Poly(l-threonine-co-l-threonine Succinate) Thermogels for Sustained Release of Lixisenatide.

Negatively charged poly(l-Thr-co-l-Thr succinate) (PTTs) was developed as a new thermogel. Aqueous PTT solutions underwent thermogelation over a concentration range of 6.0-8.3 wt %. Dynamic light scattering, FTIR, 1H NMR, and COSY spectra revealed the partial strengthening of the ß-sheet conformation and the dehydration of PTTs during the transition. Extendin-4 was released from the PTTs thermogel with a large initial burst release, whereas positively charged lixisenatide significantly reduced its initial burst release to 25%, and up to 77% of the dose was released from the gel over 14 days. In vivo study revealed a high plasma concentration of lixisenatide over 5 days and hypoglycemic efficacy was observed for type II diabetic rats over 7-10 days. The biocompatible PTTs were degraded by subcutaneous enzymes. This study thus demonstrates an effective strategy for reducing the initial burst release of protein drugs from thermogels with the introduction of electrostatic interactions between the drug and the thermogel.

Oligonucleotides as Inhibitors of Ice Recrystallization.

Oligonucleotides of adenine (A20), guanine (G20), cytosine (C20), thymine (T20), cytosine-guanine ((CG)20), and adenine-thymine ((AT)20) were investigated as model compounds for ice recrystallization inhibition (IRI). Dehydroxy uracil (dU20), U20, and T20 were also compared to investigate the effect of minute changes in the hydrophobicity of the oligonucleotides on the IRI activity. Among the oligonucleotides considered in this study, T20 exhibited the best performance for IRI. In addition, the degree of polymerization of oligothymines varied over 5, 10, 20, 30, 50, and 100, and T20 was found to be the most effective for IRI. The IRI mechanism was investigated by comparing U20 and T20, which exhibited the lowest and highest IRI activity, respectively, among the oligonucleotides for their dynamic ice-shaping, thermal hysteresis, and ice nucleation inhibition. Little or no dynamic ice-shaping activity and small thermal hysteresis were observed for both nucleotides. All of the findings suggest that not the ice-polymer adhesion but the hydrophobic interactions of T20 in the interface layer might interfere with the water deposition on the ice crystal surfaces and contribute to the IRI activity of the T20 oligonucleotide.

Poly(l-alanine-co-l-lysine)-g-Trehalose as a Biomimetic Cryoprotectant for Stem Cells.

Poly(l-alanine-co-l-lysine)-graft-trehalose (PAKT) was synthesized as a natural antifreezing glycopolypeptide (AFGP)-mimicking cryoprotectant for cryopreservation of mesenchymal stem cells (MSCs). FTIR and circular dichroism spectra indicated that the content of the α-helical structure of PAK decreased after conjugation with trehalose. Two protocols were investigated in cryopreservation of MSCs to prove the significance of the intracellularly delivered PAKT. In protocol I, MSCs were cryopreserved at -196 °C for 7 days by a slow-cooling procedure in the presence of both PAKT and free trehalose. In protocol II, MSCs were preincubated at 37 °C in a PAKT solution, followed by cryopreservation at -196 °C in the presence of free trehalose for 7 days by the slow-cooling procedure. Polymer and trehalose concentrations were varied by 0.0-1.0 and 0.0-15.0 wt %, respectively. Cell recovery was significantly improved by protocol II with preincubation of the cells in the PAKT solution. The recovered cells from protocol II exhibited excellent proliferation and maintained multilineage potentials into osteogenic, chondrogenic, and adipogenic differentiation, similar to MSCs recovered from cryopreservation in the traditional 10% dimethyl sulfoxide system. Ice recrystallization inhibition (IRI) activity of the polymers/trehalose contributed to cell recovery; however, intracellularly delivered PEG-PAKT was the major contributor to the enhanced cell recovery in protocol II. Inhibitor studies suggested that macropinocytosis and caveolin-dependent endocytosis are the main mechanisms for the intracellular delivery of PEG-PAKT. 1H NMR and FTIR spectra suggested that the intracellular PEG-PAKTs interact with water and stabilize the cells during cryopreservation.

