Aberrant SOX10 and RET expressions in patients with Hirschsprung disease.

BACKGROUND: HSCR is a complex genetic disorder characterized by the absence of ganglion cells in the intestine, leading to a functional obstruction. It is due to a disruption of complex signaling pathways within the gene regulatory network (GRN) during the development of the enteric nervous system (ENS), including SRY-Box Transcription Factor 10 (SOX10) and REarranged during Transfection (RET). This study evaluated the expressions of SOX10 and RET in HSCR patients in Indonesia. METHODS: Total RNA of 19 HSCR ganglionic and aganglionic colons and 16 control colons were analyzed using quantitative real-time polymerase chain reaction for SOX10 and RET with GAPDH as the reference gene. Livak's method (2-ΔΔCT) was used to determine the expression levels of SOX10 and RET. RESULTS: Most patients were males (68.4%), in the short aganglionosis segment (78.9%), and had undergone transanal endorectal pull-through (36.6%). There were significant upregulated SOX10 expressions in both ganglionic (2.84-fold) and aganglionic (3.72-fold) colon of HSCR patients compared to controls' colon (ΔCT 5.21 ± 2.04 vs. 6.71 ± 1.90; p = 0.032; and ΔCT 4.82 ± 1.59 vs. 6.71 ± 1.90; p = 0.003; respectively). Interestingly, the RET expressions were significantly downregulated in both ganglionic (11.71-fold) and aganglionic (29.96-fold) colon of HSCR patients compared to controls' colon (ΔCT 12.54 ± 2.21 vs. 8.99 ± 3.13; p = 0.0004; and ΔCT 13.90 ± 2.64 vs. 8.99 ± 3.13; p = 0.0001; respectively). CONCLUSIONS: Our study shows aberrant SOX10 and RET expressions in HSCR patients, implying the critical role of SOX10 and RET in the pathogenesis of HSCR, particularly in the Indonesian population. Our study further confirms the involvement of SOX10-RET within the GNR during the ENS development.

The role of focused assessment sonography for trauma (FAST) on the outcomes in patients with blunt abdominal trauma following non-operative therapy: A cohort study.

Background: The non-operative management of blunt abdominal trauma had a high success rate and is expected to reduce the length of hospitalization and patients' morbidity. Here, we aim to evaluate the outcomes of patients with blunt abdominal trauma after non-operative management and associate them with prognostic factors. Methods: We performed a retrospective analysis on patients with blunt abdominal trauma who received non-operative management (NOM) at our institution from April 2018 to April 2021. Results: Two hundred eleven patients were included in this study who underwent non-operative management. Most of the subjects (73%) were males, with male to female ratio of 2.7:1. Most patients aged 20-29 years old (29.4%), FAST negative (62.1%), minor injured (45%), successfully managed nonoperatively (98.6%), received no transfusion (38.9%), and injured due to traffic accident (80.1%). ISS was significantly associated with FAST (p = 0.028), while male gender, NLR, PLR, and blood transfusion did not (p > 0.05). The presence of external injury was associated with FAST results (p = 0.039), while the head, facial, thoracic, pelvic, and skeletal injuries did not (p > 0.05). We also found a significant correlation between blood transfusion and patient survival with NOM outcomes (p = 0.047 and p = 0.041, respectively). Furthermore, external injury significantly correlated with NOM outcomes (p = 0.042). Multivariate analysis showed that external and pelvic injury was significantly associated with NOM outcomes (p < 0.0001 and p = 0.036, respectively). Conclusions: The results of the FAST examination were not associated with the outcome of non-operative therapy. Moreover, the successful outcome of NOM might be affected by blood transfusions, the presence of external injuries, and pelvic injury.

The effect of NPWT in wound healing and bacterial count on deep dermal burn injury model: An experimental study.

