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During homeostasis, a critical balance is maintained between myeloid-like progenitors and their differentiated progeny, which function to mitigate stress and innate immune challenges. The molecular mechanisms that help achieve this balance are not fully understood. Using genetic dissection in Drosophila, we show that a Wnt6/EGFR-signaling network simultaneously controls progenitor growth, proliferation, and differentiation. Unlike G1-quiescence of stem cells, hematopoietic progenitors are blocked in G2 phase by a β-catenin-independent (Wnt/STOP) Wnt6 pathway that restricts Cdc25 nuclear entry and promotes cell growth. Canonical β-catenin-dependent Wnt6 signaling is spatially confined to mature progenitors through localized activation of the tyrosine kinases EGFR and Abelson kinase (Abl), which promote nuclear entry of β-catenin and facilitate exit from G2. This strategy combines transcription-dependent and -independent forms of both Wnt6 and EGFR pathways to create a direct link between cell-cycle control and differentiation. This unique combinatorial strategy employing conserved components may underlie homeostatic balance and stress response in mammalian hematopoiesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Phagocytic macrophages are crucial for innate immunity and tissue homeostasis. Most tissue-resident macrophages develop from embryonic precursors that populate every organ before birth to lifelong self-renew. However, the mechanisms for versatile macrophage differentiation remain unknown. Here, we use in vivo genetic and cell biological analysis of the Drosophila larval hematopoietic organ, the lymph gland that produces macrophages. We show that the developmentally regulated transient activation of caspase-activated DNase (CAD)-mediated DNA strand breaks in intermediate progenitors is essential for macrophage differentiation. Insulin receptor-mediated PI3K/Akt signaling regulates the apoptosis signal-regulating kinase 1 (Ask1)/c-Jun kinase (JNK) axis to control sublethal levels of caspase activation, causing DNA strand breaks during macrophage development. Furthermore, caspase activity is also required for embryonic-origin macrophage development and efficient phagocytosis. Our study provides insights into developmental signaling and CAD-mediated DNA strand breaks associated with multifunctional and heterogeneous macrophage differentiation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Histoplasmosis is a systemic mycosis caused by  Histoplasma capsulatum  ( H. capsulatum ). Systemic involvement of histoplasmosis usually occurs in immune-compromised patients, patients with AIDS, or those taking immunosuppressive therapy. The present study aims to describe the clinical and laboratory characteristics and treatment outcome of histoplasmosis as the diagnosis is challenging and management protocol differs., Method: This retrospective study was done using a data registry at the medicine department of Dhaka Medical College Hospital. Here, patients received the standard treatment of histoplasmosis. Here, patients received the standard treatment of histoplasmosis, and clinical outcome was assessed at 3 months following starting standard treatment., Result: A total of nine patients were enrolled, six (66.7%) had systemic histoplasmosis. Three were poultry workers, and the most common comorbidity was diabetes 3 (33.3%). Fever 7 (77.7%), weight loss 6 (66.7%), hyperpigmentation 5 (55.5%), cough 4 (44.4%), oral ulceration 4 (44.4%), lymphadenopathy 4 (44.4%), and hypotension 3 (33.3%) were the most common clinical presentations. Seven (77.7%) out of nine patients were cured of histoplasmosis; however, one died before initiating antifungal medications and another one died due to a hypersensitivity reaction to liposomal amphotericin B.  Conclusion: For local histoplasmosis, oral itraconazole is an effective antifungal medication. However, in disseminated Histoplasmosis, liposomal amphotericin B followed by oral itraconazole is still one of the preferable and effective treatment options. Clinicians should be aware of hypersensitivity reactions of liposomal amphotericin B and its management before giving an infusion., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Been Sayeed et al.)

