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Abstract Infections in early life can elicit substantially different immune responses and pathogenesis than infections in adulthood. Here, we investigate the consequences of murine cytomegalovirus infection in newborn mice on NK cells. We show that infection severely compromised NK cell maturation and functionality in newborns. This effect was not due to compromised virus control. Inflammatory responses to infection dysregulated the expression of major transcription factors governing NK cell fate, such as Eomes, resulting in impaired NK cell function. Most prominently, NK cells from perinatally infected mice have a diminished ability to produce IFN-γ due to the downregulation of long non-coding RNA Ifng-as1 expression. Moreover, the bone marrow’s capacity to efficiently generate new NK cells is reduced, explaining the prolonged negative effects of perinatal infection on NK cells. This study demonstrates that viral infections in early life can profoundly impact NK cell biology, including long-lasting impairment in NK cell functionality.

Thiabendazole (TBZ) is a benzimidazole; owing to its potent antimicrobial properties, TBZ is extensively employed in agriculture as a fungicide and pesticide. However, TBZ poses environmental risks, and excessive exposure to TBZ through various leakage pathways can cause adverse effects in humans. Therefore, a method must be developed for early and sensitive detection of TBZ over a range of concentrations, considering both human and environmental perspectives. In this study, we used silver nanopillar structures (SNPis) and Au@Ag bimetallic nanoparticles (BNPs) to fabricate a BNP@SNPi substrate. This substrate exhibited a broad reaction surface with significantly enhanced surface-enhanced Raman scattering hotspots, demonstrating excellent Raman performance, along with high reproducibility, sensitivity, and selectivity for TBZ detection. Ultimately, the BNP@SNPi substrate successfully detected TBZ across a wide concentration range in samples of tap water, drinking water, juice, and human serum, with respective limits of detection of 146.5, 245.5, 195.6, and 219.4 pM. This study highlights BNP@SNPi as a promising sensor platform for TBZ detection in diverse environments and contributes to environmental monitoring and bioanalytical studies.

Traumatic brain injury due to primary blast exposure is a major cause of ongoing neurological and psychological impairment in soldiers and civilians. Animal and human evidence suggests that low-level blast exposure is capable of inducing white matter injury and behavioural deficits. There are currently no effective therapies to treat the underlying suspected pathophysiology of low-level primary blast or concussion. Remote ischemic conditioning (RIC) has been shown to have cardiac, renal and neuro-protective effects in response to brief cycles of ischemia. Here we examined the effects of RIC in two models of blast injury. We used a model of low-level primary blast in rats to evaluate the effects of RIC neurofilament expression. We subsequently used a model of traumatic brain injury in adult zebrafish using pulsed high intensity focused ultrasound (pHIFU) to evaluate the effects of RIC on behavioural outcome and apoptosis in a post-traumatic setting. In blast exposed rats, RIC pretreatment modulated NF200 expression suggesting an innate biological buffering effect. In zebrafish, behavioural deficits and apoptosis due to pHIFU-induced brain injury were reduced following administration of serum derived from RIC rats. The results in the zebrafish model demonstrate the humoral effects of RIC independent of anesthetic effects that were observed in the rat model of injury. Our results indicate that RIC is effective in improving outcome following modeled brain trauma in pre- and post-injury paradigms. The results suggest a potential role for innate biological systems in the protection against pathophysiological processes associated with impairment following shockwave induced trauma.

Summary:. Surgical disease is now among the most common, preventable, and growing contributors to the global burden of disease. The attitudes of trainees toward global surgery and the viability of a global surgery as an academic track have blossomed. More optimized experiences within residency education are necessary, however, to prepare the next generation of global surgeons. The field of plastic surgery is thus at an important crossroads in the effort to incorporate global surgery into training programs in a uniform fashion across the country. The recent American Council of Academic Plastic Surgeons meeting in February 2020 was dedicated to identifying strategies that will enhance the adoption of global surgery practices within plastic surgery. In this article, we discuss the principles, themes, and ideas that emerged from this session, and further develop concrete initiatives believed to be potentially fruitful. Some have been discussed in other surgical disciplines or presented in isolation to the plastic surgery community, but never as a cohesive set of recommendations that take into account the background and shortfalls of the current model for global health education in the 21st century. We then introduce five recommendations to optimize learner education: (1) clarification of learner expectations and roles; (2) domestic teaching for optimization of field experiences; (3) expansion of longitudinal, formal rotations; (4) strengthening of the role of research; and (5) integration of program financing.