Hypothermic Stem Cell Storage Using a Polypeptide Thermogel.

We report a polypeptide-based thermogel as a new tool for hypothermic storage of stem cells at ambient temperature (25 °C). Stem cells were suspended in the sol state (10 °C) of an aqueous poly(ethylene glycol)-poly(l-alanine) (PEG-PA) solution (4.0 wt %) in phosphate-buffered saline (PBS), which turned into a stem cell-incorporated gel by a heat-induced sol-to-gel transition. The cell harvesting procedure from the thermogels was simply performed through a gel-to-sol transition by diluting and cooling the system. More than 99% of stem cells died in PBS and Pluronic F127 thermogel (control thermogel) when the cells were stored at 25 °C for 7 days. The cell recovery rate from the PEG-PA thermogel (64%) was significantly greater than that from the commercially available HypoThermosol FRS preservation solution (HTS) (26%). Additionally, the surviving stem cells from the PEG-PA thermogel were healthier than those from HTS in terms of (1) expression of stemness biomarkers (NANOG, OCT4, and SOX2), (2) proliferation rate, and (3) differentiation potentials into osteogenic, chondrogenic, and adipogenic lineages. Membrane stabilization was suggested as a cell protection mechanism in the cytocompatible PEG-PA thermogel. The PEG-PA thermogel provides a convenient cytocompatible way for the storage and recovery of cells and thus is a promising tool for the transportation and short-term banking of cells.

Acute Febrile Illness Among Children in Butajira, South-Central Ethiopia During the Typhoid Fever Surveillance in Africa Program.

BACKGROUND: Clearly differentiating causes of fever is challenging where diagnostic capacities are limited, resulting in poor patient management. We investigated acute febrile illness in children aged ≤15 years enrolled at healthcare facilities in Butajira, Ethiopia, during January 2012 to January 2014 for the Typhoid Fever Surveillance in Africa Program. METHODS: Blood culture, malaria microscopy, and blood analyses followed by microbiological, biochemical, and antimicrobial susceptibility testing of isolates were performed. We applied a retrospectively developed scheme to classify children as malaria or acute respiratory, gastrointestinal or urinary tract infection, or other febrile infections and syndromes. Incidence rates per 100 000 population derived from the classification scheme and multivariate logistic regression to determine fever predictors were performed. RESULTS: We rarely observed stunting (4/513, 0.8%), underweight (1/513, 0.2%), wasting (1/513, 0.2%), and hospitalization (21/513, 4.1%) among 513 children with mild transient fever and a mean disease severity score of 12 (95% confidence interval [CI], 11-13). Blood cultures yielded 1.6% (8/513) growth of pathogenic agents; microscopy detected 13.5% (69/513) malaria with 20 611/µL blood (95% CI, 15 352-25 870) mean parasite density. Incidences were generally higher in children aged ≤5 years than >5 to ≤15 years; annual incidences in young children were 301.3 (95% CI, 269.2-337.2) for malaria and 1860.1 (95% CI, 1778.0-1946.0) for acute respiratory and 379.9 (95% CI, 343.6-420.0) for gastrointestinal tract infections. CONCLUSIONS: We could not detect the etiological agents in all febrile children. Our findings may prompt further investigations and the reconsideration of policies and frameworks for the management of acute febrile illness.

The Typhoid Fever Surveillance in Africa Program: Geospatial Sampling Frames for Household-based Studies: Lessons Learned From a Multicountry Surveillance Network in Senegal, South Africa, and Sudan.

