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1.
Dose Response ; 22(2): 15593258241247185, 2024.
Article in English | MEDLINE | ID: mdl-38617389

ABSTRACT

Background: Caffeine citrate (CC)-induced excessive energy expenditure, diuresis, natriuresis, and other CC-associated potential side effects (CC-APSEs) result in lower daily weight gain (WG) in premature neonates. This study aimed to assess higher CC-doses' effect on the mean daily-WG (MD-WG) and CC-APSE development, considering 5 mg/kg/day as the standard regimen. Method: This retrospective cohort study included neonates of ≤36 weeks gestational age and received CC-therapy. The same participants were followed for data analysis in two postnatal phases: 15-28 and 29-42 days of life (DOL). Based on daily CC-dose, formed group-I=(5 mg/kg/day), group-II=(>5-7 mg/kg/day), and group-III=(>7 mg/kg/day). Data was analyzed separately for group-II and group-III using group-I as the standard. Results: The study included 284 neonates. During phase-I, the MD-WG was significantly higher in group-I than group-II (19.9 ± .88 g/kg/d vs 17.5 ± .49, P = .031) and group-III (19.9 ± .88 g/kg/d vs 16.7 ± .71, P < .001). During 29-42 DOL, the MD-WG of group-I was only significantly higher than group-III (21.5 ± .42 g/kg/d vs 18.1 ± .39 g/kg/d, P = .003) and comparable with group-II. During 15-28 DOL, CC-APSEs were significantly higher in group-II and group-III but during 29-42 DOL was significant only in group-III. Conclusion: Exposure to higher caffeine doses in this study cohort is associated with lower postnatal WG in preterm neonates than standard daily doses may be due to its catabolic effects and CC-APSEs.

2.
Sci Data ; 10(1): 214, 2023 04 17.
Article in English | MEDLINE | ID: mdl-37062771

ABSTRACT

The silver pride of Bangladesh, migratory shad, Tenualosa ilisha (Hilsa), makes the highest contribution to the total fish production of Bangladesh. Despite its noteworthy contribution, a well-annotated transcriptome data is not available. Here we report a transcriptomic catalog of Hilsa, constructed by assembling RNA-Seq reads from different tissues of the fish including brain, gill, kidney, liver, and muscle. Hilsa fish were collected from different aquatic habitats (fresh, brackish, and sea water) and the sequencing was performed in the next generation sequencing (NGS) platform. De novo assembly of the sequences obtained from 46 cDNA libraries revealed 462,085 transcript isoforms that were subsequently annotated using the Universal Protein Resource Knowledgebase (UniPortKB) as a reference. Starting from the sampling to final annotation, all the steps along with the workflow are reported here. This study will provide a significant resource for ongoing and future research on Hilsa for transcriptome based expression profiling and identification of candidate genes.


Subject(s)
Fishes , Transcriptome , Animals , Fishes/genetics , Gene Expression Profiling , Genetic Association Studies , Molecular Sequence Annotation , Protein Isoforms/genetics
3.
Cell Rep ; 42(4): 112377, 2023 04 25.
Article in English | MEDLINE | ID: mdl-37060563

ABSTRACT

The emergence of castration-resistant prostate cancer remains an area of unmet clinical need. We recently identified a subpopulation of normal prostate progenitor cells, characterized by an intrinsic resistance to androgen deprivation and expression of LY6D. We here demonstrate that conditional deletion of PTEN in the murine prostate epithelium causes an expansion of transformed LY6D+ progenitor cells without impairing stem cell properties. Transcriptomic analyses of LY6D+ luminal cells identified an autocrine positive feedback loop, based on the secretion of amphiregulin (AREG)-mediated activation of mitogen-activated protein kinase (MAPK) signaling, increasing cellular fitness and organoid formation. Pharmacological interference with this pathway overcomes the castration-resistant properties of LY6D+ cells with a suppression of organoid formation and loss of LY6D+ cells in vivo. Notably, LY6D+ tumor cells are enriched in high-grade and androgen-resistant prostate cancer, providing clinical evidence for their contribution to advanced disease. Our data indicate that early interference with MAPK inhibitors can prevent progression of castration-resistant prostate cancer.