Natural killer (NK) cells are essential for early protection against virus infection and must metabolically adapt to the energy demands of activation. Here, we found upregulation of the metabolic adaptor hypoxia-inducible factor-1α (HIF1α) is a feature of mouse NK cells during murine cytomegalovirus (MCMV) infection in vivo. HIF1α-deficient NK cells failed to control viral load, causing increased morbidity. No defects were found in effector functions of HIF1αKO NK cells; however, their numbers were significantly reduced. Loss of HIF1α did not affect NK cell proliferation during in vivo infection and in vitro cytokine stimulation. Instead, we found that HIF1α-deficient NK cells showed increased expression of the pro-apoptotic protein Bim and glucose metabolism was impaired during cytokine stimulation in vitro. Similarly, during MCMV infection HIF1α-deficient NK cells upregulated Bim and had increased caspase activity. Thus, NK cells require HIF1α-dependent metabolic functions to repress Bim expression and sustain cell numbers for an optimal virus response.

Background : /Aims: Surgical resection or ablation is recommended for the treatment of early hepatocellular carcinoma (HCC), whereas transarterial chemoembolization (TACE) is frequently used in early HCC ineligible for curative resection. We evaluated the clinical effects and safety of radiofrequency ablation (RFA) shortly after TACE in patients with Barcelona clinic liver cancer (BCLC) stage A HCC. Methods : : Sixty-seven BCLC stage A HCC patients who failed to achieve complete response to TACE as either a first line treatment and who subsequently received RFA at the Konkuk University Medical Center from January 2005 to December 2017 were included. Evaluation indices included treatment response, overall survival rate, recurrence-free survival, prognostic factors, and procedure-related complications. Results : : Median follow-up was 46.9 months. Fifty-four (80.6%) patients were of Child-Pugh class A, and 13 (19.4%) were of class B. Modified UICC stages were I in 10 (14.9%), II in 46 (68.7%), and III in 11 (16.4%) patients. In the 67 study subjects, cumulative recurrence-free survival rates were 86.8%, 55.9% and 29.7% at 1, 3, and 5 years, respectively, and overall survival rates were 100%, 93.4%, and 83.5% at 1, 3, and 5 years, respectively. Tumor size significantly predicted recurrence. No treatment-related death occurred. Conclusion : s: Combination of RFA was an efficient and safe treatment for BCLC stage A HCC patients that failed to achieve complete response to initial TACE. We suggest TACE plus RFA be considered as a curative option for early HCC patients ineligible for curative resection of RFA.

Zebrafish are a powerful tool for investigating epilepsy. Mammalian seizures can be recapitulated molecularly, behaviorally, and electrophysiologically, using a fraction of the resources required for experiments in mammals. Larval zebrafish offer exceptionally economical and high-throughput approaches and are amenable to state-of-the-art genetic engineering techniques, providing valuable transgenic models of human diseases. For these reasons, larvae tend to be chosen for studying epilepsy, but the value of adult zebrafish may be underappreciated. Zebrafish exhibit transient larval – adult duality. The incompletely developed neural system of larval zebrafish may limit the translation of complex neurological disorders. Larval zebrafish go through dynamic changes during ontogenesis, whereas adult zebrafish are physiologically more stable. Adult zebrafish have a full range of complex brain structures and functions, such as an endothelial blood-brain barrier and adult neurogenesis, both are significant factors in epilepsy research. This review highlights the differences between larval and adult zebrafish that should be considered in pathophysiological and pharmacological studies of epilepsy.

