Continuous Glucose Monitoring for Prediabetes: What Are the Best Metrics?

BACKGROUND: Continuous glucose monitoring (CGM) has transformed the care of type 1 and type 2 diabetes, and there is potential for CGM to also become influential in prediabetes identification and management. However, to date, we do not have any consensus guidelines or high-quality evidence to guide CGM goals and metrics for use in prediabetes. METHODS: We searched PubMed for all English-language articles on CGM use in nonpregnant adults with prediabetes published by November 1, 2023. We excluded any articles that included subjects with type 1 diabetes or who were known to be at risk for type 1 diabetes due to positive islet autoantibodies. RESULTS: Based on the limited data available, we suggest possible CGM metrics to be used for individuals with prediabetes. We also explore the role that glycemic variability (GV) plays in the transition from normoglycemia to prediabetes. CONCLUSIONS: Glycemic variability indices beyond the standard deviation and coefficient of variation are emerging as prominent identifiers of early dysglycemia. One GV index in particular, the mean amplitude of glycemic excursion (MAGE), may play a key future role in CGM metrics for prediabetes and is highlighted in this review.

Genetic variation of CYP2C9 gene and its correlation with cardiovascular disease risk factors.

BACKGROUND: The major enzyme that is responsible for Sulfonylureas (SUs) metabolism is hepatic cytochrome P-450 2C9 (CYP2C9). It is encoded by the polymorphic gene CYP2C9, which has many allelic variants, among those the CYP2C9*2 and CYP2C9*3 are the most common and clinically significant allelic variations. People with diabetes mellitus type 2 (T2DM) are more likely to develop cardiovascular disease (CVD), and their risk of dying from it is more than two times higher than that of people without the condition. The purpose of this study was to evaluate the association of genetic variations in the CYP2C9 gene with cardiovascular risk factors by investigating CYP2C9*1, *2, *3, *5, *11, and *13 allelic variants. METHODS AND RESULTS: A total of 226 participants were enrolled in the current case-control study. Allele-specific amplification- PCR (ASA-PCR) was used to determine the allele of different variations and the results were confirmed by sequencing. The findings of this study showed the presence of the CYP2C9*2 allele in the T2DM group does not differ from its percentage in the control group. Also, CYP2C9*3 allele frequencies identified by Hardy-Weinberg equilibrium (HWE) analysis law were not significant, p = 0.6593 and 0.5828 in T2DM and control groups. There is no statistically significant difference between the control and diabetes groups involving the distribution of CYP2C9 alleles and CYP2C9*5, *11, and *13 polymorphisms were absent in the Iraqi population. No carrier for the CYP2C9*3 homozygous state was found in both groups. CONCLUSIONS: According to these results T2DM patients with the CYP2C9*2 and *3 variants have an increased risk of developing hypertension.

The Association between the Number of Vacuum Pop-Offs and Adverse Neonatal Outcomes.

OBJECTIVE: Obstetrical vacuum manufacturers have long recommended a maximum of two to three pop-offs be allowed before abandoning the procedure. However, there is a paucity of evidence on the safety of vacuum-assisted vaginal delivery in relation to the number of pop-offs to support this recommendation. Our objective was to examine whether the number of pop-offs in a vacuum-assisted vaginal delivery was associated with adverse neonatal outcomes. STUDY DESIGN: This is a retrospective cohort study of women who underwent a trial of a vacuum-assisted vaginal delivery at a single tertiary care institution between October 2005 and June 2014. Maternal and fetal factors associated with the number of pop-offs were examined in bivariable analyses. Multivariable analyses were performed to determine the independent association of the number of pop-offs with adverse neonatal outcomes. RESULTS: Of the 1,730 women who met inclusion criteria, 1,293 (74.7%) had no pop-offs, 240 (13.9%) had one pop-off, 128 (7.4%) had two pop-offs, and 69 (4.0%) had three or more pop-offs. Neonatal scalp/facial lacerations, intracranial hemorrhage, seizures, central nervous system depression, and neonatal intensive care unit admission were all associated with the number of pop-offs in bivariable analyses. In multivariable analyses, compared to no pop-offs, having any vacuum pop-offs was associated with an increased odds of adverse neonatal outcomes. However, there was not a consistent dose-response relationship. CONCLUSION: While having vacuum pop-offs in a vacuum-assisted vaginal delivery was associated with an increased risk of adverse neonatal outcomes, there did not appear to be a dose-dependent association with the number of pop-offs. KEY POINTS: · There are no specific guidelines on how many pop-offs can be allowed before abandoning a vacuum-assisted vaginal delivery.. · Having any vacuum pop-offs was associated with an increased risk of adverse neonatal outcomes.. · There was no dose-dependent association between number of pop-offs and adverse neonatal outcomes..

