Family-centered Care for Sick Newborns: A Thumbnail View

Family-centered care (FCC) for sick newborns is emerging as a paradigmatic shift in the practice of facility-based newborn care. It seeks to transforming a provider-centered model into a client-centered one and thus build a new therapeutic alliance. FCC is the cornerstone of continuum of care, imparting caregiving competencies to parents/caregivers both within institutions as well as after the discharge. This has potential gains for the newborn, family members, and facility-level staff. The initial model piloted in tertiary-care settings is now undergoing translation at five sites across the country; the outcomes are keenly awaited.     

Histological observations on the anterior olfactory nucleus in human

Aim: Localization of isolated clusters of anterior olfactory nucleus (AON) in a human olfactory bulb and tract. Materials and methods: This investigation was done on human olfactory bulbs and their tracts, collected from the freshly donated cadavers, before embalming, in the Department of Anatomy, IPGMER, Kolkata. H&E stained histological slides were prepared along the whole length of specimens and examined under a Leica DM 2000 microscope and with a Leica Quin image analyzer. Results: The anterior olfactory nucleus was detected in the form of a major cluster and in two smaller clusters of neurons. The major cluster was located at the caudal pole of the bulb and was composed of medium-sized triangular cells which had an average diameter of 13.92 ± 3.43 μm. Out of the two minor clusters, one was detected at the beginning and another at the middle of the olfactory tract. Here neurons were little larger in size and their diameter ranged approximately 15–17 μm. Olfactory striae also accommodated some neurons in a scattered manner. Conclusion: This observation will be helpful in exploration of the complex role of AON in the organization and function of the olfactory system and its clinical significance in human.     

Thioredoxin-related protein of 14 kDa is an efficient L-cystine reductase and S-denitrosylase

