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Globally, millions of diabetic patients require daily life-saving insulin injections. Insulin heat-lability and fibrillation pose significant challenges, especially in parts of the world without ready access to uninterrupted refrigeration. Here, we have synthesized four human insulin analogs by conjugating ε-amine of B29 lysine of insulin with acetic acid, phenylacetic acid, alanine, and phenylalanine residues. Of these, phenylalanine-conjugated insulin, termed FHI, was the most stable under high temperature (65 °C), elevated salt stress (25 mM NaCl), and varying pH levels (ranging from highly acidic pH 1.6 to physiological pH 7.4). It resists fibrillation for a significantly longer duration with sustained biological activity in in vitro, ex vivo, and in vivo and displays prolonged stability over its native counterpart. We further unravel the critical interactions, such as additional aromatic π-π interactions and hydrogen bonding in FHI, that are notably absent in native insulin. These interactions confer enhanced structural stability of FHI and offer a promising solution to the challenges associated with insulin heat sensitivity.

Mammalian Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) and Drosophila Yorkie (Yki) are transcription cofactors of the highly conserved Hippo signaling pathway. It has been long assumed that the YAP/TAZ/Yki signaling drives cell proliferation during organ growth. However, its instructive role in regulating developmentally programmed organ growth, if any, remains elusive. Out-of-context gain of YAP/TAZ/Yki signaling often turns oncogenic. Paradoxically, mechanically strained, and differentiated squamous epithelia display developmentally programmed constitutive nuclear YAP/TAZ/Yki signaling. The unknown, therefore, is how a growth-promoting YAP/TAZ/Yki signaling restricts proliferation in differentiated squamous epithelia. Here, we show that reminiscent of a tumor suppressor, Yki negatively regulates the cell growth-promoting PI3K/Akt/TOR signaling in the squamous epithelia of Drosophila tubular organs. Thus, downregulation of Yki signaling in the squamous epithelium of the adult male accessory gland (MAG) up-regulates PI3K/Akt/TOR signaling, inducing cell hypertrophy, exit from their cell cycle arrest, and, finally, culminating in squamous cell carcinoma (SCC). Thus, blocking PI3K/Akt/TOR signaling arrests Yki loss-induced MAG-SCC. Further, MAG-SCCs, like other lethal carcinomas, secrete a cachectin, Impl2--the Drosophila homolog of mammalian IGFBP7--inducing cachexia and shortening the lifespan of adult males. Moreover, in the squamous epithelium of other tubular organs, like the dorsal trunk of larval tracheal airways or adult Malpighian tubules, downregulation of Yki signaling triggers PI3K/Akt/TOR-induced cell hypertrophy. Our results reveal that Yki signaling plays an instructive, antiproliferative role in the squamous epithelia of tubular organs. [ABSTRACT FROM AUTHOR]

Human ETS Related Gene, ERG, a master transcription factor, turns oncogenic upon its out-of-context activation in diverse developmental lineages. However, the mechanism underlying its lineage-specific activation of Notch (N), Wnt, or EZH2—three well-characterized oncogenic targets of ERG—remains elusive. We reasoned that deep homology in genetic tool kits might help uncover such elusive cancer mechanisms in Drosophila. By heterologous gain of human ERG in Drosophila, here we reveal Chip, which codes for a transcriptional coactivator, LIM-domain-binding (LDB) protein, as its novel target. ERG represses Drosophila Chip via its direct binding and, indirectly, via E(z)-mediated silencing of its promoter. Downregulation of Chip disrupts LIM–HD complex formed between Chip and Tailup (Tup)—a LIM–HD transcription factor—in the developing notum. A consequent activation of N-driven Wg signaling leads to notum-to-wing transdetermination. These fallouts of ERG gain are arrested upon a simultaneous gain of Chip, sequestration of Wg ligand, and, alternatively, loss of N signaling or E(z) activity. Finally, we show that the human LDB1, a homolog of Drosophila Chip, is repressed in ERG-positive prostate cancer cells. Besides identifying an elusive target of human ERG, our study unravels an underpinning of its lineage-specific carcinogenesis. [ABSTRACT FROM AUTHOR]

