Performance Evaluation of Biozentech Malaria Scanner in Plasmodium knowlesi and P. falciparum as a New Diagnostic Tool

The computer vision diagnostic approach currently generates several malaria diagnostic tools. It enhances the accessible and straightforward diagnostics that necessary for clinics and health centers in malaria-endemic areas. A new computer malaria diagnostics tool called the malaria scanner was used to investigate living malaria parasites with easy sample preparation, fast and user-friendly. The cultured Plasmodium parasites were used to confirm the sensitivity of this technique then compared to fluorescence-activated cell sorting (FACS) analysis and light microscopic examination. The measured percentage of parasitemia by the malaria scanner revealed higher precision than microscopy and was similar to FACS. The coefficients of variation of this technique were 1.2-6.7% for Plasmodium knowlesi and 0.3-4.8% for P. falciparum. It allowed determining parasitemia levels of 0.1% or higher, with coefficient of variation smaller than 10%. In terms of the precision range of parasitemia, both high and low ranges showed similar precision results. Pearson’s correlation test was used to evaluate the correlation data coming from all methods. A strong correlation of measured parasitemia (r2=0.99, P<0.05) was observed between each method. The parasitemia analysis using this new diagnostic tool needs technical improvement, particularly in the differentiation of malaria species.

Performance Evaluation of Biozentech Malaria Scanner in Plasmodium knowlesi and P. falciparum as a New Diagnostic Tool

The computer vision diagnostic approach currently generates several malaria diagnostic tools. It enhances the accessible and straightforward diagnostics that necessary for clinics and health centers in malaria-endemic areas. A new computer malaria diagnostics tool called the malaria scanner was used to investigate living malaria parasites with easy sample preparation, fast and user-friendly. The cultured Plasmodium parasites were used to confirm the sensitivity of this technique then compared to fluorescence-activated cell sorting (FACS) analysis and light microscopic examination. The measured percentage of parasitemia by the malaria scanner revealed higher precision than microscopy and was similar to FACS. The coefficients of variation of this technique were 1.2-6.7% for Plasmodium knowlesi and 0.3-4.8% for P. falciparum. It allowed determining parasitemia levels of 0.1% or higher, with coefficient of variation smaller than 10%. In terms of the precision range of parasitemia, both high and low ranges showed similar precision results. Pearson’s correlation test was used to evaluate the correlation data coming from all methods. A strong correlation of measured parasitemia (r2=0.99, P<0.05) was observed between each method. The parasitemia analysis using this new diagnostic tool needs technical improvement, particularly in the differentiation of malaria species.

Diabetes Mellitus and COVID-19 / 임상당뇨병

Diabetes mellitus is known to be associated with more severe outcomes and increased mortality in patients presenting with coronavirus disease 2019 (COVID-19; severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) infection. The government driven so-called lock down strategy to prevent the spread of COVID-19 infection has changed not only social life styles but also disease related behaviors of diabetic patients. The mortality and morbidity of diabetic patients may be increasing during the COVID-19 pandemic. In this short article, I will describe this complex situation from the view-points of both diabetic patients and health care specialists, and offer several suggestions to solve these problems.

Diabetes Mellitus and COVID-19 / 임상당뇨병

Diabetes mellitus is known to be associated with more severe outcomes and increased mortality in patients presenting with coronavirus disease 2019 (COVID-19; severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) infection. The government driven so-called lock down strategy to prevent the spread of COVID-19 infection has changed not only social life styles but also disease related behaviors of diabetic patients. The mortality and morbidity of diabetic patients may be increasing during the COVID-19 pandemic. In this short article, I will describe this complex situation from the view-points of both diabetic patients and health care specialists, and offer several suggestions to solve these problems.

Breast Cancer Epidemiology of the Working-Age Female Population Reveals Significant Implications for the South Korean Economy / 한국유방암학회지

In this study, we aimed to evaluate the economic loss due to the diagnosis of breast cancer within the female South Korean working-age population. A population-based cost analysis was performed for cancer-related diagnoses between 1999 and 2014, using respective public government funded databases. Among the five most common cancers, breast cancer mortality was strongly associated with the growth in gross domestic product between 1999 and 2014 (R=0.98). In the female population, breast cancer represented the greatest productivity loss among all cancers, which was a consequence of the peak in the incidence of breast cancer during mid-working age in the working-age population, in addition to being the most common and fastest growing cancer among South Korean women. Our study shows that breast cancer not only represents a significant disease burden for individual patients, but also contributes a real, nonnegligible loss in productivity in the South Korean economy.