BACKGROUND: Robust household sampling, commonly applied for population-based investigations, requires sampling frames or household lists to minimize selection bias. We have applied Google Earth Pro satellite imagery to constitute structure-based sampling frames at sites in Pikine, Senegal; Pietermaritzburg, South Africa; and Wad-Medani, Sudan. Here we present our experiences in using this approach and findings from assessing its applicability by determining positional accuracy. METHODS: Printouts of satellite imagery combined with Global Positioning System receivers were used to locate and to verify the locations of sample structures (simple random selection; weighted-stratified sampling). Positional accuracy was assessed by study site and administrative subareas by calculating normalized distances (meters) between coordinates taken from the sampling frame and on the ground using receivers. A higher accuracy in conjunction with smaller distances was assumed. Kruskal-Wallis and Dunn multiple pairwise comparisons were performed to evaluate positional accuracy by setting and by individual surveyor in Pietermaritzburg. RESULTS: The median normalized distances and interquartile ranges were 0.05 and 0.03-0.08 in Pikine, 0.09 and 0.05-0.19 in Pietermaritzburg, and 0.05 and 0.00-0.10 in Wad-Medani, respectively. Root mean square errors were 0.08 in Pikine, 0.42 in Pietermaritzburg, and 0.17 in Wad-Medani. Kruskal-Wallis and Dunn comparisons indicated significant differences by low- and high-density setting and interviewers who performed the presented approach with high accuracy compared to interviewers with poor accuracy. CONCLUSIONS: The geospatial approach presented minimizes systematic errors and increases robustness and representativeness of a sample. However, the findings imply that this approach may not be applicable at all sites and settings; its success also depends on skills of surveyors working with aerial data. Methodological modifications are required, especially for resource-challenged sites that may be affected by constraints in data availability and area size.

Multicountry Distribution and Characterization of Extended-spectrum ß-Lactamase-associated Gram-negative Bacteria From Bloodstream Infections in Sub-Saharan Africa.

BACKGROUND: Antimicrobial resistance (AMR) is a major global health concern, yet, there are noticeable gaps in AMR surveillance data in regions such as sub-Saharan Africa. We aimed to measure the prevalence of extended-spectrum ß-lactamase (ESBL) producing Gram-negative bacteria in bloodstream infections from 12 sentinel sites in sub-Saharan Africa. METHODS: Data were generated during the Typhoid Fever Surveillance in Africa Program (TSAP), in which standardized blood cultures were performed on febrile patients attending 12 health facilities in 9 sub-Saharan African countries between 2010 and 2014. Pathogenic bloodstream isolates were identified at the sites and then subsequently confirmed at a central reference laboratory. Antimicrobial susceptibility testing, detection of ESBL production, and conventional multiplex polymerase chain reaction (PCR) testing for genes encoding for ß-lactamase were performed on all pathogens. RESULTS: Five hundred and five pathogenic Gram-negative bloodstream isolates were isolated during the study period and available for further characterization. This included 423 Enterobacteriaceae. Phenotypically, 61 (12.1%) isolates exhibited ESBL activity, and genotypically, 47 (9.3%) yielded a PCR amplicon for at least one of the screened ESBL genes. Among specific Gram-negative isolates, 40 (45.5%) of 88 Klebsiella spp., 7 (5.7%) of 122 Escherichia coli, 6 (16.2%) of 37 Acinetobacter spp., and 2 (1.3%) of 159 of nontyphoidal Salmonella (NTS) showed phenotypic ESBL activity. CONCLUSIONS: Our findings confirm the presence of ESBL production among pathogens causing bloodstream infections in sub-Saharan Africa. With few alternatives for managing ESBL-producing pathogens in the African setting, measures to control the development and proliferation of AMR organisms are urgently needed.

Efficacy of a bivalent killed whole-cell cholera vaccine over five years: a re-analysis of a cluster-randomized trial.