Subject(s)
Androgens , Prostatic Neoplasms, Castration-Resistant , Animals , Male , Mice , Androgen Antagonists/pharmacology , Androgens/metabolism , Cell Adhesion Molecules/metabolism , Cell Line, Tumor , GPI-Linked Proteins/metabolism , Mitogen-Activated Protein Kinases/metabolism , Prostate/metabolism , Prostatic Neoplasms, Castration-Resistant/metabolism , Receptors, Androgen/metabolism
4.
Am J Cancer Res ; 13(1): 326-339, 2023.
Article in English | MEDLINE | ID: mdl-36777505

ABSTRACT

Advanced urothelial carcinoma continues to have a dismal prognosis despite several new therapies in the last 5 years. FGFR2 and FGFR3 mutations and fusions, PD-L1 expression, tumor mutational burden, and microsatellite instability are established predictive biomarkers in advanced urothelial carcinoma. Novel biomarkers can optimize the sequencing of available treatments and improve outcomes. We describe herein the clinical and pathologic features of patients with an emerging subtype of bladder cancer characterized by deletion of the gene MTAP encoding the enzyme S-Methyl-5'-thioadenosine phosphatase, a potential biomarker of response to pemetrexed. We performed a retrospective analysis of 61 patients with advanced urothelial carcinoma for whom demographics, pathologic specimens, next generation sequencing, and clinical outcomes were available. We compared the frequency of histology variants, upper tract location, pathogenic gene variants, tumor response, progression free survival (PFS) and overall survival (OS) between patients with tumors harboring MTAP deletion (MTAP-del) and wild type tumors (MTAP-WT). A propensity score matching of 5 covariates (age, gender, presence of variant histology, prior surgery, and prior non-muscle invasive bladder cancer) was calculated to compensate for disparity when comparing survival in these subgroups. Non-supervised clustering analysis of differentially expressed genes between MTAP-del and MTAP-WT urothelial carcinomas was performed. MTAP-del occurred in 19 patients (31%). Tumors with MTAP-del were characterized by higher prevalence of squamous differentiation (47.4 vs 11.9%), bone metastases (52.6 vs 23.5%) and lower frequency of upper urinary tract location (5.2% vs 26.1%). Pathway gene set enrichment analysis showed that among the genes upregulated in the MTAP-del cohort, at least 5 were linked to keratinization (FOXN1, KRT33A/B, KRT84, RPTN) possibly contributing to the higher prevalence of squamous differentiation. Alterations in the PIK3 and MAPK pathways were more frequent when MTAP was deleted. There was a trend to inferior response to chemotherapy among MTAP-del tumors, but no difference in the response to immune checkpoint inhibitors or enfortumab. Median progression free survival after first line therapy (PFS1) was 5.5 months for patients with MTAP-WT and 4.5 months for patients with MTAP-del (HR = 1.30; 95% CI, 0.64-2.63; P = 0.471). There was no difference in the time from metastatic diagnosis to death (P = 0.6346). Median OS from diagnosis of localized or de novo metastatic disease was 16 months (range 1.5-60, IQR 8-26) for patients with MTAP-del and 24.5 months (range 3-156, IQR 16-48) for patients with MTAP-WT (P = 0.0218), suggesting that time to progression to metastatic disease is shorter in MTAP-del patients. Covariates did not impact significantly overall survival on propensity score matching. In conclusion, MTAP -del occurs in approximately 30% of patients with advanced urothelial carcinoma and defines a subgroup of patients with aggressive features, such as squamous differentiation, frequent bone metastases, poor response to chemotherapy, and shorter time to progression to metastatic disease.