The Fate of Fracture Fragment in Diabetic Calcaneal Insufficiency Avulsion Fracture / 체질인류학회지

Diabetic calcaneal insufficiency avulsion (CIA) fracture are unusual injury. The treatment may be challenging due to the low healing potential from diabetes or Charcot neuroarthropathy, so far. The poor surgical outcomes and surgical failures from treatment of the traumatic calcaneal avulsion fractures were associated with poor bone stock, lack of proper fixation, and the wound problem. Thus, the proper treatment for diabetic CIA fracture was still controversy. This report described two cases of diabetic CIA fracture treated with fixation of fracture fragment and calcaneal tenodesis. In both cases, fracture fragments were re-avulsed despite of fixation. Through investigation for the fate of fracture fragment from these cases, we discussed the proper treatment strategy in diabetic CIA fracture.

Paradigm Changes in Diabetes Management Guidelines: American Diabetes Association 2018 / 임상당뇨병

The management of type 2 diabetes mellitus should comprise healthy lifestyle modifications along with tailored pharmacologic treatment. Traditionally, the American Diabetes Association (ADA)'s Diabetes Management Guidelines have not prioritized specific anti-diabetic drugs over others with regard to cardiovascular disease (CVD) and mortality prevention. Recently, two novel anti-diabetic medications proved to be significantly protective against future CVD and mortality, regardless of the glycemic levels achieved in type 2 diabetic patients with pre-existing CVD. The 2018 ADA Guidelines recommend SGLT2 inhibitor and/or GLP-1 receptor agonist be used for type 2 diabetes patients with atherosclerotic CVD after metformin monotherapy failure. Considering the value of CVD protection in the management of diabetes mellitus, this minor guideline adjustment could have far-reaching implications.

A Comparative Evaluation of Absorbable and Nonabsorbable Sutures for Open Repair of Achilles Tendon Rupture: A Pilot Study / 체질인류학회지

This pilot study was performed to compare the functional and clinical results including complications after surgery in the open repair of Achilles tendon rupture with regard to the type of suture material. A consecutive series of twenty patients with acute Achilles tendon rupture who underwent open repair were enrolled in this pilot study. The patients were divided equally into 2 groups according to suture type. In the nonabsorbable suture group, No. 2 braided nonabsorbable polyethylene terephthalate sutures were used, and in the absorbable suture group, braided absorbable polyglactin sutures were used. The Korean version of the Foot and Ankle Outcome Score (FAOS) and complications were assessed to evaluate functional and clinical result. Mean total Foot and Ankle Outcome Score (FAOS) was 89.8 (range, 71.1~100) in the nonabsorbable suture group and 82.7 (range, 61.9~92.5) in the absorbable suture group (p=0.22). All patients returned to their previous life activity. The absorbable suture group had fewer postoperative complications (10%) than the nonabsorbable suture group (20%), but there was no significant difference between two groups (p=0.45). This pilot study showed that use of an absorbable suture for Achilles tendon repair had functional and clinical results comparable to those of the nonabsorbable suture. However, a use of an absorbable suture was associated with a lower incidence of complications than the use of nonabsorbable suture. Therefore, these results have to be confirmed in a randomized controlled cohort trial with larger population.