BACKGROUND: Oral cholera vaccine (OCV) is a feasible tool to prevent or mitigate cholera outbreaks. A better understanding of the vaccine's efficacy among different age groups and how rapidly its protection wanes could help guide vaccination policy. METHODS: To estimate the level and duration of OCV efficacy, we re-analyzed data from a previously published cluster-randomized, double-blind, placebo controlled trial with five years of follow-up. We used a Cox proportional hazards model and modeled the potentially time-dependent effect of age categories on both vaccine efficacy and risk of infection in the placebo group. In addition, we investigated the impact of an outbreak period on model estimation. RESULTS: Vaccine efficacy was 38% (95% CI: -2%,62%) for those vaccinated from ages 1 to under 5 years old, 85% (95% CI: 67%,93%) for those 5 to under 15 years, and 69% (95% CI: 49%,81%) for those vaccinated at ages 15 years and older. Among adult vaccinees, efficacy did not appear to wane during the trial, but there was insufficient data to assess the waning of efficacy among child vaccinees. CONCLUSIONS: Through this re-analysis we were able to detect a statistically significant difference in OCV efficacy when the vaccine was administered to children under 5 years old vs. children 5 years and older. The estimated efficacies are more similar to the previously published analysis based on the first two years of follow-up than the analysis based on all five years. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00289224.

Psychological impact of the 2015 MERS outbreak on hospital workers and quarantined hemodialysis patients.

OBJECTIVES: This study aimed to assess the immediate stress and psychological impact experienced by quarantined patients undergoing hemodialysis and university hospital workers who treated patients Middle East respiratory syndrome (MERS) during its outbreak. DESIGN: The group of subjects consisted of 1800 hospital practitioners and 73 quarantined patients undergoing hemodialysis. The Impact of Events Scale-Revised (IES-R) was administered to the practitioners twice, once during the hospital shutdown and again one month after the shutdown. The Mini International Neuropsychiatric Interview and Hospital Anxiety and Depression Scale were administered to patients undergoing hemodialysis. RESULTS: During the initial stages of the MERS outbreak, healthcare workers who performed MERS-related tasks scored significantly higher on the total IES-R and its subscales. In the second assessment of the high-risk group, the sleep and numbness subscale scores from the IES-R differed depending on the implementation of home quarantine, and the intrusion subscale scores differed depending on the performance of MERS-related tasks. CONCLUSION: Medical staff that performed MERS-related tasks showed the highest risk for post-traumatic stress disorder symptoms even after time had elapsed. The risk increased even after home quarantine. Prompt and continuous psychiatric intervention is needed in high mortality infectious disease outbreaks.

Variations of Invasive Salmonella Infections by Population Size in Asante Akim North Municipal, Ghana.

BACKGROUND: The Typhoid Fever Surveillance in Africa Program (TSAP) estimated adjusted incidence rates (IRs) for Salmonella enterica serovar Typhi and invasive nontyphoidal S. enterica serovars (iNTS) of >100 cases per 100 000 person-years of observation (PYO) for children aged <15 years in Asante Akim North Municipal (AAN), Ghana, between March 2010 and May 2012. We analyzed how much these rates differed between rural and urban settings. METHODS: Children recruited at the Agogo Presbyterian Hospital and meeting TSAP inclusion criteria were included in the analysis. Towns with >32 000 inhabitants were considered urban; towns with populations <5200 were considered rural. Adjusted IRs for Salmonella bloodstream infections were estimated for both settings. Setting-specific age-standardized incidence rates for children aged <15 years were derived and used to calculate age-standardized rate ratios (SRRs) to evaluate differences between settings. RESULTS: Eighty-eight percent (2651/3000) of recruited patients met inclusion criteria and were analyzed. IRs of Salmonella bloodstream infections in children <15 years old were >100 per 100 000 PYO in both settings. Among rural children, the Salmonella Typhi and iNTS rates were 2 times (SRR, 2.2; 95% confidence interval [CI], 1.3-3.5) and almost 3 times (SRR, 2.8; 95% CI, 1.9-4.3) higher, respectively, than rates in urban children. CONCLUSIONS: IRs of Salmonella bloodstream infections in children <15 years old in AAN, Ghana, differed by setting, with 2 to nearly 3 times higher rates in the less populated setting. Variations in the distribution of the disease should be considered to implement future studies and intervention strategies.

Utilization of Healthcare in the Typhoid Fever Surveillance in Africa Program.