Thioredoxin-related protein of 14 kDa (TRP14, also called TXNDC17 for thioredoxin domain containing 17, or TXNL5 for thioredoxin-like 5) is an evolutionarily well-conserved member of the thioredoxin (Trx)-fold protein family that lacks activity with classical Trx1 substrates. However, we discovered here that human TRP14 has a high enzymatic activity in reduction of l-cystine, where the catalytic efficiency (2,217 min⁻¹⋅µM⁻¹) coupled to Trx reductase 1 (TrxR1) using NADPH was fivefold higher compared with Trx1 (418 min⁻¹⋅µM⁻¹). Moreover, the l-cystine reduction with TRP14 was in contrast to that of Trx1 fully maintained in the presence of a protein disulfide substrate of Trx1 such as insulin, suggesting that TRP14 is a more dedicated l-cystine reductase compared with Trx1. We also found that TRP14 is an efficient S-denitrosylase with similar efficiency as Trx1 in catalyzing TrxR1-dependent denitrosylation of S-nitrosylated glutathione or of HEK293 cell-derived S-nitrosoproteins. Consequently, nitrosylated and thereby inactivated caspase 3 or cathepsin B could be reactivated through either Trx1- or TRP14-catalyzed denitrosylation reactions. TRP14 was also, in contrast to Trx1, completely resistant to inactivation by high concentrations of hydrogen peroxide. The oxidoreductase activities of TRP14 thereby complement those of Trx1 and must therefore be considered for the full understanding of enzymatic control of cellular thiols and nitrosothiols.The redox or nitrosylation state of reactive cysteine (Cys) residues in proteins can affect a multitude of intracellular events, either beneficial or harmful, depending upon biological context (1, 2). Two major cellular systems that control the redox states of Cys residues are the thioredoxin (Trx) and the glutathione (GSH) systems. The Trx system includes isoforms of Trx, Trx reductase (TrxR), and NADPH together with several Trx-dependent enzymes and proteins (3). The GSH/GSH disulfide redox couple is kept reduced by the NADPH-dependent activity of GSH reductase (GR) and donates electrons to isoforms of glutaredoxin (Grx) and other GSH-dependent enzymes (4).In addition to Trx, many proteins have a Trx fold and a Trx-like active-site sequence. One such protein is thioredoxin-related protein of 14 kDa (TRP14, also known as TXNDC17 or TXNL5), which is an evolutionarily well-conserved cytosolic and widely expressed Trx-fold protein that can be reduced by TrxR1 (5). Its crystal structure, compared with Trx1, shows additional structural features in the active site, thereby explaining its lack of activity with most classical Trx1 protein disulfide substrates including ribonucleotide reductase, insulin, peroxiredoxins, or methionine sulfoxide reductase (5–7). TRP14 was suggested to have evolved to exert specific signaling roles in cells and was identified as a modulator of TNFα/NFκB signaling pathways through interactions with the dynein light chain LC8 protein (6, 8). We previously found that treatment of cells with cisplatin triggered the formation of covalent cross-links between TrxR1 and either Trx1 or TRP14, which suggests that TRP14 is tightly linked to TrxR1 within the cellular context (9). Recently, we also found that TRP14 is able to reactivate oxidized phosphotyrosine phosphatase 1B, thereby indeed implicating specific functions in modulation of cellular signaling pathways (10).In addition to having general protein disulfide reductase activities, Trx1 is also a denitrosylase for a broad spectrum of nitrosoproteins and nitrosothiols (11, 12). Substrates include S-nitrosocaspase 3 (13, 14), S-nitrosocaspase 8 (15), S-nitrosoglutathione (GSNO) (16, 17), and S-nitrosocysteine (l-CysSNO) (12). Nitrosylation and denitrosylation reactions provide a regulatory mechanism for protein function and are thereby also involved in a variety of cellular signal transduction pathways. For example, S-nitrosylation of caspases can inhibit their activity and thus regulate apoptosis in resting cells (18, 19). A full understanding of NO homeostasis and its pathways is of medical importance because an aberrant formation of nitrosylated proteins has been implicated in a variety of diseases. However, protein denitrosylation is a hitherto less studied part in NO-mediated signaling (20, 21). In addition to Trx1, another enzyme mediating cellular denitrosylation reactions is GSNO reductase (GSNOR). GSNOR is the same enzyme as class III alcohol dehydrogenase, mainly catalyzing denitrosylation of GSNO using NADH as an electron donor (22, 23). In addition, S-denitrosylation activities are supported by protein disulfide isomerase (PDI) (24), carbonyl reductase 1 (25), and lipoic acid (17).The high intracellular concentrations of GSH are also important in NO metabolism because of facilitated formation of GSNO by reaction of GSH with NO or by denitrosylation of cellular nitrosothiols (20, 26). Because the synthesis of GSH depends upon availability, cellular uptake and reduction of sulfur-containing precursors such as l-cystine, l-cystine homeostasis is also important for GSH functions (27). l-Cystine is taken up into cells using different transport systems, e.g., the oxidative stress-inducible cystine/glutamate antiporter (system ) (28). The mechanism behind the reduction of l-cystine still has not been fully elucidated, but has been implicated to include GSH itself or also TrxR1-dependent systems (29).In the present study, we wanted to further characterize the enzymatic properties of TRP14, which revealed that the protein is at least as efficient as Trx1 in supporting reduction of specific redox substrates, such as l-cystine. In that assay, TRP14 is a fivefold better substrate for TrxR1 than Trx1 itself and, furthermore, more dedicated as its activity is not diminished in the presence of other Trx1 substrates that are not reduced by TRP14. Furthermore, we discovered that TRP14 is yet another cytosolic oxidoreductase that can catalyze S-denitrosylation reactions.     

Contribution of β-phenethylamine, a component of chocolate and wine, to dopaminergic neurodegeneration： implications for the pathogenesis of Parkinson＇s disease

While the cause of dopaminergic neuronal cell death in Parkinson＇s disease（PD）is not yet understood,many endogenous molecules have been implicated in its pathogenesis.β-phenethylamine（β-PEA）,a component of various food items including chocolate and wine,is an endogenous molecule produced from phenylalanine in the brain.It has been reported recently that long-term administration ofβ-PEA in rodents causes neurochemical and behavioral alterations similar to that produced by parkinsonian neurotoxins.The toxicity ofβ-PEA has been linked to the production of hydroxyl radical（.OH）and the generation of oxidative stress in dopaminergic areas of the brain,and this may be mediated by inhibition of mitochondrial complex-I.Another significant observation is that administration ofβ-PEA to rodents reduces striatal dopamine content and induces movement disorders similar to those of parkinsonian rodents.However,no reports are available on the extent of dopaminergic neuronal cell death after administration ofβ-PEA.Based on the literature,we set out to establishβ-PEA as an endogenous molecule that potentially contributes to the progressive development of PD.The sequence of molecular events that could be responsible for dopaminergic neuronal cell death in PD by consumption ofβ-PEA-containing foods is proposed here.Thus,long-term over-consumption of food items containingβ-PEA could be a neurological risk factor having significant pathological consequences.     