Background: Sepsis is one of the main causes in burn victim's mortality. The use of negative pressure wound therapy (NPWT) provides an ideal environment to accelerate wound healing. We compare the use of normal saline (NS), intermittent NPWT, continuous NPWT and silver sulfadiazine in wound healing process. Method: This study involved 6 Yorkshire pigs; each pig was induced with 20 burns on the flank area. Burns were divided into 4 treatment groups: NS gauze, intermittent NPWT, continuous NPWT, and silver sulfadiazine dressing. Burns were evaluated on day 1,3,7,14, and 21 for its morphology and bacterial colonization and on day 14 and 21 for the remaining burn surface area. Result: Wound that received NPWT therapy appeared better in both granulation and crust formation. Remaining burn surface area (mm2) on day 14 in NS group, intermittent NPWT, continuous NPWT, and silver sulfadiazine were 107.43 ± 83.43, 178.07 ± 74.83, 146.10 ± 69.1, 126.03 ± 83.22, respectively(p = 0.457); on day 21 in NS group, intermittent NPWT, continuous NPWT, and silver sulfadiazine were 13.16 ± 16.86, 59.49 ± 20.72, 54.79 ± 46.59, 48.95 ± 39.84, respectively(p=0.169). There were no significant differences in each treatment group bacterial colonization(p>0.05). There were no significant correlation between bacterial colonization and remaining burn surface area (p>0.05). Conclusion: While morphologically, the wound in NPWT treatment groups appeared better in granulation and crust formation, the remaining wound surface area and the number of bacterial colonization were not significantly difference compared to standard therapy (silver sulfadiazine and NS gauze). There were no significant correlation between the amount of bacterial colonization and remaining wound surface area on every treatment group.

Controlling environmental pollution: dynamic role of fiscal decentralization in CO2 emission in Asian economies.

The "environment" has become one of the important and debatable topics of the world and policymakers identifying the new predictors of CO2 emissions. Therefore, some economies have been promoting fiscal decentralization to encourage environmental quality by granting more financial autonomy to provincial and sub-national governments. Therefore, this study evaluates the dynamic effect of fiscal decentralization on CO2 in selected nine Asian economies using a fresh dynamic panel ARDL model from 1984 to 2017. The empirical findings show that fiscal decentralization has asymmetric effects on CO2 emissions because a positive change in revenue and expenditure decentralization reduced CO2 emissions in Asia. Moreover, a negative change in expenditure decentralization has also enhanced CO2 emissions in the long run. Thus, clean environmental policies and recommendations can be revised and proposed based on nonlinear findings in the modern era.

The COVID-19 pandemic impact on pediatric surgery residency programs.

BACKGROUND: The residency program as a part of the clinical services itself has been influenced by the COVID-19 outbreak. Several reports have been published regarding the impact of COVID-19 on the residency programs; however, all studies were performed in developed countries or did not comprehensively analyze what residents think about the COVID-19 impact on their residency program. We investigated the impact of the COVID-19 pandemic on the pediatric surgery residency program in our institution as an important part of hospital medical services. METHODS: We developed and distributed a questionnaire to pediatric surgery residents in our institution who were registered from January 2015-July 2020. The questionnaire was consisting of 24 questions: a) the perspectives of residents about COVID-19 infection during their residency program; b) the learning process; c) academic evaluations; and d) residents' suggestions to improve the quality of their residency program during the outbreak. RESULTS: Most (82.6%) pediatric surgery residents agreed that elective surgeries should be postponed during the pandemic. Before the outbreak, almost all (82.6%) residents used textbooks and journals as their primary sources of learning, while during the outbreak, 69.5% of residents shifted to use online lectures either from the school or Association of Pediatric Surgeons. Interestingly, 91.3% of participants agreed that they had more time to complete their academic assignments during the pandemic. CONCLUSIONS: The pandemic has had a significant impact on the development of pediatric surgery residency programs. Moreover, the responses to the questionnaire are affected by the seniority and sex of the residents. A comprehensive approach is needed to maintain the high standard of competence of pediatric surgery without compromising our safety from the COVID-19 infection risk.

Global policy responses to the COVID-19 pandemic: proportionate adaptation and policy experimentation: a study of country policy response variation to the COVID-19 pandemic.

Background: Concern for the development of actions against COVID-19 has continued to grow since February 2020. Government responses remain a crucial part of preventing virus transmission through policy formulation and strengthening national capacity. Methods: This study has used quantitative analysis, using secondary data from 177 countries. The variables consist of Global Health Security (GHS) category and COVID-19 pandemic. An analysis of the appropriateness of the government's policy response in dealing with the COVID-19 pandemic was carried out by comparing the two variables. Results: The study indicated a significant relationship between global health security category and pandemic score (P < 0.01). There were 37 countries out of 177 (20.9%) categorized as under-reaction and least-reaction. Conclusion: Pandemic COVID-19 score, rated based on doubling time, is directly significant with the health security category. The government should improve its responsiveness and preparation to improve national capacity during the novel coronavirus pandemic.