5.
J Dent (Shiraz) ; 23(3): 266-271, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36506878

ABSTRACT

Statement of the Problem: Iron overload in ß-thalassemia major leads to oxidative damage to tissues, which may have an important role in the onset and progression of oral diseases. Purpose: The aim of this study was to evaluate the salivary oxidative stress indicators, total protein, iron, and pH in children with ß-thalassemia major and their relationship with the status of dental caries in comparison with healthy children. Materials and Method: In this case-control study, 68 ß-thalassemia major and healthy children, who were age- and sex matched, were selected. Two mililiters of saliva was collected from each child. The pH was measured using pH meter paper. Thiobarbituric acid reactive substances (TBARS) as salivary lipid peroxidation index, total antioxidant capacity (TAC), total protein, and iron were measured by spectrophotometry. Data were analyzed by SPSS ver. 22 software with Pearson and independent samples t-test. Results: TBARS, TAC, iron and dmft index in the ß-thalassemia major group were significantly higher and pH was significantly lower than the control group (p< 0.001). The total protein difference between the two groups was not significant (p= 0.081). Conclusion: Considering the higher salivary TBARS in the ß-thalassemia major group, oxidative stress can be considered as a risk factor for dental caries in children with ß-thalassemia major. Prescription of antioxidant supplements especially natural antioxidants in the diet of children with ß-thalassemia major is recommended to reduce oxidative stress.

6.
PLoS One ; 17(11): e0275655, 2022.
Article in English | MEDLINE | ID: mdl-36350877

ABSTRACT

BACKGROUND: Caffeine is available in an ampoule, used via parenteral and enteral routes in preterm neonates to treat apnea of prematurity (AOP) in neonates of gestational age ≥ 35-40 weeks. A longer duration of therapy has a higher risk of medication non-adherence due to higher costs and inappropriate dosage forms. Pharmaceutically compounded oral caffeine (PCC) could be an appropriate alternate dosage form. The researchers aimed to determine the impact of PCC on medication-related factors influencing medication adherence (MA) and the frequency of hospital readmission with apnea (HRA) in preterm neonates. METHODS: We conducted a single-center quasi-experimental study for this quality improvement project using PCC among the preterm neonates admitted in a tertiary care level-III NICU at the Aga Khan University Hospital Karachi, Pakistan, received caffeine therapy, and survived at discharge. The researchers compared pre-PCC data (April-December 2017) with post-PCC data (April-Dec 2018) each for nine months, with three months intervals (January-March 2018) of PCC formulation and implementation phase. The study was conducted according to the SQUIRE2.0 guidelines. The Data were collated on factors influencing MA, including the cost of therapy, medication refill rates, and parental complaints as primary outcome measures. The Risk factors of HRA were included as secondary outcomes. RESULTS: After PCC implementation cost of therapy was reduced significantly from Rs. 97000.0 (729.0 USD) to Rs. 24500.0 (185.0 USD) (p<0.001), significantly higher (p<0.001) number of patients completed remaining refills (77.6% pre-phase vs 97.5% post-phase). The number of parental complaints about cost, ampoule usage, medication drawing issue, wastage, inappropriate dosage form, and longer duration of therapy reduced significantly in post-phase. HRA reduced from 25% to 6.6% (p<0.001). Post-implementation of PCC (RR 0.14; 95% CI: 0.07-0.27) was a significant independent risk factor for reducing HRA using a multivariate analysis model. Longer duration of caffeine therapy after discharge (RR 1.05; 95% CI: 1.04-1.04), those who were born in multiple births (RR 1.15; 95% CI: 1.15-1.15), and those who had higher number of siblings were other significant independent risk factors for HRA. CONCLUSIONS: PCC dispensation in the appropriate dosage form at discharge effectively reduced cost, non-adherence to therapy, and risk of hospital readmissions. This neonatal clinical and compounding pharmacist-led model can be replicated in other resource-limiting setting.