Genetic analysis of X-chromosomal short tandem repeat (X-STR) frequencies in Arab Iraqi male population.

BACKGROUND: The X-chromosome short tandem repeat (STR) polymorphisms are a particular tool in the fields of human population genetics and personal identification. It was necessary in investigating complex kinship or deficiency cases in conditions where information on mitochondrial DNA (mtDNA) or Y chromosome polymorphisms have been used to explore their direct paternal line. This study aimed to investigate the allele frequency of (12X-STR) of 200 unrelated males from different region of Baghdad City to serve as a reference data base for individual identification in Iraqi population. RESULTS: Twelve X-STR loci (DXS7424, HPRTB, DXS8377, GATA31E08, DXS7423, DXS8378, DXS9895, DXS10074, DXS6809, DXS7133, DXS101, DXS6807) were successfully amplified by multiplex PCR and divided into four groups. According to measures of allele frequency, the higher alleles frequency were 16, 11, 46, 11, 14, 10, 15, 15.2, 35, 11, 25, and 11 while the lowest alleles frequency were 11, 9, 52,53, 7, 17, 14, 13, 12.2,17, 36, 15, 16, 22, 29, and 17 that observed at the 12 loci respectively. Forensic efficiency parameter for DXS8377 locus in the first group showed highest polymorphic allele in the Iraqi Arab population with the frequencies ranging from 0.005 to 0.16%. The power of discrimination (PD) value ranged from 0.663 for DXS7423 locus and 0.9066 for DXS8377 locus. In addition, the polymorphism information content (PIC) value ranged from 0.602974 for DXS7423 locus to 0.899206 for DXS8377 locus. CONCLUSIONS: Overall the X-STR markers become used as an important source of information beside the autosomal and Y-STR markers, especially for kinship testing and haplotype analysis.

ApoB gene polymorphism (rs676210) and its pharmacogenetics impact on atorvastatin response among Iraqi population with coronary artery disease.

BACKGROUND: Drug response is below genetic influence, proven by the genetic variants. Pharmacogenetics trials are performed in many diseases, including coronary artery disease. This study was designed to determine the genetic polymorphism (rs676210) Pro2739leu G > A in the lipid metabolism-related gene (ApoB gene) and its pharmacogenetic role in the response to atorvastatin drug in a sample of Iraqi population with coronary artery disease (CAD). RESULTS: Significant differences of genotype distribution in CAD patients and controls were observed in ApoB+ 8216 in Iraqi population from Hardy Weinberg Analysis. It also found that dramatic difference of low-density lipoprotein (LDL-C) level in response to 40 mg/day of atorvastatin therapy, the minor allele (A) observed a greater LDL-C lowering than the wild type allele (G). In ANOVA analysis, the result showed that the rs676210, Pro2739Leu, in ApoB gene increased non significantly, but gradually in plasma level of total cholesterol (TC), triglyceride (TG), very low-density lipoprotein (VLDL), and oxidize low-density lipoprotein (oxLDL) in the order of genotype AA, GA, and GG in response to 40 mg atorvastatin. CONCLUSION: We found the results highlighted the function of the rs676210, Pro2739Leu, in the ApoB gene in CAD etiology, and the findings support this variant's impact in predicting the response of (LDL-C) to 40 mg of atorvastatin therapy. ApoB gene polymorphism (rs676210, Pro2739Leu), specifically the AA genotype, may help to identify individuals who will profit from atorvastatin's lowering effects.