BACKGROUND: Assessing healthcare utilization is important to identify weaknesses of healthcare systems, to outline action points for preventive measures and interventions, and to more accurately estimate the disease burden in a population. METHODS: A healthcare utilization survey was developed for the Typhoid Fever Surveillance in Africa Program (TSAP) to adjust incidences of salmonellosis determined through passive, healthcare facility-based surveillance. This cross-sectional survey was conducted at 11 sites in 9 sub-Saharan African countries. Demographic data and healthcare-seeking behavior were assessed at selected households. Overall and age-stratified percentages of each study population that sought healthcare at a TSAP healthcare facility and elsewhere were determined. RESULTS: Overall, 88% (1007/1145) and 81% (1811/2238) of the population in Polesgo and Nioko 2, Burkina Faso, respectively, and 63% (1636/2590) in Butajira, Ethiopia, sought healthcare for fever at any TSAP healthcare facility. A far smaller proportion-namely, 20%-45% of the population in Bissau, Guinea-Bissau (1743/3885), Pikine, Senegal (1473/4659), Wad-Medani, Sudan (861/3169), and Pietermaritzburg, South Africa (667/2819); 18% (483/2622) and 9% (197/2293) in Imerintsiatosika and Isotry, Madagascar, respectively; and 4% (127/3089) in Moshi, Tanzania-sought healthcare at a TSAP healthcare facility. Patients with fever preferred to visit pharmacies in Imerintsiatosika and Isotry, and favored self-management of fever in Moshi. Age-dependent differences in healthcare utilization were also observed within and across sites. CONCLUSIONS: Healthcare utilization for fever varied greatly across sites, and revealed that not all studied populations were under optimal surveillance. This demonstrates the importance of assessing healthcare utilization. Survey data were pivotal for the adjustment of the program's estimates of salmonellosis and other conditions associated with fever.

The Relationship Between Invasive Nontyphoidal Salmonella Disease, Other Bacterial Bloodstream Infections, and Malaria in Sub-Saharan Africa.

BACKGROUND: Country-specific studies in Africa have indicated that Plasmodium falciparum is associated with invasive nontyphoidal Salmonella (iNTS) disease. We conducted a multicenter study in 13 sites in Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania to investigate the relationship between the occurrence of iNTS disease, other systemic bacterial infections, and malaria. METHODS: Febrile patients received a blood culture and a malaria test. Isolated bacteria underwent antimicrobial susceptibility testing, and the association between iNTS disease and malaria was assessed. RESULTS: A positive correlation between frequency proportions of malaria and iNTS was observed (P = .01; r = 0.70). Areas with higher burden of malaria exhibited higher odds of iNTS disease compared to other bacterial infections (odds ratio [OR], 4.89; 95% CI, 1.61-14.90; P = .005) than areas with lower malaria burden. Malaria parasite positivity was associated with iNTS disease (OR, 2.44; P = .031) and gram-positive bacteremias, particularly Staphylococcus aureus, exhibited a high proportion of coinfection with Plasmodium malaria. Salmonella Typhimurium and Salmonella Enteritidis were the predominant NTS serovars (53/73; 73%). Both moderate (OR, 6.05; P = .0001) and severe (OR, 14.62; P < .0001) anemia were associated with iNTS disease. CONCLUSIONS: A positive correlation between iNTS disease and malaria endemicity, and the association between Plasmodium parasite positivity and iNTS disease across sub-Saharan Africa, indicates the necessity to consider iNTS as a major cause of febrile illness in malaria-holoendemic areas. Prevention of iNTS disease through iNTS vaccines for areas of high malaria endemicity, targeting high-risk groups for Plasmodium parasitic infection, should be considered.

Potential involvement of NET polymorphism in serotonin/norepinephrine reuptake inhibitor response in panic disorder.