A recessive semi-lethal mutation resulting from the insertion of a P-lacW transposon at the cytological position 23A on the polytene chromosomes of Drosophila melanogaster was found to affect the unfolding and expansion of the wings resulting in a loss of venation and a marked decrease in their size. Lethality was polyphasic with numerous animals dying during early larval development and displaying apparently collapsed tracheal trees. The gene was therefore designated as congested-like tracheae, or colt. The colt mutation resulted from the insertion of a P-lacW transposon within the coding region of a 1.4-kb transcript. Wild-type function was restored by inducing a precise excision of the P-lacW transposon, while a deletion of the colt locus, produced by imprecise excision of the P element, showed a phenotype similar to that of the original P insert. The colt gene consists of a single exon and encodes a protein of 306 amino acids made of three tandem repeats, each characterized by two predicted transmembrane segments and a loop domain. The COLT protein shares extensive homology with proteins in the mitochondrial carrier family and particularly with the DIF-1 protein of Caenorhabditis elegans, which has been shown to be maternally required for embryonic tissue differentiation. Our analysis revealed that zygotic colt function is dispensable for normal embryonic morphogenesis but is required for gas-filling of the tracheal system at hatching time of the embryo and for normal epithelial morphogenesis of the wings.

Genetic mosaics of Drosophila mutant for lethal(2)giant larvae (lgl) were studied to demonstrate that cells lacking the lgl tumor suppressor gene do not promote cell-cell interactions during development. Cells from adult wings mutant for lgl showed abnormal growth and differentiation, indicating defective cell-cell interactions. Further evidence also showed that cells exhibiting neoplastic transformation of imaginal discs also show loss of normal signaling in addition to aberrant cell-cell interactions.

Hypothyroidism is a commonly encountered problem in daily clinical practice. Although the management of hypothyroidism may seem straightforward, it can become challenging when patients’ Thyroid-Stimulating Hormone (TSH) values remain elevated despite treatment. Various factors, including non-adherence and malabsorption, can contribute to this issue. Consequently, it is crucial to identify the underlying cause of increased levothyroxine demand, as this will prevent unnecessary dosage adjustments of levothyroxine tablets. In this case, a 13-year-old girl patient, presented with a TSH level greater than 200 and an fT4 level of 0.34, along with absent secondary sexual characteristics, impaired memory, delayed puberty, easy susceptibility to anxiety, difficulty with memorisation, and poor academic performance. Despite repeated inquiries, neither she nor her mother reported any instances of non-compliance. Additionally, there were no signs suggestive of malabsorption, such as diarrhoea or oedema. Therefore, a levothyroxine absorption test was conducted to rule out pseudo-malabsorption. This test aids in distinguishing patients with non-compliance from those with true malabsorption, thereby avoiding unnecessary dosage adjustments of levothyroxine supplementation, a problem frequently encountered in day-to-day clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Disturbances of intra-ventricular conduction are associated with distinct ECG abnormalities inpatients and QTc interval is found to be prolonged which may be interpreted as higher arrhythmogenic property of such patients. But the repolarisation time of such patients are more or less same which isexpressed by JTc interval. In this study, it is found that JTc interval measurement is more significant than QTc interval in IVCD patients as predictor of cardiac arrhythmogenesis. Methodology: Institution based observational, cross sectional study among 100 patients attending cardiology OPD for a period of approximate 2 years with diagnosis of different IVCDs (RBBB, LBBB, BFB) on surface ECG .QRS, QTc, JTc interval were measured. Result: Mean QRS and QTc value were more for LBBB group as compared to RBBB and BFB group. But corrected JTc value was more or less equal in three groups. Post HOC analysis showed that there was no significant correlation of JTc interval between all the three groups. JTc interval was not found to be statistically significant indicating that repolarisation abnormality is minimum in both RBBB, LBBB and BFB group. Conclusion: JTc interval is not significantly high in LBBB patients indicating long QTcin LBBB is due to depolarization abnormality rather than repolarisation abnormality and not a predictor of arrhythmogenesis. [ABSTRACT FROM AUTHOR]

