) grams in FA group (P-value <0.001). Necrotizing entero-colitis occurred in only one neonate that was belonging to volume advancement group. CONCLUSION: Volume advancement (VA) feeding is better as compared to frequency advancement (FA) feeding in very low birth weight neonates.

Pattern of neonatal admission at the Children's Hospital and the Institute of Child Health, Multan.

BACKGROUND: Neonatology is a rapidly growing paediatric sub-specialty all over the world. Neonatal disease pattern changes from time to time and place. Analyzing the neonatal admission pattern helps the policy makers to make the better strategies and health care givers to serve better. METHOD: This was a descriptive study. The study data was collected of the patient admitted in neonatal unit of Children Hospital Complex and Institute of Child Health, Multan, Pakistan from 1st January 2010 to 31st December 2010. The data of all the admitted neonates was analysed according to their causes of admission in whole one year whether admitted through emergency department or OPD clinic. RESULT: Total numbers of neonatal admissions were 3,560. Birth asphyxia was found to be major cause of admission, 1,230 patients (34.5%). Among infections, sepsis was found in as a whole in 1,009 (28.3%) of admission, pneumonia in 170 (4.7%) and meningitis in 30 (0.8%). Out of 3,560 patients admitted, 2,550 were discharged after improvement, 290 died, and 720 left against medical advice (LAMA). CONCLUSION: Birth asphyxia, sepsis and prematurity are the main reasons for admission in neonatal age. By paying good attention to perinatal services, we can reduce morbidity and mortality in neonates.

Effect of Fortified Human Milk on the Growth Parameters of Babies With Very Low Birth Weight.

Objective The objective of this study is to assess the effect of fortified human milk on growth parameters of very low birth-weight babies. Study place and duration This randomized controlled trial took place at the neonatal intensive care unit (NICU), Children's Hospital, and Institute of Child Health in Multan from the 1st of January 2020 to the 1st of July 2021. Material and methods In group I, 25ml human milk was fortified with a 1g human milk fortifier (HMF) sachet (1g of HMF gives 4kcal added to 25ml of human milk). In group II, newborns were fed preterm formula (493 kcal/100 g where 0.8 g=4 kcal added to 25 ml of human milk) mixed with human milk. Infants were administered human milk + olive oil (0.4 mL = 4Kcal per 25ml human milk) in group III. Everyday weight gain, digestive intolerance (vomiting and/or abdominal distension), sepsis, hospital stay, electrolyte imbalance (derangement of serum sodium, potassium, chloride, and magnesium levels), albumin, and cholesterol/triglyceride levels were assessed. The data was analyzed through descriptive and inferential means using Pearson's chi-square tests and one-way analysis of variance (ANOVA). Results Results indicate that preterm formula infants gain higher weight compared to human fortifier infants and olive oil. Similarly, the difference was statistically significant (p=0.001). However, olive oil infants gained a lower head circumference compared to the other two groups, and the difference was statistically significant as well (p=0.000). Moreover, feeding intolerance and electrolyte imbalance were higher in olive oil infants, p=0.020 and p=0.024, respectively. Conclusion It can be concluded that the use of and preterm formula can prove beneficial in increasing the growth rate in terms of weight gain, length gain, and head circumference.