BACKGROUND: This is a pilot study assessing the impact of polymorphisms of serotonin transporter (5-HTT; 5-HTTLPR (S/L)) and norepinephrine transporter (NET; rs2242446 (T/C)) genes on selective serotonin reuptake inhibitors (SSRIs) and serotonin/norepinephrine reuptake inhibitors (SNRIs) response in Korean panic disorder (PD) patients. METHODS: PD patients were treated with SSRI (n = 18) or SNRI (n = 6) for 4 weeks. Panic Disorder Severity Scale (PDSS) was rated to evaluate the treatment response. Wilcoxon signed-rank test was used to compare PDSS scores before and after medication (SSRI or SNRI) as well as to compare those according to genotypes. Mann-Whitney U test was used to compare those between the two groups (SSRI or SNRI). RESULTS: Both SSRI and SNRI treatments for 4 weeks significantly reduced PDSS scores. We assessed the impact of rs2242446 on this effect of SSRI and SNRI. The scores were significantly decreased after 4 weeks in the SSRI-treated group regardless of genotypes of rs2242446, whereas they were significantly decreased in the SNRI-treated group with only non-C carrier (TT) of rs2242446. On 5-HTTLPR we could not analyse because 22 patients had SS genotype. CONCLUSIONS: These results suggest that NET polymorphism may affect the SNRI response in Korean PD patients.

Association between IRS1 Gene Polymorphism and Autism Spectrum Disorder: A Pilot Case-Control Study in Korean Males.

The insulin-like growth factor (IGF) pathway is thought to play an important role in brain development. Altered levels of IGFs and their signaling regulators have been shown in autism spectrum disorder (ASD) patients. In this study, we investigated whether coding region single-nucleotide polymorphisms (cSNPs) of the insulin receptor substrates (IRS1 and IRS2), key mediators of the IGF pathway, were associated with ASD in Korean males. Two cSNPs (rs1801123 of IRS1, and rs4773092 of IRS2) were genotyped using direct sequencing in 180 male ASD patients and 147 male control subjects. A significant association between rs1801123 of IRS1 and ASD was shown in additive (p = 0.022, odds ratio (OR) = 0.66, 95% confidence interval (CI) = 0.46-0.95) and dominant models (p = 0.013, OR = 0.57, 95% CI = 0.37-0.89). Allele frequency analysis also showed an association between rs1801123 and ASD (p = 0.022, OR = 0.66, 95% CI = 0.46-0.94). These results suggest that IRS1 may contribute to the susceptibility of ASD in Korean males.

Bloodstream Infections and Frequency of Pretreatment Associated With Age and Hospitalization Status in Sub-Saharan Africa.

BACKGROUND: The clinical diagnosis of bacterial bloodstream infections (BSIs) in sub-Saharan Africa is routinely confused with malaria due to overlapping symptoms. The Typhoid Surveillance in Africa Program (TSAP) recruited febrile inpatients and outpatients of all ages using identical study procedures and enrollment criteria, thus providing an opportunity to assess disease etiology and pretreatment patterns among children and adults. METHODS: Inpatients and outpatients of all ages with tympanic or axillary temperatures of ≥38.0 or ≥37.5°C, respectively, and inpatients only reporting fever within the previous 72 hours were eligible for recruitment. All recruited patients had one blood sample drawn and cultured for microorganisms. Data from 11 TSAP surveillance sites in nine different countries were used in the analysis. Bivariate analysis was used to compare frequencies of pretreatment and BSIs in febrile children (<15 years old) and adults (≥15 years old) in each country. Pooled Cochran Mantel-Haenszel odds ratios (ORs) were calculated for overall trends. RESULTS: There was no significant difference in the odds of a culture-proven BSI between children and adults among inpatients or outpatients. Among both inpatients and outpatients, children had significantly higher odds of having a contaminated blood culture compared with adults. Using country-pooled data, child outpatients had 66% higher odds of having Salmonella Typhi in their bloodstream than adults (OR, 1.66; 95% confidence interval [CI], 1.01-2.73). Overall, inpatient children had 59% higher odds of pretreatment with analgesics in comparison to inpatient adults (OR, 1.59; 95% CI, 1.28-1.97). CONCLUSIONS: The proportion of patients with culture-proven BSIs in children compared with adults was similar across the TSAP study population; however, outpatient children were more likely to have Salmonella Typhi infections than outpatient adults. This finding points to the importance of including outpatient facilities in surveillance efforts, particularly for the surveillance of typhoid fever. Strategies to reduce contamination among pediatric blood cultures are needed across the continent to prevent the misdiagnosis of BSI cases in children.