Subject(s)
Apnea , Caffeine , Infant, Newborn , Humans , Infant , Caffeine/therapeutic use , Apnea/drug therapy , Patient Readmission , Gestational Age , Medication Adherence
7.
J Ayub Med Coll Abbottabad ; 34(3): 582-584, 2022.
Article in English | MEDLINE | ID: mdl-36377181

ABSTRACT

Acute appendicitis is an infrequent condition in neonates, especially in term infants. With around 100 cases in the last century and no specific diagnostic tool, this case report is an addition to the existing literature that helps in our understanding of the disease. A preterm infant who had greenish aspirates and dilated bowel loops on abdominal x ray and was treated on the lines of necrotizing enterocolitis failed to improve. Baby had issues of abdominal distension whenever feeds were started hence exploratory laparotomy was done on the 45th day of life which showed appendicitis with adherent terminal ileum, caecum, and appendix. Two months after the surgery, the patient was unable to respond to antibiotic therapy for septic condition leading to death.


Subject(s)
Appendicitis , Enterocolitis, Necrotizing , Humans , Infant, Newborn , Infant , Appendicitis/diagnosis , Appendicitis/surgery , Enterocolitis, Necrotizing/diagnosis , Enterocolitis, Necrotizing/surgery , Infant, Premature , Laparotomy/adverse effects , Acute Disease
8.
J Clin Lab Anal ; 36(9): e24664, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36082467

ABSTRACT

BACKGROUND: The most frequent species of Candida to infect and colonize patients with neutropenia is still Candida albicans. This study aimed to provide detailed information on the phenotype, genotype, and mating type of oral C. albicans isolated from neutropenic pediatric patients, and to investigate how these characteristics are related. METHODS: Two hundred fifty-four oral samples from patients under 18 years old with neutropenia and malignancies were collected from January to October 2021. Samples were cultured on CHROMagar Candida. Isolates of C. albicans were identified with the germ tube test, chlamydospore production on cornmeal agar, and PCR-RFLP. Genotyping of C. albicans isolates was carried out by amplifying the 25S rDNA gene with specific CAINT-L and CA-INT-R primers. MTLa1 and MTLα1 primers were used to identify each mating type. Yeast peptone dextrose supplemented with phloxine B was used to identify different phenotypes. RESULTS: Ninety-two (36%) patients were positive for C. albicans. The mean age of patients was 7.85. Fifty-three (58.9%) isolates demonstrated type A, 15 (16.7%) type B, 15 (16.7%) types D/E, and 7 (7.7%) type C. Three isolates each (3.3%) were homozygous for MTLa or homozygous for MTLα. All of the MTL-homozygous isolates were genotype A. There was a significant correlation between patients' underlying disease and genotype (p = 0.036). There was a significant correlation between mating type and genotype (p = 0.000). CONCLUSION: Most of the isolates exhibited a white phenotype, noted in the literature as the most virulent. Moreover, heterozygous strains were frequent and may play a role in Candida colonization.


Subject(s)
Candida albicans , Neutropenia , Candida/genetics , Candida albicans/genetics , DNA Primers , Genotype , Humans , Phenotype
9.
Microb Pathog ; 170: 105690, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35917988

ABSTRACT

BACKGROUND: Candida tropicalis is one of the most frequently isolated species and is commonly associated with nosocomial infections, hematological malignancy, neutropenia, and urinary tract infections. AIMS: This study aims to genotype C. tropicalis strains isolated from pediatric patients admitted to two hospitals in Ahvaz, Iran. We provide a vision of the genotypes, mating types, enzymatic activity, phenotypes, and antifungal susceptibility profile of these isolates. METHODS: Candida tropicalis isolates were collected from various clinical (Oral, urine, wound, and bronchoalveolar lavage) and environmental sources between November 2020 and November 2021. Primitively, samples were cultured on CHROMagar Candida. All isolates were identified by sequencing the Internal Transcribed Spacer (ITS) region for precise identification. Isolates were genotyped by six microsatellite markers specific for C. tropicalis. Antifungal susceptibility profiles were determined against eight antifungal agents according to CLSI M27 standards. The phenotype of each C. tropicalis isolate was assessed using yeast peptone dextrose agar supplemented with phloxine B. Mating types of C. tropicalis isolates were determined using MTLa1 and MTL2 specific primers. RESULTS: Species identification revealed 46 C. tropicalis strains. Among them, 39 different genotypes were detected that have split into 34 singletons and five clusters. Twenty isolates were the non-wild type for itraconazole and posaconazole. Four isolates were multidrug-resistant. The activity of hemolysin and esterase enzyme was very strong among all isolates. Mating type and phenotype were not significantly correlated with genotypes (p = 0.721 and p = 0.135, respectively). CONCLUSIONS: To conclude, tested populations were moderately differentiated with high gene flow. One cluster of isolates among different hospitals was identified, and three clusters were from different cities.