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)

The study was carried out to determine the role of plasma fibrinogen in diagnosis of neonatal sepsis and to evaluate its role in predicting short term outcome. Sixty five neonates with clinical features suggestive of neonatal sepsis were included in this study. Seventy five neonates served as the control group. Plasma fibrinogen, prothrombin time, activated partial thromboplastin time and platelet counts were performed in all the neonates. Cut-off value of plasma fibrinogen for diagnosis of neonatal sepsis was determined with the help of receiver operating characteristic curve. Plasma fibrinogen level was found to be significantly higher among neonates with sepsis when compared to neonates in control group ( p  < 0.0001). It had sensitivity of 70.8 %, specificity of 82.7 %, positive predictive value (PPV) of 72.3 % and negative predictive value (NPV) of 81.6 % for diagnosis of neonatal sepsis at cut-off value of 301.90 mg/dL. When neonates with septic shock and/or disseminated intravascular coagulation (DIC) were excluded from study population, sensitivity and NPV rose to 91.9 % and 95.4 % at the same cut-off value while specificity and PPV remained the same. Lower level of plasma fibrinogen was detected in neonates with septic shock and/or DIC ( p  < 0.0001) and in neonates who died ( p  < 0.0001). Hence plasma fibrinogen can serve as an effective tool in diagnostic work up of neonatal sepsis as well as in assessing development of complications and outcome.

Objectives: Magnesium historically has been used for treatment and/or prevention of eclampsia. Considering the low body mass index of Indian women, a low-dose magnesium sulfate regime has been introduced by some authors. Increased blood levels of magnesium in neonates is associated with increased still birth, early neonatal death, birth asphyxia, bradycardia, hypotonia, gastrointestinal hypomotility. The objective of this study was to assess safety of low-dose magnesium sulfate regimen in neonates of eclamptic mothers treated with this regimen., Materials and Methods: This was a cross-sectional observational study of 100 eclampsia patients and their neonates. Loading dose and maintenance doses of magnesium sulfate were administered to patients by combination of intravenous and intramuscular routes. Maternal serum and cord blood magnesium levels were estimated. Neonatal outcome was assessed., Results: Bradycardia was observed in 18 (19.15%) of the neonates, 16 (17.02%) of the neonates were diagnosed with hypotonia. Pearson Correlation Coefficient showed Apgar scores decreased with increase in cord blood magnesium levels. Unpaired t-test showed lower Apgar scores with increasing dose of magnesium sulfate. The Chi-square/Fisher's exact test showed significant increase in hypotonia, birth asphyxia, intubation in delivery room, Neonatal Intensive Care Unit (NICU) care requirement, with increasing dose of magnesium sulfate. (P ≤ 0.05)., Conclusion: Several neonatal complications are significantly related to increasing serum magnesium levels. Overall, the low-dose magnesium sulfate regimen was safe in the management of eclamptic mothers, without toxicity to their neonates.

Aim: The aim was to study the effect of Aloe vera and clove powder supplementation on carcass characteristics, composition and serum enzymes of Japanese quails., Materials and Methods: The study was conducted on 120-day-old Japanese quails, which were randomly divided into four treatment groups viz. T1-control, T2-0.5% A. vera, T3-0.5% clove, and T4-(0.25% A. vera + 0.25% clove) powder, each having three replications consisting of ten Japanese quails. The birds in control group (T1) were fed no supplement whereas in treatments T2-T4 birds were supplemented with A. vera leaf powder, clove, and mixture of both (powdered form) at 0.5, 0.5, and 0.25+0.25% of feed, respectively. After 7 days of brooding, a feeding trial of 35 days was conducted. On 35(th) day of trial birds were sacrificed and dressing percentage, cut up parts, organ weight, processing losses and carcass meat composition of the breast, thigh, and drumstick were recorded. Blood samples were collected on the same day and serum was separated to evaluate serum enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST)., Results: It showed significantly (p<0.05) higher values of dressing percentage with and without giblet and breast weight in the T2-T4 group as compared to the T1 group. No significant (p>0.05) differences were observed in giblet weight, other cut up parts and composition of the breast, thigh, and drumstick muscles in all the treatment groups. Serum ALT and AST did not vary significantly among different treatment groups., Conclusion: A. vera and clove supplementation improved the dressing percentage and breast weight without adversely affecting the meat composition and serum enzymes. Thus, these can be used as a growth promoter in Japanese quails.

Blood progenitors within the lymph gland, a larval organ that supports hematopoiesis in Drosophila melanogaster, are maintained by integrating signals emanating from niche-like cells and those from differentiating blood cells. We term the signal from differentiating cells the 'equilibrium signal' in order to distinguish it from the 'niche signal'. Earlier we showed that equilibrium signaling utilizes Pvr (the Drosophila PDGF/VEGF receptor), STAT92E, and adenosine deaminase-related growth factor A (ADGF-A) (Mondal et al., 2011). Little is known about how this signal initiates during hematopoietic development. To identify new genes involved in lymph gland blood progenitor maintenance, particularly those involved in equilibrium signaling, we performed a genetic screen that identified bip1 (bric à brac interacting protein 1) and Nucleoporin 98 (Nup98) as additional regulators of the equilibrium signal. We show that the products of these genes along with the Bip1-interacting protein RpS8 (Ribosomal protein S8) are required for the proper expression of Pvr.