Optimizing Steam Consumption of Mushroom Canning Process by Selecting Higher Temperatures and Shorter Time of Retorting.

Increasing energy cost has driven the food canning industries to optimize their energy consumption in order to produce safe and shelf-stable foods efficiently. In the mushroom canning industry, energy efficiency is very critical to improve product (price) competitiveness. This research aimed at demonstrating total steam consumption to achieve the same sterility level (F 0-value) of canned mushroom by using different combinations of times and temperatures of retorting. Agaricus bisporus in brine contained in 300 × 407 cans was heat processed in a horizontal static retort. Three different retort temperatures (115, 121, and 130°C) and different operator processing times ranging from 2 to 97 minutes were employed to achieve different levels of F 0-values. Our results showed that at the same level of sterility, steam consumption inversely decreased with the increase of retort temperature. At the same F 0-value of 10 minutes, energy efficiency for up to 72.9% and 58.1% per batch of retorting was achieved by increasing the temperature from 115 to 130°C and 115 to 121°C, respectively. Since steam consumption is a major element of production costs in the canning industry, the selection of higher temperatures and shorter time of retorting will have a positive commercial impact due to the reduction of production costs.

Comparison of metamizole and paracetamol effects on colonic anastomosis and fibroblast activities in Wistar rats.

BACKGROUND: Leakage following colorectal anastomosis surgery causes various complications associated with high morbidity and mortality, especially in pediatric patients. It might be caused by the use of non-steroidal anti-inflammatory drugs (NSAIDs) as postoperative analgesics. This study aimed to compare the effect of metamizole and paracetamol on colonic anastomosis and fibroblast activities, including proliferation, migration, and collagen synthesis, in Wistar rats. METHODS: Rats were divided into control, paracetamol and metamizole groups. The colonic anastomosis was evaluated by determining the integrity of the muscle layers, the formation of granulation tissue, and mucosal anastomosis. Fibroblast activities were analyzed by measuring the proliferation, migration, and collagen synthesis. RESULTS: Metamizole caused more damage to muscle layer integrity, more inhibition of granulation tissue formation in the anastomosis area and lower mucosal anastomosis compared with paracetamol and control groups. Metamizole had a higher cytotoxic effect than paracetamol, which suppressed the proliferation and migration of fibroblasts. Furthermore, both drugs did not affect the synthesis of collagen. CONCLUSION: Metamizole shows worse effects on the integrity of muscle layers, inhibition of granulation tissue formation, mucosal anastomosis, fibroblast proliferation, and migration, but not collagen synthesis, than paracetamol in Wistar rat intestines following colonic anastomosis. These findings might indicate that paracetamol is safer than metamizole as analgesic following colonic anastomosis.

Equivalence Test between the Physicochemical Properties of Transgenic and Non-Transgenic Soy Flour.

Soybeans are a source of plant-based protein with a fairly complete composition of essential amino acids. Most of the soybean raw material in Indonesia originates from the United States of America where around 75% of the soybeans are transgenic soybeans (Roundup Ready GMO). One of the easily produced and practical soybean products is soy flour. The purpose of this study was to compare the physicochemical properties of flour made from three types of soybeans: local soybeans, imported transgenic soybeans, and imported non-transgenic soybeans. The study was conducted in two phases: the preliminary study, where the physicochemical properties of the three varieties of soybeans were assessed, and the main study which involved the production of soy flour and the analysis of their physicochemical properties. The results of the preliminary analysis revealed that the local soybeans had greater length and width dimensions, volume, bulk density, 100-seed weight, and protein content than transgenic and imported non-transgenic soybeans. The statistical analysis demonstrated that soybean variety had a significant effect on the physicochemical properties of the flour produced, namely the yield, color, water activity, bulk density, repose angle, moisture, ash, protein, fat, and mineral content, and the antioxidant capacity parameters. On the other hand, soybean variety did not have a significant effect on the carbohydrate and total phenolic content. Based on the physicochemical properties, local soy flour had a number of properties that were equivalent to those of imported soy flour and was even superior in its protein content and antioxidant capacity.

Aberrant UBR4 expressions in Hirschsprung disease patients.