Subject(s)
Antifungal Agents , Candida tropicalis , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Candida , Drug Resistance, Fungal , Humans , Microbial Sensitivity Tests , Phenotype
10.
BMC Pediatr ; 22(1): 437, 2022 07 21.
Article in English | MEDLINE | ID: mdl-35864501

ABSTRACT

BACKGROUND: Caffeine is a routinely prescribed pharmacological active compound in neonatal intensive care units (NICU) for treating apnea of prematurity (AOP), which also decreases the risk of bronchopulmonary dysplasia and cerebral palsy in neonates. Caffeine-induced excessive calcium loss can promote the development of metabolic bone disease (MBD) in preterm neonates. This study aimed to evaluate the effect of the caffeine regimen on the development of osteopenia of prematurity (OOP), using serum alkaline phosphatase (serum-ALP) concentrations as a surrogate marker at the 4th week of life. METHODS: This retrospective cohort study was conducted including neonates of < 32 weeks gestational age (GA) and birth weight < 1500 g, admitted to NICU from April-2017 to December-2018 and received caffeine therapy till 28 days of life for AOP. Based on serum-ALP levels, formed the high and low-ALP groups. Neonatal characteristics, caffeine regimen, risk factors for OOP, including duration of parenteral nutrition (PN), exposure to medicines associated with MBD, and intake of essential vitamins and minerals, were compared in both groups. Predictors of OOP were analyzed through logistic regression. RESULTS: From the total of 268 participants, 52 (19%) developed OOP, mostly female (61.5%). In the high ALP group, the serum-ALP levels were significantly higher than in the low-ALP group (725.0 ± 143.8 vs 273.6 ± 55.0 units/L, p < 0.001). The high-ALP group received significantly (p < 0.001) higher daily and cumulative caffeine doses and were associated with a higher likelihood of developing OOP in this study cohort [cumulative dose (mg) (AOR = 1.082 95% CI 1.011 to 1.157) and daily dose (mg/kg/day) (AOR = 2.892 95% CI 1.392 to 6.007)]. Smaller GA was found directly related to OOP. Among the other medical risk factors, phosphorus intake was significantly low in the high-ALP group. No, significant relationship between duration of PN and use of steroids and diuretics, and intake of vitamins and minerals were identified. CONCLUSION: The daily and cumulative doses of caffeine and smaller GA are associated with the development of OOP in this study cohort. Clinical randomized control studies are needed to validate the outcomes and determine the range of safest and most effective caffeine doses for treating AOP in preterm neonates.


Subject(s)
Bone Diseases, Metabolic , Rickets , Sleep Apnea Syndromes , Bone Diseases, Metabolic/chemically induced , Bone Diseases, Metabolic/drug therapy , Caffeine/adverse effects , Cohort Studies , Female , Humans , Infant, Newborn , Infant, Premature , Infant, Very Low Birth Weight , Male , Retrospective Studies , Vitamins
12.
Photodermatol Photoimmunol Photomed ; 38(5): 495-500, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35108414

