Microbe-mediated intestinal NOD2 stimulation improves linear growth of undernourished infant mice.

The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain LpWJL) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that LpWJL sustains the postnatal growth of malnourished conventional animals and supports both insulin-like growth factor-1 (IGF-1) and insulin production and activity. We have identified cell walls isolated from LpWJL, as well as muramyl dipeptide and mifamurtide, as sufficient cues to stimulate animal growth despite undernutrition. Further, we found that NOD2 is necessary in intestinal epithelial cells for LpWJL-mediated IGF-1 production and for postnatal growth promotion in malnourished conventional animals. These findings indicate that, coupled with renutrition, bacteria cell walls or purified NOD2 ligands have the potential to alleviate stunting.

Mechanical Characterization and Standardization of Silicon Scalp and Dura Surrogates for Neurosurgical Simulation.

BACKGROUND: Simulation-based neurosurgical training allows the development of surgical skills outside the operating room. However, the use of nonstandardized materials and poor haptic feedback remain the primary limitations of the surgical simulators. Therefore, this work proposes a comprehensive scheme for scalp and dura surrogate synthesis and their standardization for neurosurgical training. METHODS: Eight different variants of silicone-based scalp (S1-S8) and dura (D1-D8) surrogates were synthesized. The samples were evaluated by 26 neurosurgeons. They provided their feedback in a Likert scale questionnaire. Kruskal-Wallis test with Dunn multiple comparisons was used for statistical analysis of surgeons' scores. The samples were mechanically characterized using Shore A hardness and dynamic nanoindentation testing. RESULTS: The highest mean Likert score values were obtained for S3 scalp and D8 dura variants. The comparison of S3 and D8 with the rest of the variants in the respective groups was statistically significant in 21 of 28 instances. The average Shore A hardness and storage modulus of the S3 variant were 21.9 DU and 505.3 kPa, respectively. The corresponding values for the D8 variant were 32.5 DU and 632 kPa, respectively. CONCLUSIONS: This study proposes a method for the synthesis, evaluation, and standardization of scalp and dura surrogates. The study achieved standardized silicone compositions along with a recommendable range of Shore hardness and viscoelastic moduli values for the scalp and dura surrogates. This work can be extended for the standardization of surrogates for other tissues involved in neurosurgical simulators.

Evaluation of the Efficacy of Intralesional Measles, Mumps, and Rubella Vaccine with Intralesional Vitamin D3 as Immunotherapies in the Treatment of Recalcitrant Cutaneous Warts in Adult- A Randomized Placebo-Controlled Study.

INTRODUCTION: Currently, various destructive and ablative treatment options are conventionally used for warts, but all of them are limited in some form by their adverse effects, high recurrences, suboptimal effectiveness, and the need to treat every wart. Lately, immunotherapy has emerged as a safe treatment relying on biological substances that modulate the immune system to achieve disease control. AIMS AND OBJECTIVES: We aimed at conducting a placebo-controlled study to compare the rate of efficacy of intralesional MMR vaccine with vitamin D3 in the management of recalcitrant extragenital warts in immune-competent adults. Follow-up was done at third and sixth month. MATERIALS AND METHODS: Patients were divided into three groups, namely, group A, B, and C. Groups A, B, and C received intralesional MMR vaccine, vitamin D3 and normal saline, respectively, in the largest wart. The injections were repeated every 2 weeks, for a maximum of four injections. RESULTS: Among injected warts, in group A, complete clearance was seen in 29 (87.8%) patients, partial clearance in two (6.1%) and no response in two (6.1%) patients. In group B, 24 (77.4%) patients, five (16.1%) patients, and two (6.5%) patients showed signs of complete, partial, and no clearance, respectively, in injected warts. Complete response in distant warts was seen in 25 (75.7%) patients in group A and 20 (64.5%) patients in group B. There was no statistically significant difference between responses of the two groups. In group C, only three (12.5%) patients had complete clearance in injected warts, and none in distant warts. Recurrence was seen in two (6.4%) patients, each in group B and C. However, for management of verruca plana MMR was found to be superior to vitamin D3. LIMITATIONS: Our study was limited by a small sample size, absence of immunological analysis, and limited follow-up period. CONCLUSION: MMR vaccine and vitamin D3 are equally effective and safe treatment option for multiple, recalcitrant warts, as well as warts on difficult to treat sites with minimal recurrence.

A Poly-vinyl Alcohol (PVA)-based phantom and training tool for use in simulated Transrectal Ultrasound (TRUS) guided prostate needle biopsy procedures.