Pollution prevention methods were applied at an optics manufacturer in an effort to improve recovery of a valuable polishing component, cerium oxide (ceria), 77% of which was lost to dragout and sewer discharge. Centrifugation and microfiltratiion were evaluated to develop a process that would increase recovery of used ceria, which would then be sent back to the ceria supplier for reclamation and reuse. Full-scale implementation included a high-speed centrifuge that operates continuously with a microfiltration system through recirculation in a single process tank. Sydor Optics has improved ceria recovery from 23% to 48%, saving thousands of dollars annually.

Solar energy has become a viable alternative energy because it is a clean type of energy that converts solar radiation into heat energy for various applications such as heating water, power generation, cooking, and food drying. The solar dryer, integrated with the heat energy storage system, uses nitrate salt as a heat storage medium which was designed and tested by drying 1000 grams of red pepper at 19.6 to 62.4°C. The average ambient temperature ranged from 19.3 to 37.4°C, and the maximum temperature of the heat storage media ranged from 87.8 to 125°C. The solar drying process was compared to open sun drying system loaded with 1000 grams of red pepper. The findings showed that the solar dryer maintained color and flavor and lowered the original moisture content from 86% to 10% for 24 hours compared to 36 hours of drying in open air. In this study, nitrate salt is shown to be the perfect heat storage medium for drying food products; it preserved heat for about 4 hours when there is no active sunlight.

Abstract In this study, we report the influences of distilled water and ammonium fluoride (NH4F) on morphology of pores in honeycomb-like titanium dioxide (TiO2) nanotube arrays. We observed the structure and arrangement of pores in the TiO2 nanotube arrays based on scanning electron microscopy images and analyzed the spatial distribution of the pores using fast Fourier transform and Voronoi diagram. We studied the individual pore properties including pore diameter, wall thickness, and interpore distance and found that locally connected ordering defects decreased with increasing distilled water concentration. Furthermore, we found that the optimum conditions of well-ordered hexagonal pore arrangement were 2 and 10 vol% distilled water with 0.2 and 0.4 wt% NH4F, respectively. Throughout this study, we provide a better understanding about the roles of distilled water and NH4F in forming well-ordered nanoscale pore structure with less ordering defects in the honeycomb-like TiO2 nanotube arrays.

Titanium dioxide (TiO2) nanoparticles were synthesized using East African highland banana (Musa AAA) and Jatropha curcas L. sap. The nanoparticles were characterized with X-ray diffractometry (XRD), Raman spectroscopy, Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). FT-IR peaks show presence of amino, carboxyl and hydroxyl groups on the crystal surface of the nanoparticles. XRD and Raman characteristic indicate anatase phases. The average crystallite size calculated from XRD peak width using Scherrer equation are 5.5 nm and 6.1 nm for Jatropha and Musa AAA sap TiO2 particles respectively. SEM images show polydispersed spherical clusters of agglomerated nanoparticles. The nanoparticles showed antimicrobial activity against gram-negative bacteria when irradiated in natural sunlight for 2 h. The sap extracts provide a simple, cheaper and more environmentally benign reducing and stabilizing agents for transforming transition metal salts into nano-scale particles, which have wide range of industrial applications. Keywords: Biosynthesis, Fourier transform infrared, Musa AAA, Raman spectroscopy, TiO2 nanoparticles, X-ray diffraction

Innate lymphoid cells (ILCs) were originally classified based on their cytokine profiles, placing natural killer (NK) cells and ILC1s together, but recent studies support their separation into different lineages at steady-state. However, tumors may induce NK cell conversion into ILC1-like cells that are limited to the tumor microenvironment and whether this conversion occurs beyond this environment remains unknown. Here, we describe Toxoplasma gondii infection converts NK cells into ILC1-like cells that are distinct from both steady-state NK cells and ILC1s in uninfected mice. These cells were Eomes-dependent, indicating that NK cells can give rise to Eomes– Tbet-dependent ILC1-like cells that circulate widely and persist independent of ongoing infection. Moreover, these changes appear permanent, as supported by epigenetic analyses. Thus, these studies markedly expand current concepts of NK cells, ILCs, and their potential conversion.