ABSTRACT

BACKGROUND: Melasma is an acquired state of hyperpigmentation that most commonly affects the face. The use of sunscreen is essential in melasma treatment. We sought to investigate patients' perspectives and behaviors toward sunscreen usage. METHODS: A cross-sectional hospital-based study targeted 418 melasma patients from May 2019 to May 2021. Data regarding socio-demographic characteristics and the knowledge, attitude, and behavior toward sunscreen and sun exposure were collected and analyzed. Furthermore, a complete clinical assessment was done. RESULTS: The mean age of the patients was 35.4 ± 8.6 years. Melasma distribution was mostly centro-facial (49.8%). The mean duration of the disease was 22.3 ± 11.6 months, with a mean Melasma Area and Severity Index (MASI) score of 18.6 ± 8.9. Only 170 patients believed that sun exposure played a role in their disease. Skin darkening was the most recognized effect of sun exposure by 92.9% of participants. 58.6% reported using sunscreen with a higher female predominance (p < .001), while males reported more broad-spectrum sunscreen usage (p < .001). The reason that was reported the most behind not using sunscreen was the high cost (94%). CONCLUSIONS: Our study showed a sound level of knowledge regarding the effects of sun exposure, and sunscreen advantages and disadvantages, with relatively inadequate translation into their attitudes and practices regarding sun-protective behaviors. The use of sunscreen among the patients was average in numbers with a higher female predominance.


Subject(s)
Hyperpigmentation , Melanosis , Adult , Cross-Sectional Studies , Female , Humans , Hyperpigmentation/drug therapy , Male , Melanosis/drug therapy , Melanosis/prevention & control , Perception , Sunscreening Agents/therapeutic use
13.
Nat Rev Urol ; 19(2): 101-115, 2022 02.
Article in English | MEDLINE | ID: mdl-34667303

ABSTRACT

Localized prostate cancer shows great clinical, genetic and environmental heterogeneity; however, prostate cancer treatment is currently guided solely by clinical staging, serum PSA levels and histology. Increasingly, the roles of differential genomics, multifocality and spatial distribution in tumorigenesis are being considered to further personalize treatment. The human prostate is divided into three zones based on its histological features: the peripheral zone (PZ), the transition zone (TZ) and the central zone (CZ). Each zone has variable prostate cancer incidence, prognosis and outcomes, with TZ prostate tumours having better clinical outcomes than PZ and CZ tumours. Molecular and cell biological studies can improve understanding of the unique molecular, genomic and zonal cell type features that underlie the differences in tumour progression and aggression between the zones. The unique biology of each zonal tumour type could help to guide individualized treatment and patient risk stratification.


Subject(s)
Prostate/pathology , Prostatic Neoplasms/pathology , Biomarkers, Tumor/blood , Humans , Male , Organ Size , Prognosis , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood
14.
PLoS One ; 16(10): e0230164, 2021.
Article in English | MEDLINE | ID: mdl-34613963

ABSTRACT

With the advent of high-throughput technologies, life sciences are generating a huge amount of varied biomolecular data. Global gene expression profiles provide a snapshot of all the genes that are transcribed in a cell or in a tissue under a particular condition. The high-dimensionality of such gene expression data (i.e., very large number of features/genes analyzed with relatively much less number of samples) makes it difficult to identify the key genes (biomarkers) that are truly attributing to a particular phenotype or condition, (such as cancer), de novo. For identifying the key genes from gene expression data, among the existing literature, mutual information (MI) is one of the most successful criteria. However, the correction of MI for finite sample is not taken into account in this regard. It is also important to incorporate dynamic discretization of genes for more relevant gene selection, although this is not considered in the available methods. Besides, it is usually suggested in current studies to remove redundant genes which is particularly inappropriate for biological data, as a group of genes may connect to each other for downstreaming proteins. Thus, despite being redundant, it is needed to add the genes which provide additional useful information for the disease. Addressing these issues, we proposed Mutual information based Gene Selection method (MGS) for selecting informative genes. Moreover, to rank these selected genes, we extended MGS and propose two ranking methods on the selected genes, such as MGSf-based on frequency and MGSrf-based on Random Forest. The proposed method not only obtained better classification rates on gene expression datasets derived from different gene expression studies compared to recently reported methods but also detected the key genes relevant to pathways with a causal relationship to the disease, which indicate that it will also able to find the responsible genes for an unknown disease data.


