UTILITY OF ALBUMIN CREATININE RATIO (ACR) IN MONITORING DIABETIC RETINOPATHY AND NEPHROPATHY

Objective: To evaluate Albumin Creatinine Ratio (ACR) as a screening marker for detection of early diabetic retinopathy in parallel with diabetic nephropathy. Study Design: Comparative cross sectional study. Place and Duration of Study: Department of Ophthalmology and Chemical Pathology & Endocrinology, Combined Military Hospital, Multan, from Jul 2017 to Jul 2019. Methodology: A total of 386 diagnosed patients of type II diabetes mellitus who reported for follow up and monitoring in Combined Military Hospital Multan, underwent initial screening with urine dip strip, if protein positive patients were excluded if negative patients were included in the study. Urinary albumin creatinine ratio was calculated as mg/mmol of creatinine. For staging of diabetic retinopathy; participants underwent ocular examinations. Pearson correlation was performed and ROC was constructed at different cut-offs. Results: Out of the 386 (100%) patients with type II diabetes 284 (74%) had albumin creatinine ratio <3 mg/mmol and 102 (26%) had micro albuminuria i.e. albumin creatinine ratio 3-30 mg/mmol. Among normal albumin uric cases (284) only 52 (18%) patients had mild to moderate non-proliferative diabetic retinopathy. Conclusion: Albumin creatinine ratio is associated with severity of diabetic retinopathy. Since diabetic retinopathy stages have been identified in normal albumin uric range, there is need to determine a definite cut off value (<3 mg/mmol) of ACR for using it as a screening marker for diabetic retinopathy.

The Reticulocyte Hemoglobin Equivalent as a Screening Marker for Iron Deficiency and Iron Deficiency Anemia in Children

Background: Iron deficiency (ID) is one of the most common nutritional deficiencies in children worldwide and may result in iron deficiency anemia (IDA). The reticulocyte hemoglobin equivalent (Ret-He) provides information about the current availability of iron in erythropoiesis. This study aims to examine the validation of Ret-He as a screening marker for ID and IDA in children. Methods: Blood samples were retrospectively obtained from medical records. Anemia was defined according to the definition provided by the World Health Organization (WHO) for children. ID was defined by transferrin saturation (TSAT) < 20% and ferritin < 100 ng/mL. Children were classified into four groups: IDA, non-anemia iron deficiency (NAID), control and others. Results: Out of 970 children, 332 (34.2%) had NAID and 278 (28.7%) presented with IDA. Analysis revealed that Ret-He significantly correlates with ferritin (rho = 0.41; p < 0.001), TSAT (rho = 0.66; p < 0.001) and soluble transferrin receptor (sTfR) (rho = −0.72; p < 0.001). For ROC analysis, the area under the curve (AUC) was 0.771 for Ret-He detecting ID and 0.845 for detecting IDA. The cut-off value for Ret-He to diagnose ID was 33.5 pg (sensitivity 90.7%; specificity 35.8%) and 31.6 pg (sensitivity 90.6%; specificity 50.4%) to diagnose IDA. Conclusions: The present study demonstrates Ret-He to be a screening marker for ID and IDA in children. Furthermore, Ret-He can be used as a single screening parameter for ID and IDA in children without considering other iron parameters. Economically, the use of Ret-He is highly relevant, as it can save one blood tube per patient and additional costs.

Plasma Globotriaosylsphingosine and α-Galactosidase A Activity as a Combined Screening Biomarker for Fabry Disease in a Large Japanese Cohort

Fabry disease is an X-linked disorder of α-galactosidase A (GLA) deficiency. Our previous interim analysis (1 July 2014 to 31 December 2015) revealed plasma globotriaosylsphingosine as a promising primary screening biomarker for Fabry disease probands. Herein, we report the final results, including patients enrolled from 1 January to 31 December 2016 for evaluating the potential of plasma globotriaosylsphingosine and GLA activity as a combined screening marker. We screened 5691 patients (3439 males) referred from 237 Japanese specialty clinics based on clinical findings suggestive of Fabry disease using plasma globotriaosylsphingosine and GLA activity as primary screening markers, and GLA variant status as a secondary screening marker. Of the 14 males who tested positive in the globotriaosylsphingosine screen (≥2.0 ng/mL), 11 with low GLA activity (<4.0 nmol/h/mL) displayed GLA variants (four classic, seven late-onset) and one with normal GLA activity and no pathogenic variant displayed lamellar bodies in affected organs, indicating late-onset biopsy-proven Fabry disease. Of the 19 females who tested positive in the globotriaosylsphingosine screen, eight with low GLA activity displayed GLA variants (six classic, two late-onset) and five with normal GLA activity displayed a GLA variant (one classic) and no pathogenic variant (four late-onset biopsy-proven). The combination of plasma globotriaosylsphingosine and GLA activity can be a primary screening biomarker for classic, late-onset, and late-onset biopsy-proven Fabry disease probands.