Nasopharyngeal Salivary Gland Anlage Tumour: A rare cause of neonatal respiratory distress.

A salivary gland anlage tumour (SGAT) is a very rare type of benign tumour that usually presents in early infancy with respiratory distress which is exacerbated upon feeding. We report a full-term male neonate who was referred to the Al Nahdha Hospital, Muscat, Oman, in 2015 with severe neonatal respiratory distress due to a nasopharyngeal obstruction immediately after birth. Computed tomography and magnetic resonance imaging revealed a well-circumscribed mass in the nasopharynx, without intracranial extension. Histopathological analysis of the lesion confirmed a diagnosis of SGAT. Following excision of the tumour, the postoperative period was uneventful. No recurrence was observed over the next two years. This case report highlights the importance of the early recognition of this extremely rare and potentially life-threatening, yet easily curable, condition.

Detection of Metallo-ß-Lactamase Producing Pseudomonas aeruginosa Isolated from Public and Private Hospitals in Baghdad, Iraq.

Metallo-ß-lactamase (MBL) producing Pseudomonas aeruginosa has been reported to be an important nosocomial infection. Its intrinsic and acquired resistance to various antimicrobial agents and its ability to develop multidrug resistance imposes a serious therapeutic problem. Different clinical samples were collected from public and private hospitals in Baghdad city, Iraq. Bacterial identification was done using conventional cultural, biochemical tests, and VITEk 2 system. Minimum inhibitory concentration (MIC) testing was performed using VITEK 2 automated system. Each P. aeruginosa isolates showed resistance to Carbapenems (Imipenem and Meropenem) were subjected to Imipenem-EDTA combined disc synergy test (CDST) to investigate the production of MBL (confirmative test). The presence of bla-genes encoded IMP, VIM, and SPM-1 was detected by conventional PCR technique. A total of 75 P. aeruginosa isolates were isolated, 16 (21.3%) were able to grow on MacConkey agar supplemented with Meropenem 4mg/L (MMAC). The MIC of different antibiotics showed that 6 (37.5 %) isolates were Carbapenem resistant, MIC ≥16 µg/ml while 4 (25%) isolates appear to be MBL producer using CDST test. PCR assay revealed that 3 (50%), 1 (16.6%) of the carbapenem resistant isolates harbored blaIMP, blaSPM-1 genes, respectively. blaVIM gene was not detected in this study. The prevalence of multi-drug resistant P. aeruginosa isolates especially Carbapenem resistant bacteria was increased in Baghdad province. The blaIMP was the predominant among the MBLs genes in P. aeruginosa in this study.

Antitumor activity of bacteriophages in murine experimental cancer models caused possibly by inhibition of beta3 integrin signaling pathway.

Bacteriophages (phages) as bacterial viruses are generally believed to have no intrinsic tropism for mammalian cells. In this study the interactions between phages and various eukaryotic cells were investigated. Binding of phages to the membranes of cancer and normal blood cells was observed. Moreover, it was shown that the wild-type phage T4 (wtT4) and its substrain HAP1 with enhanced affinity for melanoma cells inhibit markedly and significantly experimental lung metastasis of murine B16 melanoma cells by 47% and 80%, respectively. A possible molecular mechanism of these effects, namely a specific interaction between the Lys-Gly-Asp motif of the phage protein 24 and beta3-integrin receptors on target cells is proposed. It was also shown that anti-beta3 antibodies and synthetic peptides mimicking natural beta3 ligands inhibit the phage binding to cancer cells. This is in line with the well-described beta3 integrin-dependent mechanism of tumor metastasis. It is concluded that the blocking of beta3 integrins by phage preparations results in a significant decrease in tumor invasiveness.