Subject(s)
Gene Expression Profiling/methods , Gene Expression/genetics , High-Throughput Screening Assays/methods , Algorithms , Humans , Phenotype
15.
PLoS One ; 16(2): e0247472, 2021.
Article in English | MEDLINE | ID: mdl-33606840

ABSTRACT

BACKGROUND: Bone morphogenetic proteins (BMP) are multifunctional proteins. They work as cytokines regulating osteogenesis during fracture healing process. The objectives of this study were to assess changes in BMPs during fracture and their correlations to Fracture's healing. METHODS: Case-Control hospital-based study conducted from January 2018 to January 2019. Demographic data, anthropometric measurements, and blood samples were collected from patients and controls (18-65 years old). Plasma concentrations of selected BMPs and vitamin D were measured using quantitative enzyme linked immunosorbent assay (ELISA). SPSS version 25 was used to calculate frequencies, Pearson correlation tests, chi-square and unpaired t-test. RESULTS: Sixty-five patients with fractures and Sixty-five controls were studied. Means of plasma concentrations were (TGFß1 = 21.07 ng/ml ±8.49 and 19.8 ng/ml ±7.2) (BMP-2 = 76.3 pg/ml ± 156.6 and 55.5 ng/ml ± 127.9) (BMP-7 = 13.02 pg/ml ±43.5 and 64.6pg/ml ±250) (BMP-10 = 8.14 pg/ml ±12.7 and 5.48 pg/ml ±11.3) (Vitamin D mean was 24.94 ng/ml ±13.2 and 26.2 ng/ml ±11.6) in patients and controls, respectively. Forty-five subjects were enrolled into follow up study: 30 males, 15 females. Healing time mean was 4.13± 2.6 months. No significant correlation between BMP-2/BMP-7 with healing time. CONCLUSIONS: BMP-7 was significantly lowers in the plasma of patients that controls (P = 0.042). Low Vitamin D was observed among Sudanese participants.


Subject(s)
Bone Morphogenetic Protein 2/blood , Bone Morphogenetic Protein 7/blood , Bone Morphogenetic Proteins/blood , Fractures, Bone/blood , Transforming Growth Factor beta1/blood , Vitamin D/blood , Adolescent , Adult , Aged , Case-Control Studies , Female , Fracture Healing/physiology , Humans , Male , Middle Aged , Sudan , Young Adult
17.
Nat Genet ; 53(1): 65-75, 2021 01.
Article in English | MEDLINE | ID: mdl-33398198

ABSTRACT

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.


Subject(s)
Genetic Loci , Genetic Predisposition to Disease , Genome-Wide Association Study , Prostatic Neoplasms/genetics , Racial Groups/genetics , Humans , Male , Middle Aged , Molecular Sequence Annotation , Neoplasm Invasiveness , Odds Ratio , Prostatic Neoplasms/diagnosis , Risk Factors
18.
Int J Hematol Oncol Stem Cell Res ; 15(3): 139-144, 2021 Jul 01.
Article in English | MEDLINE | ID: mdl-35082994

ABSTRACT

Background: Immune thrombocytopenic purpura (ITP) defined as a bleeding disorder in which the number and production of platelets reduced by the immune system; however, the destruction of peripheral blood platelets also occurs. Although its exact etiology and pathogenesis not already know, several studies have shown that Epstein-Barr virus (EBV) and cytomegalovirus (CMV) known as possible causative agents of ITP. This investigation aims to evaluate the presence of CMV and EBV in two groups of case and control by polymerase chain reaction (PCR). Materials and Methods: we considered the presence of CMV and EBV in 48 acute ITP patients and 48 healthy people. Study participants were recruited from Ahvaz Shafa Hospital between 2017 and 2018 and the presence of two viruses was investigated by (PCR). Results: Out of 48 acute ITP patients, the CMV DNA was detected from the blood of 12 (25%) patients and the EBV DNA from the blood of 2 (4.2%) other patients. In addition, only one patient was (2.1%) co-infected with CMV and EBV. In contrast, in 48 healthy subjects, 3 (6.6%) had CMV and none of the control group was infected with EBV. Conclusion: Due to the presence of both EBV and CMV in the acute ITP patients in Ahvaz, they can be considered as factors in the progression of this disease. Therefore, consideration of the methods of elimination and treatment of these two viruses in these patients may be used as a treatment strategy in ITP patients in the future.