BACKGROUND: Recently, pathogenic alleles within ubiquitin N-recognin domain-containing E3 ligase 4 (UBR4) gene have been shown to be associated with Hirschsprung disease (HSCR). We determined the UBR4 expressions in Indonesian HSCR patients. METHODS: We analyzed the UBR4 expressions in the colons of HSCR patient and anorectal malformation (ARM) patient as control by real-time polymerase chain reaction (qPCR). RESULTS: Thirty-seven patients with non-syndromic HSCR and eighteen controls were involved in this study. qPCR revealed that the UBR4 expression was strongly decreased (0.77-fold) in the ganglionic group of patients with HSCR compared to the control group with ARM (ΔCT 2.43 ± 0.36 vs. 2.05 ± 0.69; p = 0.009), whereas the UBR4 expression was also significantly reduced (0.79-fold) in the aganglionic group of patients with HSCR compared to the control group with ARM (ΔCT 2.39 ± 0.46 vs. 2.05 ± 0.69; p = 0.044). However, the UBR4 expression change was not associated with gender (p = 0.35 and 0.80), nor with degree of aganglionosis both in ganglionic and aganglionic colons (p = 0.72 and 0.73), respectively. CONCLUSION: Our study demonstrates that expression of UBR4 is decreased in both aganglionic and ganglionic colon of HSCR patients.

Why does network governance fail in managing post-disaster conditions in the Philippines?

Disasters are the litmus test of governance. The inherent complexity of disasters places government agencies and societies in vulnerable situations. This study uses the mixed-method approach to social network analysis in evaluating the network structure of the Philippine disaster management and its implications for disaster governance. A survey was conducted among the target 56 identified disaster response-related agencies and organisations from the disaster management networks of the most susceptible areas in the Philippines - Cities of Cagayan de Oro and Iligan, Province of Misamis Oriental and the overall Region 10 disaster response network, aimed at measuring the existing relationships among member agencies. Forty-four agencies and organisations were able to participate in the survey. Also, key informant interviews were conducted among the representatives of the lead agencies, non-government organisations and survivors of Typhoon Washi. The findings revealed that the mandated tall structure and the lead organisation form of network governance as stipulated in Republic Act 10121 does not work in the regional and local disaster management networks in Region 10, particularly during Typhoon Washi in 2010. At the regional level, such structure does not build interdependencies among agencies, while at the local level, disaster response operations are constrained by bureaucratic protocols making disaster management networks ineffective. At the regional level, where many agencies and organisations are involved, the existing less centralised structure of decision-making should be transformed into a highly centralised structure, while disaster operations should be improved through coordination at all levels of disaster operations and intensified collaboration with non-government agencies.

Effect of tocopherols, tocotrienols, ß-carotene, and chlorophyll on the photo-oxidative stability of red palm oil.

Effect of tocols, ß-carotene, and chlorophyll on photo-oxidative stability of red palm oil (RPO) were studied. Model systems of triacylglycerols+tocols, triacylglycerols+ß-carotene, triacylglycerols +tocols+ß-carotene, and triacylglycerols+tocols+ß-carotene+chlorophyll were exposed to fluorescent light at intensities of 5,000, 10,000, and 15,000 lux for 7 h at 30±2°C. Changes in concentrations of tocopherols, tocotrienols, ß-carotene, chlorophyll, and peroxide values were evaluated every hour. Light intensity accelerated degradation of tocols in the triacylglycerols+tocols system and ß-carotene in the triacylglycerols+ß-carotene system. Gamma-tocotrienol showed the highest degradation rate and ß-carotene was the most sensitive compound to changes in light intensity, indicated by the lowest light intensity coefficient (zi) value. The presence of tocols and ß-carotene together showed protective effects for the photo-oxidative stability of RPO. The presence of chlorophyll increased the rate of photo-oxidation at high light intensities. Interactions between tocols and ß-carotene contributed to the photo-oxidative stability of RPO.

Chronic hyperaldosteronism in cryptochrome-null mice induces high-salt- and blood pressure-independent kidney damage in mice.

Although aldosterone has an essential role in controlling electrolyte and body fluid homeostasis, aldosterone also exerts certain pathological effects on the kidney. Several previous studies have attempted to examine these deleterious effects. However, the majority of these studies were performed using various injury models, including high-salt treatment and/or mineralocorticoid administration, by which the kidney changes observed were not only due to aldosterone but also due to prior injury caused by salt and hypertension. In the present study, we investigated aldosterone's pathological effect on the kidney using a mouse model with a high level of endogenous aldosterone. We used cryptochrome-null (Cry 1, 2 DKO) mice characterized by high aldosterone levels and low plasma renin activity and observed that even under normal salt exposure conditions, these mice showed increased albumin excretion and kidney tubular injury, decreased nephrin expression and increased reactive oxygen species production in the absence of hypertension. Exposure to high salt levels exacerbated the kidney damage observed in these mice. Moreover, we noted that decreasing blood pressure without blocking aldosterone action did not provide beneficial effects to the kidney in high-salt-treated Cry 1, 2 DKO mice. Thus, our findings support the hypothesis that aldosterone has deleterious effects on the kidney independent of high-salt exposure and high blood pressure.