Orientiatsutsugumashi (erstwhile Rickettsia tsutsugumashi) is an obligate intracellular bacteria that is showing re-emergence in the last decade in eastern India. 1-3 Commonly it causes acute febrile illness with rash and multiple organ involvement including CNS - In fact, Scrub encephalopathy has become a common cause of AES in recent times. Although pathogenesis of Scrub typhus is still uncertain, research on other Rickettsiales suggest infection of endothelial cells and vascular dysfunction to be the main mechanism. Based on that pathology we report two very rare manifestations - Acute Ischaemic Stroke and DVT in a single patient of Scrub typhus, occurring simultaneously. No such simultaneous occurrence has been reported in literature till date. [ABSTRACT FROM AUTHOR]

Planar Cell Polarity (PCP) is an evolutionarily conserved characteristic of animal tissues marked by coordinated polarization of cells or structures in the plane of a tissue. In insect wing epithelium, for instance, PCP is characterized by en masse orientation of hairs orthogonal to its apical-basal axis and pointing along the proximal-distal axis of the organ. Directional cue for PCP has been proposed to be generated by complex sets of interactions amongst three proteins - Fat (Ft), Dachsous (Ds) and Four-jointed (Fj). Ft and Ds are two atypical cadherins, which are phosphorylated by Fj, a Golgi kinase. Ft and Ds from adjacent cells bind heterophilically via their tandem cadherin repeats, and their binding affinities are regulated by Fj. Further, in the wing epithelium, sub-cellular levels of Ft-Ds heterodimers are seen to be elevated at the distal edges of individual cells, prefiguring their PCP. Mechanisms generating this sub-cellular asymmetry of Ft-Ds heterodimer in proximal and distal edges of cells, however, have not been resolved yet. Using a mathematical modeling approach, here we provide a framework for generation of this sub-cellular asymmetry of Ft-Ds heterodimer. First, we explain how the known interactions within Ft-Ds-Fj system translate into sub-cellular asymmetry of Ft-Ds heterodimer. Second, we show that this asymmetric localization of Ft-Ds heterodimer is lost when tissue-level gradient of Fj is flattened, or when phosphorylation of Ft by Fj is abolished, but not when tissue-level gradient of Ds is flattened or when phosphorylation of Ds is abrogated. Finally, we show that distal enrichment of Ds also amplifies Ft-Ds asymmetry. These observations reveal that gradient of Fj expression, phosphorylation of Ft by Fj and sub-cellular distal accumulation of Ds are three critical elements required for generating sub-cellular asymmetry of Ft-Ds heterodimer. Our model integrates the known experimental data and presents testable predictions for future studies. [ABSTRACT FROM AUTHOR]

Context: Hypothyroidism is a common public health problem in India. With iodine suficiency, autoimmune thyroiditis is becoming the most important etiology of hypothyroidism. Often, thyroiditis is associated with other systemic autoimmune diseases. Aims: We undertook thisobservational study to ind the prevalence of systemic lupus erythematosus (SLE) amongst the hypothyroid patients at our Institution. Settings and Design: This is probably the irst study of its kind from India. Materials and Methods: 185 patients with diagnosed hypothyroidism were included and screening for SLE was done by standard epidemiological criteria. Majority of the patients (63.8%) were young adults (20-40 years). Statistical Analysis Used: Two by two contingency tables were analyzed by Chi-square test or Fisher's exact test as needed. Logistic regression model was used considering the presence of SLE as a dependent variable. Results: Eleven (5.94%) patients were found to have SLE. However, anti nuclear factor was positive in 145 cases (78.4%). Of the patients with SLE, 8 (72.7%) were found to be anti TPO positive, but the titers of ANF and anti TPO did not correlate. Presence of discoid rash, haematological criteria and presence of antibodies like anti-dsDNA were signiicantly correlated with the presence of SLE in hypothyroid patients. Presence of ANF was also correlated with the grade of goiter (r=0.62; P<0.05). Also four patients with SLE had a positive family history (OR=9.37). Logistic regression model showed anti-TPO has OR=1.54 (P=0.02) for the development of SLE. Conclusions: Prevalence of SLE in hypothyroid patients is high compared to the general population, especially, as thyroiditis is very common in SLE. [ABSTRACT FROM AUTHOR]