Background:. Although efforts to improve access to care for patients with cleft lip in the developing world have grown tremendously, there is a dearth of data regarding aesthetic outcomes after cleft lip repairs in this setting. Defining severity-outcome relationships has the potential to improve efficiency of care delivery in resource-limited settings, and to improve overall results. In this study, we investigate the relationship between initial cleft lip severity and early aesthetic outcomes following surgical repair of primary unilateral cleft lip. Methods:. Using previously validated tools to assess unilateral cleft lip severity and aesthetic outcome after repair, we evaluated 1,823 consecutive patients who underwent primary unilateral cleft lip/nose (UCL/N) repair. Three separate evaluators scored each case for a total of 5,469 total independent evaluations. Results:. Our results show that with increasing severity of UCL/N deformity, there is a corresponding decrease in early aesthetic outcome scores. Using our results, we established normative early aesthetic outcomes following repair for each severity grade of UCL/N deformity. Conclusions:. In conclusion, this study has achieved a standardized, timely, and cost-effective evaluation of 1,823 surgical cases of primary UCL/N repair. This data set provides a normal distribution of aesthetic results according to initial cleft severity and defines a standard of “expected” aesthetic results after primary UCL/N repair. Our results also show a clear correlation between initial severity and immediate aesthetic result after surgery, though we also show that excellent results are possible regardless of initial cleft severity.

Targeted therapies designed to exploit specific molecular pathways in aggressive cancers are an exciting area of current research. Mixed Lineage Leukemia (MLL) mutations such as the t(4;11) translocation cause aggressive leukemias that are refractory to conventional treatment. The t(4;11) translocation produces an MLL/AF4 fusion protein that activates key target genes through both epigenetic and transcriptional elongation mechanisms. In this study, we show that t(4;11) patient cells express high levels of BCL-2 and are highly sensitive to treatment with the BCL-2-specific BH3 mimetic ABT-199. We demonstrate that MLL/AF4 specifically upregulates the BCL-2 gene but not other BCL-2 family members via DOT1L-mediated H3K79me2/3. We use this information to show that a t(4;11) cell line is sensitive to a combination of ABT-199 and DOT1L inhibitors. In addition, ABT-199 synergizes with standard induction-type therapy in a xenotransplant model, advocating for the introduction of ABT-199 into therapeutic regimens for MLL-rearranged leukemias.

Study DesignRetrospective clinical study.PurposeTo assess the diagnostic value of suction drain tip culture in patients undergoing primary posterior spine surgery.Overview of LiteratureTo date, the diagnostic value of suction drain tip culture for predicting surgical site infection (SSI) has not been firmly established in orthopedic or spinal surgery.MethodsIn total, 133 patients who underwent primary posterior spine surgery from January 2013 to April 2015 were included in this retrospective study. Patients diagnosed with infective disease or condition was excluded. The suction drain tip was cut off approximately 5 cm from its far end. The sample was sent to the microbiological laboratory of the hospital for culture analysis. Any signs of infection, such as wound discharge or dehiscence, fever, chills, or chronic pain, were recorded. The culture outcome, identification of bacteria, and postoperative transition of the serum C-reactive protein level were also recorded in all patients. The wounds were followed up for a minimum of 3 months.ResultsA positive drain tip culture was found in 48 patients (36.1%), of whom, 6 developed SSI. The sensitivity of drain tip culture for SSI after primary posterior spine surgery was 60.0%, and the specificity was 65.9%. The association between the incidence of positive suction tip culture and SSI was not statistically significant. Among the 48 positive drain tip cultures, there was no significant association between the occurrence of SSI and virulence of isolated bacteria. There was no significant association between drain tip culture positivity and the duration of drainage, or between the rate of SSI and duration of drainage.ConclusionsSuction drain tip culture analysis is a poor predictor of SSI after primary posterior spine surgery. Routine use of a drain tip culture is not supported by the results of this study.