19.
Cureus ; 13(12): e20427, 2021 Dec.
Article in English | MEDLINE | ID: mdl-35047264

ABSTRACT

Introduction The concept of illness severity scoring has been around for long and is currently being utilized in many neonatal intensive care unit (NICU). Scoring systems that help to quantify mortality risks on the basis of clinical conditions not only help in estimating prognosis, but also help clinicians in making decisions particularly in situations presenting with dilemmas. This study aims to determine SNAPPE-II (Score for Neonatal Acute Physiology-Perinatal Extension) score as a predictor of neonatal mortality in NICU at a tertiary care hospital in Pakistan. Methodology It was a longitudinal cohort study. The study was conducted at a neonatal intensive care unit (NICU) of Aga Khan University Hospital (AKUH) Karachi, Pakistan. All neonates were included who were born in AKUH and who needed respiratory support in NICU. Results A total of 333 newborns were enrolled for this study. Out of those 30 (9.1%) neonates expired while 298 (90.9%) survived. Area Under the Receiver operative curve was calculated to obtain the SNAPPE-II score's diagnostic discrimination ability. Area under the curve (AUC) was 80.2±4.6% which corresponds to a moderate diagnostic accuracy for the prediction of neonatal mortality. The 95% CI for this was between 71.1-89.2%. SNAPPE-II category III (>40) was found to be the strongest predictor of mortality, with a sensitivity of 40% and a specificity of 98.7%. Conclusion The SNAPPE-II scoring system, we conclude, might be a valuable technique for predicting newborn death in resource-constrained NICUs.

20.
Osteoporos Sarcopenia ; 6(2): 53-58, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32715094

ABSTRACT

OBJECTIVES: The accuracy of FRAX® as a screening tool to identify osteoporosis and how it compares with tools such as Osteoporosis Self-Assessment Tool for Asians (OSTA), in Southeast Asian women has so far been unexplored. We aimed to determine the FRAX® thresholds that accurately identify densitometric osteoporosis and to compare its performance with that of OSTA for this purpose. METHODS: Singaporean postmenopausal women (n = 1056) were evaluated. FRAX® Major Osteoporotic Fracture Probability (MOFP), Hip Fracture Probability (HFP) scores, and OSTA indices were calculated. Receiver operating characteristic (ROC) curves were constructed and via the Youden index, the optimal cut-off points of balanced sensitivity and specificity for dual energy X-ray absorptiometry (DXA)-defined osteoporosis were identified and the performance characteristics were compared. RESULTS: A FRAX® MOFP threshold of ≥3.7% had sensitivity, specificity, positive predictive value and negative predictive value of 0.78 (0.73-0.83), 0.63 (0.59-0.66), 0.4 (0.36-0.44), and 0.9 (0.87-0.92), respectively in identifying osteoporosis. The corresponding values for a HFP threshold of ≥0.6% were 0.85 (0.80-0.89), 0.58 (0.55-0.62), 0.39 (0.35-0.43), and 0.92 (0.9-0.94) and that for an OSTA index cut-off of ≤ -1.2 were 0.76 (0.70-0.81), 0.74 (0.71-0.77), 0.48 (0.43-0.54), and 0.91 (0.88-0.93). The area under the ROC curves were 82.8% (79.9%-85.6%), 77.6% (74.2%-81%), and 79.6% (76.5%-82.8%) for OSTA, MOFP, and HFP thresholds respectively. CONCLUSIONS: FRAX® and OSTA perform comparably in identifying osteoporosis in our population. OSTA has only 2 parameters and may be simpler to use. However, FRAX® may also have a role in primary screening to identify the postmenopausal woman to be referred for DXA scanning and may help facilitate fracture risk reduction discussions with the patient.

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