Carotid intima media thickness (CIMT) is used commonly as a non-invasive test for assessment of degree of atherosclerosis. The present study, in a tertiary care centre of Eastern India was aimed to determine the relation between CIMT and the known and novel risk factors of ischemic stroke. Of the 62 patients studied, 82% were hypertensive and 61% were smokers, 95% were above 50 years of age. Seventy one percent of our patients had high CIMT. CIMT was significantly related to high sensitivity C-reactive protein (hsCRP), fibrinogen, LDL levels and age of the patient. By logistic regression analysis, hsCRP, fibrinogen and age were significantly associated with high CIMT. When the patients have elevation of both hsCRP and fibrinogen, the risk of high CIMT were even higher. Our study highlights the needs for better screening in high risk patients. [ABSTRACT FROM AUTHOR]

In a screen for Drosophila genes that interfere with transcriptional repression mediated by the Polycomb group of genes, we identified a dominant mutation affecting the Alhambra (Alh) gene, the fly homologue of the human AF10 gene. AF10 has been identified as a fusion partner of both MLL and CALM in infant leukemias. Both fusion proteins retain the leucine zipper domain of AF10 but not its PHD domain. We show here that, while the full-length ALH protein has no activity on Polycomb group-responsive elements (PREs), overexpression of the isolated ALH leucine zipper domain activates several PREs. Within the ALH full-length protein, the PHD domain inhibits the PRE deregulation mediated by the leucine zipper domain. This deregulation is conserved in the human AF10 leucine zipper domain, which confers the same activity on an oncogenic MLL-AF10 fusion protein expressed in Drosophila melanogaster. These data reveal new properties for the leucine zipper domain and thus might provide new clues to understanding the mechanisms by which AF10 fusion proteins in which the PHD domain is lost might trigger leukemias in humans. [ABSTRACT FROM AUTHOR]

Hypothyroidism in adults can manifest as myopathy. Often, other features of hypothyroidism are associated with it. But rarely, it can only present as muscle pseudohypertrophy along with cramps and weakness: a condition called Hoffman's Syndrome. This shows high elevation of muscle enzymes and myopathy patterns on electromyography. This condition responds very well to thyroxin replacement. The reporting of Hoffman's Syndrome is very are from Indian subcontinent, and probably this is the fist case from eastern India. [ABSTRACT FROM AUTHOR]

Development of organ-specific size and shape demands tight coordination between tissue growth and cell-cell adhesion. Dynamic regulation of cell adhesion proteins thus plays an important role during organogenesis. In Drosophila, the homophilic cell adhesion protein DE-Cadherin (DE-Cad) regulates epithelial cell-cell adhesion at adherens junctions (AJs). Here, we show that along the proximodistal (PD) axis of the developing wing epithelium, apical cell shapes and expression of DE-Cad are graded in response to Wingless (Wg), a morphogen secreted from the dorsoventral (DV) organizer in distal wing, suggesting a PD gradient of cell-cell adhesion. The Fat (Ft) tumor suppressor, by contrast, represses DE-Cad expression. In genetic tests, ft behaves as a suppressor of Wg signaling. Cytoplasmic pool of {beta}-catenin/Arm, the intracellular transducer of Wg signaling, is negatively correlated with the activity of Ft. Moreover, unlike that of Wg, signaling by Ft negatively regulates the expression of Distalless (Dll) and Vestigial (Vg). Finally, we show that Ft intersects Wnt/Wg signaling, downstream of the Wg ligand. Fat and Wg signaling thus exert opposing regulation to coordinate cell-cell adhesion and patterning along the PD axis of Drosophila wing. [ABSTRACT FROM AUTHOR]

Comments on the article on the collective nomenclature for LAP proteins, published in a 1996 issue of 'Nature Cell Biology.' Structure of LAP proteins; Number of leucine-rich repeats comprising LAP proteins.