A model immunization programme to control Japanese encephalitis in Viet Nam.

In Viet Nam, an inactivated, mouse brain-derived vaccine for Japanese encephalitis (JE) has been given exclusively to ≤ 5 years old children in 3 paediatric doses since 1997. However, JE incidence remained high, especially among children aged 5-9 years. We conducted a model JE immunization programme to assess the feasibility and impact of JE vaccine administered to 1-9 year(s) children in 3 standard-dose regimen: paediatric doses for children aged <3 years and adult doses for those aged ≥ 3 years. Of the targeted children, 96.2% were immunized with ≥ 2 doses of the vaccine. Compared to the national immunization programme, JE incidence rate declined sharply in districts with the model programme (11.32 to 0.87 per 100,000 in pre-versus post-vaccination period). The rate of reduction was most significant in the 5-9 years age-group. We recommend a policy change to include 5-9 years old children in the catch-up immunization campaign and administer a 4th dose to those aged 5-9 years, who had received 3 doses of the vaccine during the first 2-3 years of life.

LAMB1 polymorphism is associated with autism symptom severity in Korean autism spectrum disorder patients.

BACKGROUND: LAMB1 encodes laminin beta-1, which is expressed during early development of the human nervous system, and could be involved in the pathogenesis of neurodevelopmental disorders. AIMS: In our study, we aimed to investigate whether single nucleotide polymorphisms (SNPs) in LAMB1 were associated with autism spectrum disorder (ASD) and with related clinical severities of ASD. METHODS: Two coding SNPs (rs20556 and rs25659) and two intronic SNPs (rs2158836 and rs2237659) were compared between 180 patients with ASD and 147 healthy control subjects using direct sequencing. The Korean version of the Childhood Autism Rating Scale (K-CARS) was used to assess clinical severities. Multiple logistic regression models were employed to analyze genetic data, and associations with symptom severity were tested with the Kruskal-Wallis and the Mann-Whitney U tests. RESULTS: None of the four examined SNPs was associated with ASD risk. However, the GG genotype of rs2158836 was associated with more severe symptoms for the "object use" and "non-verbal communication" measures. CONCLUSIONS: The results of our study suggest the association between rs2158836 polymorphisms and symptom severity in ASD.

Bodies for empire: biopolitics, reproduction, and sexual knowledge in late colonial Korea.

This paper explores the history of the biomedical construction of women's bodies as social bodies in the formation of colonial modernity in Korea. To do so, I engage with Michel Foucault's concepts of governmentality and biopolitics and the postcolonial history of medicine that has critically revisited these Foucauldian notions. These offer critical insights into the modern calculation of population and the biomedical gaze on female bodies on the Korean Peninsula under Japan's colonial rule (1910-1945). Foucauldian reflections on governmentality and colonial medicine can also shed light on the role of biomedical physicians in the advancement of colonial biopolitics. Biomedical physicians-state and non-state employees This paper explores the history of the biomedical construction of women's bodies as social bodies in the formation of colonial modernity in Korea. To do so, I engage with Michel Foucault's concepts of governmentality and biopolitics and the postcolonial history of medicine that has critically revisited these Foucauldian notions. These offer critical insights into the modern calculation of population and the biomedical gaze on female bodies on the Korean Peninsula under Japan's colonial rule (1910-1945). Foucauldian reflections on governmentality and colonial medicine can also shed light on the role of biomedical physicians in the advancement of colonial biopolitics. Biomedical physicians-state and non-state employees and colonizers and colonized alike - served as key agents investigating, knowing, and managing, as well as proliferating a discourse about, women's bodies and reproduction during Japan's empire-building. In particular, this paper sheds light on the processes by which Korean women's bodies became the objects of intense scrutiny as part of an attempt to quantify, as well as maximize, the total population in late colonial Korea. In the aftermath of the establishment of the Manchurian puppet state in 1932, Japanese imperial and colonial states actively sought to mobilize Koreans as crucial human resources for the further penetration of Japan's imperial holdings into the Chinese continent. State and non-state medical doctors meticulously interrogated, recorded, and circulated knowledge about the sexual and conjugal practices and reproductive life of Korean women in the agricultural sector, for the purposes of measuring and increasing the size, health, and vitality of the colonial population. At the heart of such medical endeavors stood the Investigative Committee for Social Hygiene in Rural Korea and Japan-trained Korean medical students/physicians, including Chóe Ug-sok, who carried out a social hygiene study in the mid-1930s. Their study illuminates the ways in which Korean women's bodies entered the modern domain of scientific knowledge at the intersection of Japan's imperialism, colonial governmentality, and biomedicine. A critical case study of the Investigative Committee's study and Chóe can set the stage for clarifying the vestiges as well as the reformulation of knowledge, ideas, institutions, and activities of colonial biopolitics in the divided Koreas.