Drosophila hematopoietic progenitor maintenance involves both near neighbor and systemic interactions. This study shows that olfactory receptor neurons (ORNs) function upstream of a small set of neurosecretory cells that express GABA. Upon olfactory stimulation, GABA from these neurosecretory cells is secreted into the circulating hemolymph and binds to metabotropic GABAB receptors expressed on blood progenitors within the hematopoietic organ, the lymph gland. The resulting GABA signal causes high cytosolic Ca(2+), which is necessary and sufficient for progenitor maintenance. Thus, the activation of an odorant receptor is essential for blood progenitor maintenance, and consequently, larvae raised on minimal odor environments fail to sustain a pool of hematopoietic progenitors. This study links sensory perception and the effects of its deprivation on the integrity of the hematopoietic and innate immune systems in Drosophila. PAPERCLIP:, (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To compare the safety, efficacy and reliability of FARES (fast, reliable and safe) method with the Eachempati external rotation method for reduction of anterior dislocation of shoulder., Methods: In a single centre, prospective, randomised clinical trial, conducted in our institution from January 2010 to October 2011, 160 patients with acute anterior dislocation of shoulder (with or without an associated fracture of the greater tuberosity of the humerus) who satisfy the inclusion and exclusion criteria were enrolled in the study. Patients were randomised to receive reduction of dislocation with one of the two methods (FARES and Eachempati method) with 80 patients in each group, according to a table of random numbers. Following successful reduction, the following information was recorded: (i) intensity of pain perceived during reduction by using a visual analogue scale (VAS) ranging from 0 (no pain) to 100 (worst pain possible), (ii) time interval between the dislocation and the first attempt of reduction, (iii) time interval between the start of the reduction manoeuvre and completion of the reduction, (iv) number of attempts taken to complete the reduction and (iv) any post-reduction complications., Results: There were no significant differences between the two groups with regard to baseline characteristics. No post-reduction complications were noted in any of the patients in this study. Successful reduction of shoulder dislocation was achieved with the FARES method in 76 (95%) of 80 patients and with the Eachempati external rotation method in 73 (91.25%) of 80 patients. This difference was not statistically significant (p=0.53, Fisher's exact test). Post-reduction result analysis shows that there was a statistically significant difference between the two methods in favour of the FARES method in terms of speed of reduction, pain felt during reduction and number of attempts taken during reduction., Conclusions: FARES method, as compared with the Eachempati method, is significantly faster, less painful and less number of attempts required for reduction. As both the methods appeared to be safe and effective compared to the previous traditional techniques, we strongly recommend FARES method as the first-choice method compared to Eachempati method for reduction of acute anterior dislocation of shoulder., Level of Evidence: Therapeutic Level I., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To compare the efficacy of up to 3 epidural butorphanol plus corticosteroid with corticosteroid alone for sciatica due to herniated nucleus pulposus., Materials and Methods: In a randomized, double-blind controlled clinical trial, we administered up to 3 epidural injections of either 80 mg (2 mL) of methylprednisolone acetate and 1 mg (1 mL) of butorphanol diluted with 7 mL of isotonic saline or 80 mg (2 mL) of methylprednisolone acetate diluted with 8 mL of isotonic saline by a lumbar interlaminar approach under fluoroscopic guidance to 120 patients (60 patients in each group) with sciatica due to a herniated nucleus pulposus lasting for 4 weeks to 1 year. All patients had scores higher than 30 mm on visual analog scale (VAS). Information on the use of paracetamol, intensity of pain on a VAS ranging from 0 (no pain) to 100 mm (worst pain possible), Schober's test (cm), Straight Leg Raising test, neurologic examination assessing sensory deficits, motor deficits and reflex changes, and Oswestry Low Back Pain Disability Questionnaire were evaluated at 3 weeks, 6 weeks, and 3 months after the first injection., Results: There were no significant differences between the 2 groups with regard to baseline characteristics, withdrawals, and complication rate. Three weeks, 6 weeks, and 3 months after the first injection, all the outcome measures in the butorphanol plus corticosteroid group were significantly different from that of the corticosteroid group., Conclusions: Epidural butorphanol plus corticosteroid injections, as compared with corticosteroid alone injections, offered marked improvement in pain, reflex, motor and sensory deficits, and functional status and reduced the need for analgesics., Level of Evidence: Therapeutic Level I.