During tissue closures, such as embryonic dorsal closure in Drosophila melanogaster, a proximate extra-embryonic layer, amnioserosa, generates forces that drive migration of the flanking lateral embryonic epidermis, thereby zip-shutting the embryo. Arguably, this paradigm of tissue closure is also recapitulated in mammalian wound healing wherein proximate fibroblasts transform into contractile myofibroblasts, develop cell junctions, and form a tissue layer de novo: contraction of the latter then aids in wound closure. Given this parallelism between disparate exemplars, we posit a general principle of tissue closure via proximate cell layer-generated forces. Here, we have tested this hypothesis in pupal thorax closure wherein 2 halves of the presumptive adult thorax of Drosophila, the contralateral heminotal epithelia, migrate over an underlying larval epidermal cell layer. We show that the proximate larval epidermal cell layer promotes thorax closure by its active contraction, orchestrated by its elaborate actomyosin network-driven epithelial cell dynamics, cell delamination, and death--the latter being prefigured by the activation of caspases. Larval epidermal cell dynamics generate contraction forces, which when relayed to the flanking heminota--via their mutual integrin-based adhesions--mediate thorax closure. Compromising any of these contraction forcegenerating mechanisms in the larval epidermal cell layer slows down heminotal migration, while loss of its relay to the flanking heminota abrogates the thorax closure altogether. Mathematical modeling further reconciles the biophysical underpinning of this emergent mechanism of thorax closure. Revealing mechanism of thorax closure apart, these findings show conservation of an essential principle of a proximate cell layer-driven tissue closure. [ABSTRACT FROM AUTHOR]

Conservation of genetic toolkits in disparate phyla may help reveal commonalities in organ designs transcending their extreme anatomical disparities. A male accessory sexual organ in mammals, the prostate, for instance, is anatomically disparate from its analogous, phylogenetically distant counterpart - the male accessory gland (MAG) - in insects like Drosophila. It has not been ascertained if the anatomically disparate Drosophila MAG shares developmental parallels with those of the mammalian prostate. Here we show that the development of Drosophila mesoderm-derived MAG entails recruitment of similar genetic toolkits of tubular organs like that seen in endoderm-derived mammalian prostate. For instance, like mammalian prostate, Drosophila MAG morphogenesis is marked by recruitment of fibroblast growth factor receptor (FGFR) - a signalling pathway often seen recruited for tubulogenesis - starting early during its adepithelial genesis. A specialisation of the individual domains of the developing MAG tube, on the other hand, is marked by the expression of a posterior Hox gene transcription factor, Abd-B, while Hh-Dpp signalling marks its growth. Drosophila MAG, therefore, reveals the developmental design of a unitary bud-derived tube that appears to have been co-opted for the development of male accessory sexual organs across distant phylogeny and embryonic lineages. This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Peptide therapeutics, unlike small-molecule drugs, display crucial advantages of target specificity and the ability to block large interacting interfaces, such as those of transcription factors. The transcription co-factor of the Hippo pathway, YAP/Yorkie (Yki), has been implicated in many cancers, and is dependent on its interaction with the DNA-binding TEAD/Sd proteins via a large Ω-loop. In addition, the mammalian vestigial-like (VGLL) proteins, specifically their TONDU domain, competitively inhibit YAP-TEAD interaction, resulting in arrest of tumor growth. Here, we show that overexpression of the TONDU peptide or its oral uptake leads to suppression of Yki-driven intestinal stem cell tumors in the adult Drosophila midgut. In addition, comparative proteomic analyses of peptide-treated and untreated tumors, together with chromatin immunoprecipitation analysis, reveal that integrin pathway members are part of the Yki-oncogenic network. Collectively, our findings establish Drosophila as a reliable in vivo platform to screen for cancer oral therapeutic peptides and reveal a tumor suppressive role for integrins in Yki-driven tumors.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Spatiotemporal changes in epithelial cell sizes-or epithelial cell size dynamics (ECD)-during morphogenesis entail interplay between two opposing forces: cell contraction via actomyosin cytoskeleton and cell expansion via cell-cell adhesion. Cell-cell adhesion-based ECD, however, has not yet been clearly demonstrated. For instance, changing levels of homophilic E-cadherin-based cell-cell adhesion induce cell sorting, but not ECD. Here we show that cell-expansive forces of heterophilic cell-cell adhesion regulate ECD: higher cell-cell adhesion results in cell size enlargement. Thus, ECD during morphogenesis in the heminotal epithelia of Drosophila pupae leading to thorax closure corresponds with spatiotemporal gradients of two heterophilic atypical cadherins-Fat (Ft) and Dachsous (Ds)-and the levels of Ft-Ds heterodimers formed concomitantly. Our mathematical modeling and genetic tests validate this mechanism of dynamic heterophilic cell-cell adhesion-based regulation of ECD. Conservation of these atypical cadherins suggests a wider prevalence of heterophilic cell-cell adhesion-based ECD regulation during animal morphogenesis.