Effects of Lobeglitazone, a Novel Thiazolidinedione, on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus over 52 Weeks

BACKGROUND: The aim of this multicenter, randomized, double-blind study was to examine the effect of lobeglitazone, a novel thiazolidinedione, on the changes in bone mineral density (BMD) in patients with type 2 diabetes mellitus. METHODS: A 24-week, double-blinded phase was followed by a 28-week, open-label phase, in which the placebo group also started to receive lobeglitazone. A total of 170 patients aged 34 to 76 years were randomly assigned in a 2:1 ratio to receive lobeglitazone 0.5 mg or a matching placebo orally, once daily. BMD was assessed using dual-energy X-ray absorptiometry at week 24 and at the end of the study (week 52). RESULTS: During the double-blinded phase, the femur neck BMD showed decreasing patterns in both groups, without statistical significance (−0.85%±0.36% and −0.78%±0.46% in the lobeglitazone and placebo groups, respectively). The treatment difference between the groups was 0.07%, which was also not statistically significant. Further, minimal, nonsignificant decreases were observed in both groups in the total hip BMD compared to values at baseline, and these differences also did not significantly differ between the groups. During the open-label phase, the BMD was further decreased, but not significantly, by −0.32% at the femur neck and by −0.60% at the total hip in the lobeglitazone group, and these changes did not significantly differ compared with the original placebo group switched to lobeglitazone. CONCLUSION: Our results indicate that treatment with lobeglitazone 0.5 mg over 52 weeks showed no detrimental effect on the BMD compared to the placebo.

Characterization of Pv92, a Novel Merozoite Surface Protein of Plasmodium vivax

The discovery and understanding of antigenic proteins are essential for development of a vaccine against malaria. In Plasmodium falciparum, Pf92 have been characterized as a merozoite surface protein, and this protein is expressed at the late schizont stage, but no study of Pv92, the orthologue of Pf92 in P. vivax, has been reported. Thus, the protein structure of Pv92 was analyzed, and the gene sequence was aligned with that of other Plasmodium spp. using bioinformatics tools. The recombinant Pv92 protein was expressed and purified using bacterial expression system and used for immunization of mice to gain the polyclonal antibody and for evaluation of antigenicity by protein array. Also, the antibody against Pv92 was used for subcellular analysis by immunofluorescence assay. The Pv92 protein has a signal peptide and a sexual stage s48/45 domain, and the cysteine residues at the N-terminal of Pv92 were completely conserved. The N-terminal of Pv92 was successfully expressed as soluble form using a bacterial expression system. The antibody raised against Pv92 recognized the parasites and completely merged with PvMSP1-19, indicating that Pv92 was localized on the merozoite surface. Evaluation of the human humoral immune response to Pv92 indicated moderate antigenicity, with 65% sensitivity and 95% specificity by protein array. Taken together, the merozoite surface localization and antigenicity of Pv92 implicate that it might be involved in attachment and invasion of a merozoite to a new host cell or immune evasion during invasion process.

Comparison of Vildagliptin and Pioglitazone in Korean Patients with Type 2 Diabetes Inadequately Controlled with Metformin

BACKGROUND: We compared the efficacies of vildagliptin (50 mg twice daily) relative to pioglitazone (15 mg once daily) as an add-on treatment to metformin for reducing glycosylated hemoglobin (HbA1c) levels in Korean patients with type 2 diabetes. METHODS: The present study was a multicenter, randomized, active-controlled investigation comparing the effects of vildagliptin and pioglitazone in Korean patients receiving a stable dose of metformin but exhibiting inadequate glycemic control. Each patient underwent a 16-week treatment period with either vildagliptin or pioglitazone as an add-on treatment to metformin. RESULTS: The mean changes in HbA1c levels from baseline were -0.94% in the vildagliptin group and -0.6% in the pioglitazone group and the difference between the treatments was below the non-inferiority margin of 0.3%. The mean changes in postprandial plasma glucose (PPG) levels were -60.2 mg/dL in the vildagliptin group and -38.2 mg/dL in the pioglitazone group and these values significantly differed (P=0.040). There were significant decreases in the levels of total, low density lipoprotein, high density lipoprotein (HDL), and non-HDL cholesterol in the vildagliptin group but increases in the pioglitazone group. The mean change in body weight was -0.07 kg in the vildagliptin group and 0.69 kg in the pioglitazone group, which were also significantly different (P=0.002). CONCLUSION: As an add-on to metformin, the efficacy of vildagliptin for the improvement of glycemic control is not inferior to that of pioglitazone in Korean patients with type 2 diabetes. In addition, add-on treatment with vildagliptin had beneficial effects on PPG levels, lipid profiles, and body weight compared to pioglitazone.

Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor

BACKGROUND: Cognitive impairment and brain damage in diabetes is suggested to be associated with hypoglycemia. The mechanisms of hypoglycemia-induced neural death and apoptosis are not clear and reperfusion injury may be involved. Recent studies show that glucose deprivation/reperfusion induced more neuronal cell death than glucose deprivation itself. The forkhead box O (FOXO) transcription factors are implicated in the regulation of cell apoptosis and survival, but their role in neuronal cells remains unclear. We examined the role of FOXO transcription factors and the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt and apoptosis-related signaling pathways in PC-12 cells exposed to repeated glucose deprivation/reperfusion. METHODS: PC-12 cells were exposed to control (Dulbecco's Modified Eagle Medium [DMEM] containing 25 mM glucose) or glucose deprivation/reperfusion (DMEM with 0 mM glucose for 6 hours and then DMEM with 25 mM glucose for 18 hours) for 5 days. MTT assay and Western blot analysis were performed for cell viability, apoptosis, and the expression of survival signaling pathways. FOXO3/4',6-diamidino-2-phenylindole staining was done to ascertain the involvement of FOXO transcription factors in glucose deprivation/reperfusion conditions. RESULTS: Compared to PC-12 cells not exposed to hypoglycemia, cells exposed to glucose deprivation/reperfusion showed a reduction of cell viability, decreased expression of phosphorylated Akt and Bcl-2, and an increase of cleaved caspase-3 expression. Of note, FOXO3 protein was localized in the nuclei of glucose deprivation/reperfusion cells but not in the control cells. CONCLUSION: Repeated glucose deprivation/reperfusion caused the neuronal cell death. Activated FOXO3 via the PI3K/Akt pathway in repeated glucose deprivation/reperfusion was involved in genes related to apoptosis.

Postoperative Clinical Outcome and Risk Factors for Poor Outcome of Foraminal and Extraforaminal Lumbar Disc Herniation

OBJECTIVE: We evaluated postoperative outcomes in patients who have lumbar foraminal or extraforaminal disc herniation (FELDH) and suggested the risk factors for poor outcomes. METHODS: A total of 234 patients were selected for this study. Pre- and post-operative Visual Analogue Scale (VAS) and Korean version Oswestry Disability Index (KODI) were evaluated and the changes of both score were calculated. Outcome was defined as excellent, good, fair, and poor based on Mcnab classification. The percentage of superior facetectomy was calculated by using the Maro-view 5.4 Picture Archiving Communication System (PACS). RESULTS: Paramedian lumbar discectomy was performed in 180 patients and combined lumbar discectomy was performed in 54 patients. Paramedian lumbar discectomy group showed better outcome compared with combined discectomy group. p value of VAS change was 0.009 and KODI was 0.013. The average percentage of superior facetectomy was 33% (range, 0-79%) and it showed negative correlation with VAS and KODI changes (Pearson coefficient : -0.446 and -0.498, respectively). Excellent or good outcome cases (Group I) were 136 (58.1%) and fair or poor outcome cases (Group II) were 98 (41.9%). The percentage of superior facetectomy was 26.5% at Group I and 42.5% at Group II. There was significant difference in superior facetectomy percentage between Group I and II (p=0.000). CONCLUSION: This study demonstrated that paramedian lumbar discectomy with preservation of facet joints is an effective and good procedure for FELDH. At least 60% of facet should be preserved for excellent or good outcomes.

A Case of Fulminant Type 1 Diabetes during Pregnancy / 임상당뇨병

Fulminant type 1 diabetes is characterized by acute onset, no evidence of islet-related autoantibodies, low glycated hemoglobin(HbA1c) level at onset, and metabolic complications such as diabetic ketoacidosis. Fulminant type 1 diabetes development during pregnancy can result in severe maternal and fetal complications. Most of the patients with fulminant type 1 diabetes during pregnancy have been reported in Japan. In Korea, reports of fulminant type 1 diabetes during pregnancy are uncommon. We report a 36-year-old Korean woman with fulminant type 1 diabetes developed at 32 weeks of gestation who demonstrate a good outcome.