CEA-related proteins on human urothelial cell lines of different transformation grades.

CEA family proteins from human urothelial cell lines of different transformation grades were characterized by flow cytometry and Western blotting using monoclonal antibodies: 26/3/13, D14HD11, 9A6 and 4/3/17. The following observations were made: (i) the urothelial cell lines, representing transformation grade III (TGr III, tumorigenic, invasive cells), were characterized by the presence of a component with molecular mass 110-135 kDa, most probably representing biliary glycoprotein (BGP); (ii) BGP was absent in non-tumorigenic and non-invasive TGr II urothelial cell lines; (iii) a protein band with apparent molecular mass 180 kDa, and migrating as a CEA standard was detected in only one of seven urothelial cell lines analyzed; (iv) a broad band of apparent molecular mass migrating at 65-90 kDa, probably representing NCA-50/90, was found in two tumorigenic and invasive cell lines, HCV 29T and Hu 1703He.

Cytotoxicity and proliferation of splenocytes and lymph node cells from adjuvant-treated nude mice. Studies of natural and in vitro activation.

The cytotoxicity of NK cells and lymphocytes derived from nonadherent splenocytes (SPL) and regional lymph node cells (LNC) from complete Freund's adjuvant (CFA)-treated athymic nude young (4-6 weeks) and aged (over 1 year) BALB/c nu/nu mice in vitro activated with rIL-2, anti-CD3 mAb or PPD was analyzed and compared to SPL and LNC from age-matched euthymic BALB/c mice. The high natural cytotoxicity to YAC-1 target cells of SPL or LNC could be augmented by 48 h stimulation in vitro with rIL-2, especially when derived from young nude BALB/c mice. The increase in cytotoxic activity was accompanied by increased proliferative activity of both SPL and LNC, which showed statistically significant differences between the rates of stimulation of cells from the young and aged groups. Anti-CD3 mAb strongly activated the cytotoxicity of BALB/c euthymic donor effector cells against P-815 target cells, corresponding to a very high proliferative activity of these cells, but anti-CD3 mAb did not lead to activation of effector cells from nude donors. FACS analyses of antigenic markers similarly showed an increased number of T cells in LNC from aged BALB/c nude donors, which, however, never reached the levels of those of euthymic animals.

Growth inhibition of transplantable tumors in mice by mIL-2-secreting murine plasmocytoma cells used alone or in combination with a cytostatic agent.

The non-tumorigenic cells of X63-Ag8.653 mouse plasmocytoma line transfected with murine interleukin 2 cDNA (X63-mIL-2) served us as the source of the cytokine to induce or to augment antitumor response in syngeneic BALB/c or semisyngeneic (CD2F1) mice challenged subcutaneously with either "wild" line tumor cells (X63/0) or with non-related methylcholantrene induced BFS1 fibrosarcoma of BALB/c mice. When applied peritumorally in several injections (2 to 6) to mice with non-advanced stages of the tumors, IL-2-secreting cells were able to cause tumor growth retardation in most of the treated mice and to induce tumor rejection in some of them. The combination chemoimmunotherapy was attempted in mice with advanced BFS1 fibrosarcoma using compound CBM-4A (the bromoanalog of ifosfamide) administered at various time (4 h or 3, 5 or 7 days) before the first of two local injections of transfected cells. The strategy proved to be more efficient in the tumor growth inhibition as compared with the cytostatic alone.

Effect of peritoneal cells on tumors cells growth in vitro.