C4OH is a potential newborn screening marker—a multicenter retrospective study of patients with beta-ketothiolase deficiency in China

Background Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disorder caused by biallelic mutation of ACAT1 that affects both isoleucine catabolism and ketolysis. There is little information available regarding the incidence, newborn screening (NBS), and mutational spectrum of BKTD in China. Results We collected NBS, biochemical, clinical, and ACAT1 mutation data from 18 provinces or municipalities in China between January 2009 and May 2020, and systematically assessed all available published data from Chinese BKTD patients. A total of 16,088,190 newborns were screened and 14 patients were identified through NBS, with an estimated incidence of 1 per 1 million newborns in China. In total, twenty-nine patients were genetically diagnosed with BKTD, 12 of which were newly identified. Most patients exhibited typical blood acylcarnitine and urinary organic acid profiles. Interestingly, almost all patients (15/16, 94%) showed elevated 3-hydroxybutyrylcarnitine (C4OH) levels. Eighteen patients presented with acute metabolic decompensations and displayed variable clinical symptoms. The acute episodes of nine patients were triggered by infections, diarrhea, or an inflammatory response to vaccination. Approximately two-thirds of patients had favorable outcomes, one showed a developmental delay and three died. Twenty-seven distinct variants were identified in ACAT1, among which five were found to be novel. Conclusion This study presented the largest series of BKTD cohorts in China. Our results indicated that C4OH is a useful marker for the detection of BKTD. The performance of BKTD NBS could be improved by the addition of C4OH to the current panel of 3-hydroxyisovalerylcarnitine and tiglylcarnitine markers in NBS. The mutational spectrum and molecular profiles of ACAT1 in the Chinese population were expanded with five newly identified variants.

Kanamycin in Cereal Biotechnology: A Screening or a Selectable Marker?

Kanamycin is a widely used selection agent in dicot-plant genetic transformation systems. In monocots, however, it does not seem to be effective as it has no or minimal effect on the normal growth of non-transformed plants. Kanamycin was previously demonstrated to bleach the pigments of the non-transgenic plants. This may yield the idea that kanamycin can be used as an effective screening marker rather than a selectable marker in monocots. Copyright (c) 2021 Malik Nawaz Shuja, Hasan Riaz, Muhsin Jamal, Muhammad Imran

Kanamycin in Cereal Biotechnology: A Screening or a Selectable Marker?

Kanamycin is a widely used selection agent in dicot-plant genetic transformation systems. In monocots, however, it does not seem to be effective as it has no or minimal effect on the normal growth of non-transformed plants. Kanamycin was previously demonstrated to bleach the pigments of the non-transgenic plants. This may yield the idea that kanamycin can be used as an effective screening marker rather than a selectable marker in monocots.

Kanamycin in Cereal Biotechnology: A Screening or a Selectable Marker?

Kanamycin is a widely used selection agent in dicot-plant genetic transformation systems. In monocots, however, it does not seem to be effective as it has no or minimal effect on the normal growth of non-transformed plants. Kanamycin was previously demonstrated to bleach the pigments of the non-transgenic plants. This may yield the idea that kanamycin can be used as an effective screening marker rather than a selectable marker in monocots.

Kanamycin in Cereal Biotechnology: A Screening or a Selectable Marker?

Kanamycin is a widely used selection agent in dicot-plant genetic transformation systems. In monocots, however, it does not seem to be effective as it has no or minimal effect on the normal growth of non-transformed plants. Kanamycin was previously demonstrated to bleach the pigments of the non-transgenic plants. This may yield the idea that kanamycin can be used as an effective screening marker rather than a selectable marker in monocots.