Development of a tetra-primer ARMS PCR-based assay for detection of a novel single-nucleotide polymorphism in the 5′ untranslated region of the bovine ITGB6 receptor gene associated with foot-and-mouth disease susceptibility in cattle

ITGB6 is known to be one of the major receptor components involved in host tropism of foot-and-mouth disease (FMD) virus in cattle. A competitive PCR technique called ARMS PCR was adapted to identify a single-nucleotide polymorphism (SNP), G29A, db SNP Id: rs109075046, in the 5′ untranslated region (5′UTR) of the bovine ITGB6 gene. Genotype profiling identified three kinds of genetic variation within the targeted SNP among Frieswal crossbred cattle. The occurrence of FMD in the three genotypes was further evaluated, revealing a clear role in the incidence of FMD in the studied population.     

Can nutrition rehabilitation centers address severe malnutrition in India?

Madhya Pradesh has made remarkable progress in facility based management of severe acute malnutrition, and has developed a model that is being replicated in many states. India has uniquely high prevalence of both stunting and wasting, implying that both severe acute malnutrition and severe chronic malnutrition co-exist. This study sought to explore design issues of nutritional rehabilitation centers in order to inform its effectiveness in settings where the prevalence of chronic poverty and malnutrition is high. Our analysis attributes the limited success (marked by poor cure rates and high non-responder rates) to high prevalence of chronic malnutrition, particularly in nutritional rehabilitation centers located in pheripheral areas. There is a failure to recognize severe chronic malnutrition as an epidemiological entity and gear wide-ranging programmatic and social interventions.     

Polio eradication initiative in India: deconstructing the GPEI.

The Global Polio Eradication Initiative (GPEI) promised eradication of polio by the year 2000 and certification of eradication by 2005. The first deadline is already a matter of history. With the reporting of polio cases in 2004, the new deadline for polio eradication by 2004 is postponed further. This article seeks to argue that the scientific and technical bodies spear-heading the GPEI, including the WHO, UNICEF, and the U.S. Centers for Disease Control, have formulated a conceptually flawed strategy and that it is not weak political will that is the central obstacle in this final push for global eradication. The validity of the claims of "near success" by the proponents of the GPEI is also examined in detail. By taking India as a case study, the authors examine the achievements of the GPEI in nine years of intense effort since 1995. They conclude that the GPEI is yet another exercise in mismanaging the health priorities and programs in developing countries in the era of globalization.     

Visceral leishmaniasis: consequences to women in a Bangladeshi community

Visceral leishmaniasis (VL) or kala-azar (KA) affects the rural poor, causing significant morbidity and mortality. We examined the epidemiological and social impact of KA in an affected village in Bangladesh. A population-based survey of the village residents showed a case fatality rate of 14.7% among females and 5.3% among males. Before initiation of the study, female patients were ill longer than males before they received treatment. Future work needs to focus on understanding the implications of KA on women and to develop sustainable strategies for appropriate and timely access to treatment.     

Successful switch (tOPV to bOPV) in India: Tribute to a resilient health system

In accordance with the end game strategies for polio eradication a synchronized switch plan from tOPV to bOPV was implemented globally in 2016. The National Committee for Polio Eradication (NCCPE) validated the switch activities in India. An expert group of 104 academics conducted field visits in 25 states and 2 Union territories for independent verification (after an initial round of verification by the National Polio Surveillance Project [NPSP]). The objectives were to validate withdrawal and disposal of tOPV by screening cold chain points in public and private sector health facilities in both rural and urban areas; additionally, availability of bOPV and IPV was also documented. 34 filled tOPV and 5 empty vials were detected inside cold chain equipment and 17 outside. The disposal mechanism was found to be reasonably adequate. The key strategies -- ‘throttling’ of vaccine supplies well ahead of the switch date while preventing stock outs at various immunization points, simultaneously working with the regulators to delicense the tOPV on the switch date and helping manufacturers to calibrate vaccine production according to national timelines, and strong and persistent advocacy with professional associations to align with national bOPV and IPV policy facilitated successful accomplishment of the switch process. Effective implementation of the switch strategy in India also bears testimony to the resilience of the health system operating under diverse and heterogeneous governance.