Glycosaminoglycan overproduction in the aorta increases aortic calcification in murine chronic kidney disease.

BACKGROUND: Vascular calcification accompanying chronic kidney disease increases the mortality and morbidity associated with cardiovascular disorders, but no effective therapy is available. We hypothesized that glycosaminoglycans may contribute to osteoblastic differentiation of vascular smooth muscle cells during vascular calcification. METHODS AND RESULTS: We used exostosin-like glycosyltranferase 2-deficient (EXTL2 knockout) mice expressing high levels of glycosaminoglycans in several organs including the aorta. We performed 5/6 subtotal nephrectomy and fed the mice a high-phosphate diet to induce chronic kidney disease. Overexpression of glycosaminoglycans in the aorta enhanced aortic calcification in chronic kidney disease in EXTL2 knockout mice. Ex vivo and in vitro, matrix mineralization in aortic rings and vascular smooth muscle cells of EXTL2 knockout mice was augmented. Furthermore, removal of glycosaminoglycans in EXTL2 knockout and wild-type mice-derived vascular smooth muscle cells effectively suppressed calcium deposition in a high-phosphate environment. CONCLUSIONS: These results illustrate an important role for glycosaminoglycans in the development of vascular calcification. Manipulation of glycosaminoglycan expression may have beneficial effects on the progression of vascular calcification in chronic kidney disease patients.

Aging in dense suspensions of soft thermosensitive microgel particles studied with particle-tracking microrheology.

Using particle tracking microrheology, we studied the glass transition in dense suspensions of thermosensitive microgel particles. These suspensions can be tuned reversibly between the glass state at low temperature and the liquid state at high temperature. In the glass state, the ensemble averaged mean squared displacements (MSDs) of added fluorescent tracer particles depend on the age of the suspension. We also determine the local viscoelastic moduli, G' and G", from the MSDs using the Generalized Stokes-Einstein Relation and compare them to the bulk moduli, measured using conventional rheometry. With particle tracking, one probes the viscoelastic moduli in a lower frequency range than with macrorheology, which makes it possible to determine the mean relaxation time that is inaccessible with macrorheology. In the glass state, the mean relaxation time increases linearly with the age of the sample and the short time particle displacement distributions are non-Gaussian, indicating inhomogeneity of the system. The observed difference between conventional and microrheology is explained quantitatively assuming that the tracer particles are surrounded by a viscoelastic liquid shell, different from the bulk.

Glass transition and aging in dense suspensions of thermosensitive microgel particles.

We report a thermosensitive microgel suspension that can be tuned reversibly between the glass state at low temperature and the liquid state at high temperature. Unlike hard spheres, we find that the glass transition for these suspensions is governed by both the volume fraction and the softness of the particles, where softer suspensions form a glass at higher effective volume fractions. In the glass state, these suspensions show aging where the relaxation times increase linearly with age, irrespective of the degree of particle softness. This relaxation scaling is in contrast with hard sphere behavior but consistent with the soft glassy rheology model.

Rheological properties of aging thermosensitive suspensions.

Aging observed in soft glassy materials inherently affects the rheological properties of these systems and has been described by the soft glassy rheology (SGR) model [S. M. Fielding, J. Rheol. 44, 323 (2000)]. In this paper, we report the measured linear rheological behavior of thermosensitive microgel suspensions and compare it quantitatively with the predictions of the SGR model. The dynamic moduli [G'(omega,t) and G''(omega,t)] obtained from oscillatory measurements are in good agreement with the model. The model also predicts quantitatively the creep compliance J(t - t(w),t(w)), obtained from step stress experiments, for the short time regime [(t - t(w)) < t(w)]. The relative effective temperature X/X(g) obtained from both the oscillatory and the step stress experiments is indeed less than 1 (XX(g) < 1) in agreement with the definition of aging. Moreover, the elasticity of the compressed particles (G(p)) increases with increased compression, i.e., the degree of hindrance and consequently also the bulk elasticity (G' and 1/J) increases with the degree of compression.