Summary:. Neuromas can be a debilitating cause of pain and often negatively affect patients’ quality of life. One effective method of treatment involves surgical resection of the painful neuroma and use of a processed nerve allograft to repair the injured nerve segment. Giving the nerve “somewhere to go and something to do” has been shown to effectively alleviate pain in upper and lower extremities. We present the first report of this concept to treat a painful neuroma of the abdominal wall that developed following a laparoscopic gastric bypass. The neuroma was excised, and the affected nerve was reconstructed using a processed nerve allograft as an interposition graft, with resolution of pain and gradual return of normal sensation. Patient-reported outcomes were measured using the Patient Reported Outcomes Measurement Information System. Neuroma excision with concurrent interposition grafting using processed nerve allografts may be a promising method of treatment for postsurgical painful neuromas of the trunk.

There is strong evidence that primary blast injuries can cause neuropathological alterations in the brain. Clinical findings from war veterans indicating evidence of diffuse axonal injury have been corroborated by numerous primary blast models in animals. However, the effect of a subclinical blast (blast with no obvious sign of external trauma or lung injury) as a contributing factor to the neurological symptoms and neuropathology is less clear. Our group recently developed a model of low-level primary blast and characterized aberrant expression of white matter cytoskeletal proteins in the cortex and hippocampus following a subclinical wave shock exposure. Here we examined the susceptibility of the corpus callosum following subclinical blast. We also demonstrate that white matter dysfunction is associated with neurobehavioral deficits associated with anxiety and stress in rats. Anesthetized male Sprague–Dawley rats (~300 g) were exposed to a primary blast (approx. 28 kPa), below the threshold required to induce pulmonary trauma. Rats were evaluated on three behavioral outcome measures; the rotarod, the light/dark box and open field anxiety test. We used Western blotting to examine expression and degradation of axonally expressed αII-spectrin, NF200 and voltage-gated sodium channels (VGSC) in the corpus callosum. Acute slice preparations were used for electrophysiological analysis of evoked compound action potentials (CAPs) in the corpus callosum. There was evidence of αII-spectrin degradation in the corpus callosum at 48 h post-injury detectable up to 14 days post-injury, as well as increased heavy neurofilament expression. A reduction in VGSC expression was observed at 48 h post-blast as well as a reduction in the interaction between ankyrin G and intact αII-spectrin. Blast exposed rats had significantly lower rotarod latency times relative to sham rats (p=0.002). Increased anxiety-related and stress-related behavior were observed in blast rats relative to sham animals as indicated by the increased frequency of fecal droppings (p=0.029) and reduced exploratory activity (p=0.036) in the open-field test. Blast rats had fewer transitions and time spent in lit sections of the light/dark box. Electrophysiological recordings from the corpus callosum indicated greater deficits in unmyelinated fibers of the corpus callosum relative to myelinated fibers characterized by reduced CAP amplitude response at 14 days post-injury. Analysis of the relationship between stimulation distance to evoked response indicated an underlying abnormality in N1 myelinated fibers at close stimulation distances. Collectively, our results indicate that subclinical blast exposure can result in persistent neurological changes in cerebral white matter occurring in parallel with detectable neurobehavioral deficits.

Immunoglobulin A (IgA) nephropathy associated with cirrhosis is the most common form of secondary IgA nephropathy (IgAN). Cirrhosis-related IgAN is usually clinically silent with a rare occurrence of gross hematuria, unlike in cases of idiopathic IgAN. Especially, acute tubular necrosis (ATN) associated with gross hematuria is very rare in cirrhosis-related IgAN, although acute renal failure is a frequently reported complication in advanced cirrhosis. Herein, we report an unusual case of ATN requiring renal replacement therapy, associated with gross hematuria in a patient with nonalcoholic, hepatitis B virus-associated cirrhosis. Results of a histopathological analysis revealed obstruction of the lumen of renal tubules by red blood cell casts, a marked tubular necrosis, and IgA deposition in the mesangium. The patient's renal function and gross hematuria were clearly improved after lamivudine treatment.

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