Combination of phytochemicals, including ginsenoside and curcumin, shows a synergistic effect on the recovery of radiation-induced toxicity.

Radiotherapy is commonly used to treat solid cancers located in the pelvis. A considerable number of patients experience proctitis of varying severity, even for a considerable period after radiotherapy. These side effects are often long-lasting or progressively worsen despite multiple therapeutic efforts and are a primary cause of an unexpectedly low quality of life, even after successful cancer treatment. Therefore, this study evaluated the individual and combined efficacy of ginsenoside, curcumin, butyric acid, and sucralfate compounds in treating radiation-induced proctitis. While the candidate compounds did not affect the proliferation and migration of cancer cells, they promoted the recovery of cell activity, including motility. They exhibited anti-inflammatory effects on human dermal fibroblasts or human umbilical vein endothelial cells within in vitro disease models. When each compound was tested, curcumin and ginsenoside were the most effective in cell recovery and promoted the migration of human dermal fibroblasts and cell restoration of human umbilical vein endothelial cells. The combination of ginsenoside and curcumin resulted in cell migration recovery of approximately 54%. In addition, there was a significant improvement in the length of the endothelial tube, with an increase of approximately 25%, suggesting that the ginsenoside-curcumin-containing combination was the most effective against radiation-induced damage. Furthermore, studies evaluating the effects of combined treatments on activated macrophages indicated that the compounds effectively reduced the secretion of inflammatory cytokines, including chemokines, and alleviated radiation-induced inflammation. In conclusion, our study provides valuable insights into using curcumin and ginsenoside as potential compounds for the effective treatment of radiation-induced injuries and highlights the promising therapeutic benefits of combining these two compounds.

Reduced Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Receiving Long-Term Besifovir Therapy.

No information is available regarding the influence of besifovir (BSV), a new nucleotide analogue, on the occurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study evaluated the reduced risk of HCC in patients undergoing BSV treatment. A total of 188 patients with CHB were treated with BSV for up to 8 years. We prospectively assessed the incidence of HCC compared with the risk from prediction models. During the follow-up, 5 patients developed HCC: 1 of 139 patients with non-cirrhotic CHB, and 4 of 49 patients with liver cirrhosis. We compared the HCC incidence in non-cirrhotic and cirrhotic patients with the predicted number derived from the REACH-B (risk estimation for HCC in CHB) model and GAG-HCC (guide with age, gender, HBV DNA, core promotor mutation, and cirrhosis) model, respectively. The standardized incidence ratio (SIR) was 0.128 (p = 0.039) at 7 years in non-cirrhotic CHB patients, and the SIR was 0.371 (p = 0.047) at 7.5 years in cirrhotic patients, suggesting a significantly decreased HCC incidence in both groups. HCC prediction was available for BSV-treated patients using existing models. In conclusion, BSV decreased the risk of HCC in patients with CHB, and prediction models were applicable. Clinical trial registry website and trial number: ClinicalTrials.gov no: NCT01937806.