The cytotoxic and cytostatic activity of PMA-treated macrophages, obtained from pristane-primed BALB/c mice, was analyzed in vitro. The activated macrophages were cytotoxic and cytostatic for YAC-1 lymphoma, P-388 leukemia and P-815 mastocytoma target cells. However, the RPC-5 plasmacytoma target cells appeared to be resistant to their cytotoxicity. The observed cytotoxic or cytostatic effects of macrophages in vitro were not correlated with their ability to produce the superoxide ion. Cytotoxic activity of NK cells, obtained from pristane-primed mice, was also studied. No differences in cytotoxicity of NK cells obtained from pristane-treated and untreated donors, were found. However, only the effector cells from untreated mice were able to respond to stimulatory effect of polyinosinic acid-polycytidylic acid-poly-L-lysine (poly ICLC).

The effect of adherent peritoneal exudate cells (APECs) and their products on the RPC-5 plasmacytoma growth in vitro.

The ability of peritoneal exudate cells (PECs) and their adherent (APECs) and nonadherent (NAPECs) fractions to enhance RPC-5 plasmacytoma growth in vitro was studied. The capability of these cells to bind RPC-5 cells and influence of the binding on cytolysis tumor cells by activated with C. parvum macrophages was also determined. The effector cells were harvested from mice injected i.p. with pristane, thioglicollate medium or C. parvum or from intact mice. The effect of supernatants from the in vitro cultured PECs, APECs or NAPECs on growth RPC-5 cells were also tested. It was found that the RPC-5 plasmacytoma growth was enhanced only by cells obtained from mice treated with pristane, or by supernatants from cultured PECs and APECs derived from pristane treated mice. The adherent cells from pristane treated mice were able to bind tumor cells. The tumor cells preexposed to adherent cells from pristane stimulated mice were resistant to lysis by activated with C. parvum macrophages.

The effect of adherent peritoneal exudate cells on plasmacytoma growth in BALB/c mice.

The effect of adherent peritoneal exudate cells (APECs) from pristane treated and intact mice was studied by Winn's test. The experiments were performed with the use of plasmacytoma cell lines TEPC-15f, MP-26 and five primary lines. The studies showed that APECs from mice exposed to treatment with pristane were able to stimulate growth of both TEPC-15f and MP-26 plasmacytoma. The primary plasmacytoma lines adapted to intraperitoneal growth more easily in the presence of adherent cells than when they were given alone.

Specific killing of mouse leukemic cells with ricin A-chain immunotoxin.

Monoclonal IgM antibody against L1210V leukemia was coupled with ricin A-chain using N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) as a cross--linking agent. The coniugate had potent concentration--dependent cytotoxicity against L1210V, L1210 and RL male 1 cells being completely non toxic to EL-4, P388, RPC-5 and mouse bone marrow cells. The minimum time required for killing L120V leukemia cells was 30h of in vitro exposure, at a concentration 10(-6) M (as assessed by trypan blue test). However, 1h contact of L1210V cells with immunotoxin was sufficient to completely inhibit proliferation of leukemic cells subsequently inoculated into compatible mice. The toxicity could be potentiated by addition of NH4Cl, that shortened minimum exposure time to 18h and 45 min respectively.

Identification of plasminogen activator releasing activity in the neurohypophysis.

Vasopressin (AVP) and some of its synthetic analogues, for example 1 desamino 8-D-AVP (DDAVP), induce plasminogen activator (PA) release in vivo. It has been proposed that this occurs via the release from the central nervous system of a plasminogen activator releasing hormone (PARH). The present study shows that a crude extract of bovine posterior pituitary, but not of the anterior pituitary or of the hypothalamus, induces a marked increase of circulating PA in anaesthetized rats. PA release appears to be caused by AVP because no other PA releasing activities could be identified in or isolated from the extract. In addition, no PA-releasing activity was found in extracts of pituitary glands of rats congenitally deficient in vasopressin. The following experiments did not reveal central nervous system involvement in the PA-release caused by AVP or DDAVP. Perfusion of isolated organs (rat heart and rat liver) with AVP resulted in PA-release. In squirrel monkeys, comparable PA levels were found in the venous return following intrafemoral or intracarotid injection of AVP. Moreover, when plasma obtained 2 min following AVP or DDAVP injection was transfused to a receiving animal no PA release was observed. Thus our present findings do not support the hypothesis that the fibrinolytic response to AVP is mediated by the release of a specific peptide hormone from the central nervous system.