Trans-rectal ultrasound-guided needle biopsy is a well-established diagnosis technique for prostate cancer. To enhance the needle manoeuvring skills under ultrasound (US) guidance, it is preferable to train medical practitioners in needle biopsy on tissue-mimicking phantoms. This phantom should mimic the morphology as well as mechanical and acoustic properties of the human male pelvic region to provide a surgical experience and feedback. In this study, polyvinyl alcohol (PVA) was used and evaluated for prostate phantom development, that is stiffness tunable, US-compatible and durable phantom material. Three samples, each with 5%, 10%, and 15% concentration of PVA material, were prepared, and their mechanical and shrinkage characteristics were investigated. The anatomy of male pelvic region was used to develop an anatomically correct phantom. Later US-guided needle biopsy was performed on the phantom. The range of elastic moduli of the PVA samples was 2∼146 kPa. Their elastic moduli and volumes were found to remain statistically close from seventh to eighth freeze-thaw cycle (p>0.05). Initial US scans of the phantom resulted in satisfactory B-mode images, with a clear distinction between the prostate and its surrounding organs. This study demonstrated the applicability of PVA hydrogel as a phantom material for training in US-guided needle biopsy.

Estimating the Impact of Extragenital Warts versus Genital Warts on Quality of Life in Immunocompetent Indian Adult Patients: A Comparative Cross-Sectional Study.

BACKGROUND: Extra-genital warts (EGWs) affect 7-10% of population. Even though a plethora of studies have been conducted to assess the impact of genital warts (GWs) showing a significant impact on the quality of life but surprisingly, barely any data has been collected on the impact of EGWs on quality of life. AIMS AND OBJECTIVE: This cross-sectional study aimed at comparing the magnitude of EGWs on health-related quality of life and various variables with that of GWs. PATIENTS AND METHODS: The study consisted of two groups of immunocompetent adults, each with 100 patients aged 18 years or above, attending the skin outpatient department at our tertiary center between April 2018 and March 2019 and consented to participate. Group A consisted of patients with EGWs and group B comprised of patients with GWs. All patients were asked to fulfill the validated Hindi hard copy of the Dermatology Life Quality Index (DLQI) questionnaire. RESULTS: The mean DLQI score of patients with EGWs was 8.73 ± 0.84 and that of patients with GWs was 5.83 ± 0.83 (P = 0.026). In group A, those affected the most were patients with warts on multiple exposed sites (mean DLQI score of 14), followed by warts on feet (mean DLQI score of 10.69), followed by warts on hands (DLQI score of 9.12), and facial warts (DLQI score of 6.80). Patients with a prior history of failed treatment and/or a longer duration of illness had a higher level of dissatisfaction. To the best of our knowledge, no such study has been conducted in the past in our country. CONCLUSIONS: EGWs inflict a severe negative impact on the quality of life. Owing to its notorious persistence and recurrence, healthcare professionals must educate patients on how to prevent the spread and recurrence, discuss details of available treatment modalities while keeping in view the psychological and sociological impact.

Adipokinetic Hormones Enhance the Efficacy of the Entomopathogenic Fungus Isaria fumosorosea in Model and Pest Insects.

Insect adipokinetic hormones (AKHs) are neuropeptides with a wide range of actions, including the control of insect energy metabolism. These hormones are also known to be involved in the insect defence system against toxins and pathogens. In this study, our aim was to demonstrate whether the application of external AKHs significantly enhances the efficacy of the entomopathogenic fungus Isaria fumosorosea in a model species (firebug Pyrrhocoris apterus) and pest species (Egyptian cotton leafworm Spodoptera littoralis and pea aphid Acyrthosiphon pisum). It was found that the co-application of Isaria with AKHs significantly enhanced insect mortality in comparison to the application of Isaria alone. The mode of action probably involves an increase in metabolism that is caused by AKHs (evidenced by the production of carbon dioxide), which accelerates the turnover of Isaria toxins produced into the infected insects. However, several species-specific differences probably exist. Intoxication by Isaria elicited the stimulation of Akh gene expression and synthesis of AKHs. Therefore, all interactions between Isaria and AKH actions as well as their impact on insect physiology from a theoretical and practical point of view need to be discussed further.

Biomechanical modelling and computer aided simulation of deep brain retraction in neurosurgery.