Efficacy of a Once-Monthly Pill Containing Ibandronate and Cholecalciferol on the Levels of 25-Hydroxyvitamin D and Bone Markers in Postmenopausal Women with Osteoporosis

BACKGROUND: The present study evaluated the efficacy of a combination of ibandronate and cholecalciferol on the restoration of the levels of 25-hydroxyvitamin D (25[OH]D) and various bone markers in postmenopausal women with osteoporosis. METHODS: This was a randomized, double-blind, active-controlled, prospective 16-week clinical trial conducted in 20 different hospitals. A total of 201 postmenopausal women with osteoporosis were assigned randomly to one of two groups: the IBN group, which received a once-monthly pill containing 150 mg ibandronate (n=99), or the IBN+ group, which received a once-monthly pill containing 150 mg ibandronate and 24,000 IU cholecalciferol (n=102). Serum levels of 25(OH)D, parathyroid hormone (PTH), and various bone markers were assessed at baseline and at the end of a 16-week treatment period. RESULTS: After 16 weeks of treatment, the mean serum levels of 25(OH)D significantly increased from 21.0 to 25.3 ng/mL in the IBN+ group but significantly decreased from 20.6 to 17.4 ng/mL in the IBN group. Additionally, both groups exhibited significant increases in mean serum levels of PTH but significant decreases in serum levels of bone-specific alkaline phosphatase and C-telopeptide of type 1 collagen (CTX) at 16 weeks; no significant differences were observed between the groups. However, in subjects with a vitamin D deficiency, IBN+ treatment resulted in a significant decrease in serum CTX levels compared with IBN treatment. CONCLUSION: The present findings demonstrate that a once-monthly pill containing ibandronate and cholecalciferol may be useful for the amelioration of vitamin D deficiency in patients with postmenopausal osteoporosis. Moreover, this treatment combination effectively decreased serum levels of resorption markers, especially in subjects with a vitamin D deficiency, over the 16-week treatment period.

Co-Culture of alpha TC-6 Cells and beta TC-1 Cells: Morphology and Function

BACKGROUND: In vitro experiments using only beta-cell lines instead of islets are limited because pancreatic islets are composed of four different types of endocrine cells. Several recent studies have focused on cellular interactions among these cell types, especially alpha- and beta-cells. Because islet isolation needs time and experience, we tested a simple co-culture system with alpha- and beta-cells. Their morphology and function were assessed by comparison to each single cell culture and pancreatic islets. METHODS: alpha TC-6 cells and beta TC-1 cells were maintained in Dulbecco's Minimal Essential Medium containing 5 mM glucose and 10% fetal bovine serum. Cells were mixed at a 1:1 ratio (5x10(5)) in 6-well plates and cultured for 24, 48, and 72 hours. After culture, cells were used for insulin and glucagon immunoassays and tested for glucose-stimulated insulin secretion (GSIS). RESULTS: alpha TC-6 and beta TC-1 cells became condensed by 24 hours and were more strongly compacted after 48 hours. beta TC-1 cells showed both beta-beta and beta-alpha cell contacts. GSIS increased with increasing glucose concentration in co-cultured cells, which showed lower secreted insulin levels than beta TC-1 cells alone. The increase in the secreted insulin/insulin content ratio was significantly lower for co-cultured cells than for beta-cells alone (P=0.04). Compared to islets, the alpha-/beta-cell co-culture showed a higher ratio of GSIS to insulin content, but the difference was not statistically significant (P=0.09). CONCLUSION: alpha TC-6 and beta TC-1 cells in the co-culture system showed cell-to-cell contacts and a similar stimulated insulin secretion pattern to islets. The co-culture system may be used to better mimic pancreatic islets in in vitro assessments.