Maintenance of a hematopoietic progenitor population requires extensive interaction with cells within a microenvironment or niche. In the Drosophila hematopoietic organ, niche-derived Hedgehog signaling maintains the progenitor population. Here, we show that the hematopoietic progenitors also require a signal mediated by Adenosine deaminase growth factor A (Adgf-A) arising from differentiating cells that regulates extracellular levels of adenosine. The adenosine signal opposes the effects of Hedgehog signaling within the hematopoietic progenitor cells and the magnitude of the adenosine signal is kept in check by the level of Adgf-A secreted from differentiating cells. Our findings reveal signals arising from differentiating cells that are required for maintaining progenitor cell quiescence and that function with the niche-derived signal in maintaining the progenitor state. Similar homeostatic mechanisms are likely to be utilized in other systems that maintain relatively large numbers of progenitors that are not all in direct contact with the cells of the niche., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The FRAXA locus is flanked by three polymorphic STR markers DXS548, FRAXAC1, and FRAXAC2. Allele frequencies of these markers were determined on a population representing the eastern part of India comprising of 69 normal controls and 69 unrelated subjects with mental retardation, among whom 21 were fragile X patients. These frequencies were compared with published data on other Indian population and the major populations of the world. The allele and haplotype distribution of the studied population were significantly different in some respects from the major populations of the world. The increase of heterozygosities in fragile X samples (DXS548 67.5%, FRAXAC1 63.5%, FRAXAC2 68.5%) relative to the controls (DXS548 63.3%, FRAXAC1 51.0%, FRAXAC2 67.2%) suggests a multimodal distribution of fragile X associated alleles. Haplotype analyses with DXS548 and FRAXAC1 markers revealed that haplotype distribution in the normal controls and fragile X groups were significantly different, suggesting a weak founder effect., (Copyright 2008 Wiley-Liss, Inc.)

The objective of the paper was to study the association of polymorphisms of phases I and II xenobiotic metabolizing enzyme genes cytochrome P450 (CYP-4501A1*2A, *2B, *2C and *4 alleles, CYP-4502D6*4 allele), glutathione-S-transferase (GSTM1 and GSTT1 null genotypes) and N-acetyl transferase 2 (NAT2*6B and *7A alleles) with the incidence of acute myeloid leukemia (AML) in an eastern Indian population. Polymerase chain reaction and restriction fragment length polymorphism of genomic DNA from peripheral blood cells were used to detect CYP-450 and NAT2 gene polymorphisms in 110 AML patients and 144 racially and geographically matched normal controls. Polymerase chain reaction was also applied to detect GST gene polymorphisms in both groups. A statistically significant difference between the AML group and the normal group was observed in the case of glutathione-S-transferase M1 null (odds ratio 3.25, 95% confidence interval 1.9-5.58, P<0.001) and N-acetyl transferase 2*6B (odds ratio 3.04, 95% confidence interval 1.79-5.16, P<0.001) genotypes. Combined deficiency of N-acetyl transferase 2 and glutathione-S-transferase M1 genes produced an odds ratio of 11.91 (95% confidence interval 4.06-34.96, P<0.001). The effect of N-acetyl transferase 2*6B (P<0.001) is significant only at ages

Molecular breakpoint of the BCR-ABL fusion gene has been characterized for 122 chronic myeloid leukemia patients. Out of 122 cases, 33 b2a2, 69 b3a2, 2 e1a2, and 2 e19a2 cases have been detected. Six coexpressed both b2a2 and b3a2 transcripts. All the coexpressing samples had an A>G polymorphism at the putative splice branchpoint in intron 13. The T>C polymorphism in exon 13, reported to be linked to coexpression, was not present in all the coexpressing patients. No correlation of transcript type with platelet count was detected. Those expressing b2a2 transcript were diagnosed at relatively younger age and with higher white blood cell count, in agreement with other reports. However, the correlation was not statistically significant., ((c) 2006 Wiley-Liss, Inc.)