Biological properties of human tissue-type plasminogen activator obtained by expression of recombinant DNA in mammalian cells.

Human tissue-type plasminogen activator (t-PA), obtained by expression in mammalian cells of recombinant DNA coding for the entire sequence of t-PA (rt-PA), was compared with natural activator from melanoma cell culture (mt-PA). In an in vitro system, composed of [125I]fibrinogen-labeled plasma clot suspended in circulating human plasma, rt-PA and mt-PA caused a very similar dose-related degree of fibrinolysis without causing extensive fibrinolytic activation and fibrinogen breakdown in the surrounding plasma. Urokinase only induced fibrinolysis at a 5- to 10-fold higher concentration and in association with extensive fibrinogenolysis. Intravenous injection of mixtures of labeled (0.4 microCi/kg) and unlabeled (2000 I.U./kg) mt-PA or rt-PA resulted in a rapid but similar disappearance of activity from plasma (T1/2 of 3 min) and specific accumulation of tracer in the liver. In rabbits with experimental jugular vein thrombosis, rt-PA and mt-PA caused a very similar dose-dependent thrombolysis without causing substantial systemic activation of the fibrinolytic system and fibrinogenolysis. Urokinase induced significant thrombolysis only at a 10-fold higher dose and this was associated with systemic fibrinolytic activation. Infusion of 96,000 I.U./kg (approximately equal to 1 mg/kg) of mt-PA or rt-PA over 4 hr induced approximately 70% lysis, whereas a 10-fold higher dose of urokinase yielded 35 to 40% lysis. Two subfractions of rt-PA differing in the extent of glycosylation had very similar thrombolytic properties. It is concluded that the potentially more readily available rt-PA could constitute a specific, fibrin-selective thrombolytic agent.

Cell surface antigens of L-1210 leukemia recognized by monoclonal antibodies.

Conventional antisera to L-1210 leukemia were being prepared in our laboratory for nearly a decade and consistently the only specificity detectable was anti Mammary Leukemia antigen (ML). Serological analysis of five monoclonal antibodies obtained following the same immunization schedule showed more diverse pattern of reactivity. Two antigens detected belong to oncofetal category. The third one is differentiation antigen Ly-6 and the nature of two others, expressed on leukemic cells only, remains at present unclear. Thus none of the clones analysed produces antibodies to ML antigen. Our previous analysis of cell surface antigens of L-1210 leukemia with the use of conventional antisera has already been described. This paper presents the results of applying monoclonal antibodies in a comparable studies.

Experimental plasmacytoma in mice. II. Qualitative studies of myeloma proteins.

Qualitative studies on paraproteins present in ascites and/or in serum of mice with induced plasmacytoma were performed by the method of immunoelectrophoresis. Myeloma proteins were found in 75 out of 116 plasmacytomas. Among them in 53 cases production of IgA, in 6-IgG3, and in 1 case IgG was detected. In 10 out of 75 samples, two paraproteins present in one ascites were detected.

Experimental plasmacytoma in mice. I. Induction, morphological and biological characteristics.

The induction of plasmacytomas in BALB/c mice by Bayol F or Pristan is described. In some experiments mice treated with Bayol F were antigenically stimulated by repeated injections of allogenic C57BL/6 spleen cells. The incidence of plasmacytoma was 57% in Bayol F treated mice and 59% in the mice subjected to sustained antigenic stimulation. However, the tumors appeared about 6 months earlier in mice stimulated with the allogeneic spleen cells.