Identification of Immunodominant B-cell Epitope Regions of Reticulocyte Binding Proteins in Plasmodium vivax by Protein Microarray Based Immunoscreening

Plasmodium falciparum can invade all stages of red blood cells, while Plasmodium vivax can invade only reticulocytes. Although many P. vivax proteins have been discovered, their functions are largely unknown. Among them, P. vivax reticulocyte binding proteins (PvRBP1 and PvRBP2) recognize and bind to reticulocytes. Both proteins possess a C-terminal hydrophobic transmembrane domain, which drives adhesion to reticulocytes. PvRBP1 and PvRBP2 are large (> 326 kDa), which hinders identification of the functional domains. In this study, the complete genome information of the P. vivax RBP family was thoroughly analyzed using a prediction server with bioinformatics data to predict B-cell epitope domains. Eleven pvrbp family genes that included 2 pseudogenes and 9 full or partial length genes were selected and used to express recombinant proteins in a wheat germ cell-free system. The expressed proteins were used to evaluate the humoral immune response with vivax malaria patients and healthy individual serum samples by protein microarray. The recombinant fragments of 9 PvRBP proteins were successfully expressed; the soluble proteins ranged in molecular weight from 16 to 34 kDa. Evaluation of the humoral immune response to each recombinant PvRBP protein indicated a high antigenicity, with 38-88% sensitivity and 100% specificity. Of them, N-terminal parts of PvRBP2c (PVX_090325-1) and PvRBP2 like partial A (PVX_090330-1) elicited high antigenicity. In addition, the PvRBP2-like homologue B (PVX_116930) fragment was newly identified as high antigenicity and may be exploited as a potential antigenic candidate among the PvRBP family. The functional activity of the PvRBP family on merozoite invasion remains unknown.

A Case of Type 2 Diabetes Mellitus Initially Presented as Monochorea Associated with Ketotic Hyperglycemia / 임상당뇨병

Monoballismus-monochorea is abnormal neurologic sign characterized by continuous, involuntary and irregular movement involving one extremity. Hyperglycemic ballism-chorea is predominantly observed in older type 2 diabetic patients and non-ketotic hyperglycemia, and is associated with contralateral striatal hyperintensities (i.e., putamen and caudate) on both brain CT and MRI. Movement disorders as the initial symptoms of diabetes mellitus are rare, especially in ketotic hyperglycemia. Here, we report one of these rare manifestations of transient monoballismus with during an episode of ketotic hyperglycemia without contralateral striatal abnormal findings on brain MRI in newly diagnosed diabetes mellitus.

The Effects of Therapeutic Lifestyle Change on Cardiovascular Disease and Mortality in Diabetic Patients / 임상당뇨병

The universal first step for the treatment of diabetes mellitus, hypertension, dyslipidemia or atherosclerotic disease is therapeutic lifestyle change (TLC). However, in most cases, long-term sincere maintenance of TLC is very difficult. The Look-AHEAD study was initiated based on the results of the Diabetes Prevention Program (DPP) trial that evaluated the effects of TLC on the prevention of diabetes. However, the look-AHEAD trial failed to demonstrate the benefit of intensive lifestyle intervention (ILI) for the prevention of CVD or CVD-associated mortality. Several explanations were suggested, including that the ILI group did not maintain effective weight loss, and that the intervention and control groups both received the same high-quality medical treatments. The participants of the look-AHEAD trial were very highly motivated, and the investigators of the trial systematically pursued their patients to achieve the desired end result, which is quite different from the usual clinical practice setting. Simple advisement for patients to perform diet restriction and moderate intensity regular physical exercise typically fails and is ineffective for the prevention of CVD in actual clinical practice. Concomitant sincere control of other risk factors is necessary for long-term CVD prevention. Further research on practical and effective methods for achievement of successful TLC is needed.

Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitor / 대한내과학회지

Sodium glucose co-transporter 2 (SGLT2) inhibition is a new therapeutic approach for the treatment of type 2 diabetes mellitus, independent of insulin secretion and activity. SGLT2 inhibitors have a unique mechanism of action via inhibition of renal glucose reabsorption, which is different from the mechanisms of prior medications. Clinical trials have supported the efficacy of SGLT2 inhibitors in the reduction of HbA1c as monotherapy or add-on therapy with other existing medications, including insulin. In addition to their glucose-lowering effect, SGLT2 inhibitors can significantly reduce blood pressure and body weight. The most concerning side effects are genital and urinary tract infections, especially in females. SGLT2 inhibitors offer a promising potential strategy for diabetes treatment because they can be combined with nearly any existing anti-diabetic medication, cause less hypoglycemia, and possess additional metabolic benefits beyond glucose level reduction.