BACKGROUND AND OBJECTIVES: Surgical simulators are widely used to promote faster and safer surgical training. They not only provide a platform for enhancing surgical skills but also minimize risks to the patient's safety, operation theatre usage, and financial expenditure. Retracting the soft brain tissue is an unavoidable procedure during any surgery to access the lesioned tissue deep within the brain. Excessive retraction often results in damaging the brain tissue, thus requiring advanced skills and prior training using virtual platforms. Such surgical simulation platforms require an anatomically correct computational model that can accurately predict the brain deformation in real-time. METHODS: In this study, we present a 3D finite element brain model reconstructed from MRI dataset. The model incorporates precisely the anatomy and geometrical features of the canine brain. The brain model has been used to formulate and solve a quasi-static boundary value problem for brain deformation during brain retraction. The visco-hyperelastic framework within the theory of non-linear elasticity has been used to set up the boundary value problem. Consequently, the derived non-linear field equations have been solved using finite element solver ABAQUS. RESULTS: The retraction simulations have been performed for two scenarios: retraction pressure in the brain and forces required to perform the surgery. The brain was retracted by 5 mm and retained at that position for 30 minutes, during which the retraction pressure attenuates to 36% of its peak value. Both the model predictions as well as experimental observations on canine brain indicate that brain retraction up to 30 minutes did not cause any significant risk of induced damage. Also, the peak retraction pressure level indicates that intermittent retraction is a safer procedure as compared to the continuous retraction, for the same extent of retraction. CONCLUSIONS: The results of the present study indicate the potential of a visco-hyperelastic framework for simulating deep brain retraction effectively. The simulations were able to capture the dominant characteristics of brain tissue undergoing retraction. The developed platform could serve as a basis for the development of a detailed model in the future that can eventually be used for effective preoperative planning and training purposes.

A comparative study of the efficacy and safety of intralesional measles, mumps, and rubella vaccine versus intralesional vitamin D3 for the treatment of warts in children.

BACKGROUND: Intralesional vitamin D3 has recently emerged as a new treatment for cutaneous warts. The use of the measles, mumps, and rubella (MMR) vaccine for this purpose is an established modality. However, relevant data on the efficacy of either the MMR vaccine or vitamin D3 as immunotherapy for cutaneous warts in the pediatric population are limited. OBJECTIVES: To compare the efficacy and safety of intralesional injections of MMR vaccine to intralesional injections of vitamin D3 in children aged 8-16 years with multiple warts. METHODS: A total of 74 children were randomly allocated into two groups. Group A patients received intralesional MMR vaccine into the largest wart, and group B received intralesional vitamin D3 into the largest wart. The injections were repeated every 4 weeks until clearance or for a maximum of three treatments. After the last injection, children were followed up every 2 weeks for 3 months, and at the sixth month, a final clinical assessment was conducted. RESULTS: Of 74 children, 60 completed the study, with 30 children in each group. Complete clearance of the injected wart was observed in 26 (86.67%) patients in the MMR group (group A) and 23 (76.7%) patients in the vitamin D3 group (group B). Distant warts cleared in 23 (76.7%) patients in group A compared to 20 (66.6%) patients in group B. There was no significant difference between groups. No recurrence was seen in group A, whereas two (6.6%) children in group B exhibited recurrence in the ensuing 6-month follow-up. The most common adverse events were injection site pain and swelling. CONCLUSION: Both intralesional MMR and vitamin D3 are safe, generally well-tolerated, and equally effective in children for the treatment of cutaneous warts.

Adipokinetic hormone promotes infection with entomopathogenic fungus Isaria fumosorosea in the cockroach Periplaneta americana.

The adipokinetic hormones (AKHs) are known to be involved in insect immunity, thus their role in the cockroach Periplaneta americana infected with the entomopathogenic fungus Isaria fumosorosea was examined in this study. The application of I. fumosorosea resulted in a significant increase in both Akh gene expression and AKH peptide levels. Further, co-application of I. fumosorosea with Peram-CAH-II significantly enhanced cockroach mortality compared with the application of I. fumosorosea alone. The mechanism of AKH action could involve metabolic stimulation, which was indicated by a significant increase in carbon dioxide production; this effect can increase the turnover and thus efficacy of toxins produced by I. fumosorosea in the cockroach's body. I. fumosorosea treatment resulted in a significant decrease in haemolymph nutrients (carbohydrates and lipids), but co-application with Peram-CAH-II restored control level of lipids or even further increased the level of carbohydrates. Such nutritional abundance could enhance the growth and development of I. fumosorosea. Further, both I. fumosorosea and Peram-CAH-II probably affected oxidative stress: I. fumosorosea alone curbed the activity of catalase in the cockroach's gut, but co-application with Peram-CAH-II stimulated it. Interestingly, the hormone alone had no effect on catalase activity. Taken together, the results of the present study demonstrate the interactions between the fungus and AKH activity; understanding this relationship could provide insight into AKH action and may have practical implications for insect pest control in the future.