During animal development, selector genes determine identities of body segments and those of individual organs. Selector genes are also misexpressed in cancers, although their contributions to tumor progression per se remain poorly understood. Using a model of cooperative tumorigenesis, we show that gain of selector genes results in tumor cooperation, but in only select developmental domains of the wing, haltere and eye-antennal imaginal discs of Drosophila larva. Thus, the field selector, Eyeless (Ey), and the segment selector, Ultrabithorax (Ubx), readily cooperate to bring about neoplastic transformation of cells displaying somatic loss of the tumor suppressor, Lgl, but in only those developmental domains that express the homeo-box protein, Homothorax (Hth), and/or the Zinc-finger protein, Teashirt (Tsh). In non-Hth/Tsh-expressing domains of these imaginal discs, however, gain of Ey in lgl - somatic clones induces neoplastic transformation in the distal wing disc and haltere, but not in the eye imaginal disc. Likewise, gain of Ubx in lgl - somatic clones induces transformation in the eye imaginal disc but not in its endogenous domain, namely, the haltere imaginal disc. Our results reveal that selector genes could behave as tumor drivers or inhibitors depending on the tissue contexts of their gains., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

Introduction: Cardiac autonomic neuropathy (CAN) is an important complication of type 2 diabetes mellitus (T2DM). Accelerated atherosclerosis is also common in T2DM. Carotid intima media thickness (CIMT) is a surrogate marker of atherosclerosis. We conducted a study to assess the CIMT in T2DM patients with CAN., Methods: In 84 T2DM patients cardiac autonomic function was assessed by five clinical tests including: 1) heart rate variation during deep breathing, 2) hear rate response to standing, 3) Valsalva ratio, 4) postural fall in systolic blood pressure (BP) three minutes after standing, and 5) resting heart rate. CAN was defined as two or more positive tests out of five for cardiac autonomic function. CIMT was measured by two dimensional (2D) ultrasound. We also examined for presence of any atherosclerotic plaque over intima of carotid artery as well as within the carotid bulb., Results: Thirty six (42.85 percent) out of 84 patients were detected to have CAN. CAN was significantly associated with duration of disease after its detection (P = 0.0253), high LDL cholesterol (P = 0.0418), low HDL cholesterol (P = 0.0001), fasting blood sugar (FBS) level (P = 0.0012) and CIMT (P = 0.0001) equal to or more than 69 mm., Conclusion: Increased CIMT equal to or more than 69 mm is associated with high occurrence of CAN in diabetic population. Duration of diabetes, abnormal lipid tests and FBS level significantly influence the development of CAN.