This report describes two patients with chronic myeloid leukaemia (CML): one of them developed accelerated phase CML and died 8 years after diagnosis and the other is at the chronic phase. Sequence analysis of reverse transcription-polymerase chain reaction products showed the presence of BCR-ABL fusion transcript e19a2. This finding suggests that CML carrying mu-BCR breakpoint may exhibit a clinical course similar to typical CML.

Objective: To correlate different polymorphisms of the beta-globin cluster with fetal hemoglobin (HbF) level in beta-thalassemia and E-beta thalassemia patients., Methods: Fifteen thalassemia patients, seven with high HbF and not requiring transfusion, eight with lower HbF and requiring transfusion were studied for beta-globin mutation, concurrent inheritance of alpha-thalassemia, RFLP haplotype, a C-->T polymorphism at -158 of Ggamma and configuration of an (AT)(x)T(y) motif at -540 of beta-globin gene., Results: Senegal 5'beta-haplotype and the polymorphism at -158 of G(gamma) was (P = 0.063) was linked to the high-HbF phenotype but the (AT)(9)T(5) configuration of the (AT)(x)T(y) motif was not (P = 0.6). Study of 30 chromosomes revealed 7 different configurations of the (AT)(x)T(y) motif. Association of these motifs with specific beta-globin mutations of this region has also been determined., Conclusion: The senegal haplotype and the polymorphism at -158 of G(gamma) was linked to the high-HbF phenotype., ((c) Blackwell Munksgaard 2005.)

Polymorphisms associated with genes coding for glutathione S-transferase enzymes are known to influence metabolism of different carcinogens and have been associated with incidence of various types of cancer. We have determined the GST M1 and GST T1 'null' genotype frequency in 81 patients with chronic myeloid leukaemia (CML) and 123 racially and geographically matched control individuals by multiplex polymerase chain reaction (PCR). GST M1 null genotype frequencies in CML and controls were 28.4% and 27.7%, respectively. GST T1 null genotype frequencies in CML and controls were 19.8% and 7.3%, respectively. The GST T1 null genotype frequency in CML patients is significantly different from that in controls (odds ratio (OR) 3.12, 95% confidence interval (CI) 1.3-7.45, P=0.008).

Objective: To control the birth of thalassemic children in India., Methods: Mutations present in the population of eastern India and in carrier parents seeking prenatal diagnosis were detected by the PCR-based technique of ARMS (amplification refractory mutation system) or gap-PCR. To screen for maternal tissue contamination in CVS, haplotypes associated with the beta-globin gene clusters were constructed using six polymorphic restriction sites. Prenatal diagnosis was accomplished by checking presence of parental mutation in the DNA from chorionic villus sampling (CVS) collected at 8 to 10 weeks' gestation by appropriate technique., Results: Six hundred and fifty (650) unrelated beta-thalassemia chromosomes were screened for 11 common mutations to characterize the mutation distribution in this population. Starting from early 2000, 63 families from different parts of West Bengal and from surrounding areas have been offered prenatal counseling for beta-thalassemia., Conclusion: The population of this region is conscious and willing to accept prenatal diagnosis as a means of control of thalassemia., (Copyright (c) 2004 John Wiley & Sons, Ltd.)

A polystyrene divinyl benzene (8%) copolymer has been functionalized by coupling it through NN group with 2-naphthol-3,6-disulfonic acid (NDSA). The resulting resin has been characterized by elemental analysis, thermogravimetric analysis and infrared spectra. The hydrogen ion, water regain and metal ion capacities of the resin have been determined. Two forms of chromium show different exchange capacities at different pH values, viz. Cr(III) selectively retained at pH 6.5 whereas Cr(VI) retained at pH 1.5. Hence complete separation of the two forms of chromium is possible. The kinetic studies show that the exchange of Cr(III) and Cr(VI) follows second-order kinetics. The metal ion concentration was measured by flame atomic absorption spectrometry. The method has been successfully applied for the speciation of chromium in natural water samples.

6-Mercapto purinylazo resin has been used as solid phase extractor. Based on solid phase extraction, the present work describes the preconcentration and determination of copper, zinc and cadmium in certified biological samples after microwave-assisted digestion. The exchange capacity of the resin, the sorption and desorption of metal ions, and the effect of diverse ions have also been determined. The results show that the resin is highly selective for determination of these biologically significant metals. The method is simple, rapid and free from interferences and can be used routinely.