Effect of natural toxins and adipokinetic hormones on the activity of digestive enzymes in the midgut of the cockroach Periplaneta americana.

This study examined the effect of two natural toxins (a venom from the parasitic wasp Habrobracon hebetor and destruxin A from the entomopathogenic fungus Metarhizium anisopliae), and one pathogen (the entomopathogenic fungus Isaria fumosorosea) on the activity of basic digestive enzymes in the midgut of the cockroach Periplaneta americana. Simultaneously, the role of adipokinetic hormones (AKH) in the digestive processes was evaluated. The results showed that all tested toxins/pathogens elicited stress responses when applied into the cockroach body, as documented by an increase of AKH level in the central nervous system. The venom from H. hebetor showed no effect on digestive enzyme activities in the ceca and midgut in vitro. In addition, infection by I. fumosorosea caused a decrease in activity of all enzymes in the midgut and a variable decrease in activity in the ceca; application of AKHs did not reverse the inhibition. Destruxin A inhibited the activity of all enzymes in the midgut but none in the ceca in vitro; application of AKHs did reverse this inhibition, and no differences between both cockroach AKHs were found. Overall, the results demonstrated the variable effect of the tested toxins/pathogens on the digestive processes of cockroaches as well as the variable ability of AKH to counteract these effects.

Changes in vitellogenin expression caused by nematodal and fungal infections in insects.

This study examined the expression and role of vitellogenin (Vg) in the body of the firebug Pyrrhocoris apterus (Heteroptera, Insecta) during infection elicited by two entomopathogenic organisms, the nematode Steinernema carpocapsae and the fungus Isaria fumosorosea Infection by S. carpocapsae significantly upregulated Vg mRNA expression in the male body. The corresponding increase in Vg protein expression was also confirmed by electrophoretic and immunoblotting analyses. Remarkably, in females, the opposite tendency was noted. Nematodal infection significantly reduced both Vg mRNA and Vg protein expression levels in fat body and hemolymph, respectively. We speculate that infection of reproductive females reduces Vg expression to a level that is still sufficient for defense, but is insufficient for reproduction. This circumstance reduces energy expenditure and helps the individual to cope with the infection. Importantly, purified Vg significantly inhibited growth of Xenorhabdus spp., an entomotoxic bacteria isolated from S. carpocapsae. However, the effect of Vg against I. fumosorosea was not so obvious. The fungus significantly stimulated Vg gene expression in males; however, a similar increase was not recapitulated at the protein level. Nevertheless, in females, both mRNA and protein Vg levels were significantly reduced after the fungal infection. The obtained data demonstrate that Vg is probably an important defense protein, possibly with a specific activity. This considerably expands the known spectrum of Vg functions, as its primary role was thought to be limited to regulating egg development in the female body.

Seasonal variations of natural ventilation and radon-222 exhalation in a slightly rising dead-end tunnel.

The concentration activity of radon-222 has been monitored, with some interruptions, from 1997 to 2005 in the end section of a slightly rising, dead-end, 38-m long tunnel located in the Phulchoki hill, near Kathmandu, Nepal. While a high concentration varying from 6 x 10(3) Bq m(-3) to 10 x 10(3) Bq m(-3) is observed from May to September (rainy summer season), the concentration remains at a low level of about 200 Bq m(-3) from October to March (dry winter season). This reduction of radon concentration is associated with natural ventilation of the tunnel, which, contrary to expectations for a rising tunnel, takes place mainly from October to March when the outside air temperature drops below the average tunnel temperature. This interpretation is supported by temperature measurements in the atmosphere of the tunnel, a few meters away from the entrance. The temporal variations of the diurnal amplitude of this temperature indeed follow the ventilation rate deduced from the radon measurements. In the absence of significant ventilation (summer season), the radon exhalation flux at the rock surface into the tunnel atmosphere can be inferred; it exhibits a yearly variation with additional transient reductions associated with heavy rainfall, likely to be due to water infiltration. No effect of atmospheric pressure variations on the radon concentration is observed in this tunnel. This experiment illustrates how small differences in the location and geometry of a tunnel can lead to vastly different behaviours of the radon concentration versus time. This observation has consequences for the estimation of the dose rate and the practicability of radon monitoring for tectonic purposes in underground environments.