Endomyocardial fibrosis is a variety of restrictive cardiomyopathy, in which endocardium of one or both ventricles is thickened markedly with involvement of underlying myocardium. Partial obliteration of ventricular cavities by fibrous tissue and thrombus causes diastolic dysfunction with increased resistance to ventricular filling. Systolic function is well preserved till late stages. Biventricular or isolated left ventricular involvement is common. Isolated right ventricular involvement is relatively uncommon. Case reports on endomyocardial fibrosis have declined in literature. In India, endomyocardial fibrosis is mainly reported from Kerala. A case of right ventricular endomyocardial fibrosis from West Bengal is reported here. Isolated right sided endomyocardial fibrosis, massive right atrial enlargement, complete disorganization of tricuspid valve, massive pericardial effusion, normal absolute eosinophil count and its sporadic occurrence outside 15 degrees of the equatorial belt were interesting features in this case of endomyocardial fibrosis. X-ray features were typical of pericardial effusion masking underlying endomyocardial fibrosis. Endomyocardial fibrosis is a neglected research field. It needs more attention from biomedical researchers.

Background: C-reactive protein (CRP) is useful as marker of severity in malaria. African studies have shown that serum CRP levels correlate with parasite burden and complications in malaria, especially falciparum. However, there are very few data on CRP levels in Indian malaria patients., Materials and Methods: We assessed CRP levels in malaria patients at presentation and studied for any relation of CRP levels with subsequent prognosis. Statistical tests included student's t-test, Mann Whitney U test, and chi square test, all with 2-tailed analyzes., Results: Of 71 patients in our study, 42 (59.1%) were infected with P. falciparum. 23 (32.4%) patients needed admission and 10 (14.1%) died. Average CRP levels were quite high in malaria patients (31.29 ± 20.4 mg/L). There was no significant difference in CRP between vivax and falciparum cases. Admitted patients had significantly higher CRP levels compared to those treated on outdoor basis (47.11 ± 19.13 vs. 23.71 ± 16.35 mg/L; P < 0.0001). 8 patients were admitted with multiple complications. They had significantly high CRP level compared to those with 1 complication (P = 0.015). Also, patients who died had higher CRP levels compared to survivors (P = 0.000346). CRP levels at presentation showed positive correlation with duration of hospital stay (r = 0.59; P < 0.05). CRP levels >35 mg/L was highly sensitive in predicting mortality., Conclusion: Our study in Indian population corroborates the findings in African studies regarding prognostic role of CRP in malaria. CRP is an effective biomarker in assessing malaria severity and also for follow-up.

Proximal renal tubular acidosis (pRTA) is a rare disorder. Hypokalemia may be associated with it; occasionally leading to features like hypokalemic periodic paralysis. Though pRTA is a tubulointerstitial kidney disease, glomerulonephritis may occasionally lead to pRTA by tubular damage through leaking proteins, cytokines or by inflammatory infiltrates. In our reported case a 27 year old male had recurrent episodes of hypokalemic quadriparesis. Investigations revealed features of pRTA including hypokalemia and non-anion-gap hyperchloremic metabolic acidosis. His urine pH dropped to 5 with NH4Cl loading test. Kidney biopsy showed membranoproliferative glomerulonephritis with tubulointerstitial damage. Hypokalemic periodic paralysis and pRTA are uncommon associations of membranoproliferative glomerulonephritis.

Occurrence of glomerular diseases in psoriasis is rare, although the number of reports is increasing in recent years. Different types of glomerular involvement have been reported but mesangioproliferative glomerulonephritis with IgA deposits, AA amyloidosis and membranous nephropathy are relatively common in association with psoriasis. The term 'psoriatic nephropathy' has been introduced recently. We contribute a case to the ongoing discussin regarding psoriatic nephropathy. Our patient had mesangio-proliferative glomerulonephritis (with IgG and C3 deposition) in association with annular psoriasis (rare variety of chronic plaque psoriasis). Presence of messangio-proliferative glomerulonephritis with IgG deposition is rare in association with psoriasis. The patient responded well to weekly methotrexate (15 mg) injection. Methotrexate has not been tried previously in psoriatic nephropathy or reported to be effective in it.