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Over the last decades, various tissue-clearing techniques have broken the ground for the optical imaging of whole organs and whole-organisms, providing complete representative data sets of three-dimensional biological structures. Along with advancements in this field, the development of fluorescent markers for staining vessels and capillaries has offered insights into the complexity of vascular networks and their impact on disease progression. Here we describe the use of a modified water-soluble chitosan linked to cyanine dyes in combination with ethyl cinnamate-based optical tissue clearing for the 3D visualization of tissue vasculature in depth. The water-soluble fluorescent Chitosans have proven to be an optimal candidate for labeling both vessels and capillaries ex vivo thanks to their increased water solubility, high photostability, and optical properties in the near-infrared window. In addition, the nontoxicity of these markers broadens their applicability to in vitro and in vivo biological applications. Despite the availability of other fluorescent molecules for vascular staining, the present study, for the first time, demonstrates the potential of fluorescent chitosans to depict vessels at the capillary level and opens avenues for advancing the diagnostic field by reducing the complexity and costs of the currently available procedures., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Co-published by Nanjing University and American Chemical Society.)

We addressed if hyperfiltration can be assessed transcutaneously in male diabetic obese mice (BTBR ob/ob ) at 12 and 24 wk and how this relates to glomerular parameters indicative for hyperfiltration. Transcutaneous assessment of FITC-Sinistrin clearance [transcutaneous assessment of glomerular filtration rate (tGFR)] was compared against classical plasma clearance. Kidney from SV620C-01-PEI perfused mice were harvested at 24 wk and processed for tissue clearing and classical histology. Perfusion patterns of glomerular capillaries, glomerular size, and vasodilation of the afferent arterioles were assessed. Although at 12 wk FITC-Sinistrin half-life (t 1/2 ) for both tGFR and plasma clearance suggested hyperfiltration, this was not significant anymore at 24 wk. In kidneys of diabetic mice the diameter of the afferent arteriole was significantly larger and positively correlated with glomerular size. Glomerular perfusion pattern in these mice was heterogeneous ranging from non- to well-perfused glomeruli. Nonperfused glomerular areas displayed a strong periodic acid-Schiff's (PAS) positive staining. Collectively our data demonstrate that tGFR is a valid method to detect hyperfiltration. Hyperfiltration occurs early in BTBR ob/ob mice and disappears with disease progression as a consequence of a reduced filtration surface. It remains to be assessed if tGFR is also a valid method in diabetic mice with severely compromised renal function. NEW & NOTEWORTHY tGFR measurement is a relatively new method to assess kidney function in conscious rodents, which can be repeated multiple times in the same animal to track the course of the disease and/or the effect of potential treatments. Since the literature was inconclusive on the suitability of this technique in obese mice, we validated it for the first time against classical plasma clearance in the commonly used BTBR ob/ob mouse model.

Pancytopenia in children with celiac disease (CeD) is postulated to be due to nutritional deficiency such as vitamin B 12 , folate and copper or an autoimmune process resulting in aplastic anemia with hypoplastic marrow. In the present case series, we report the profile and explore the etiology of pancytopenia among children with CeD. There are only a few case reports of pancytopenia in children with CeD. We enrolled newly diagnosed cases of CeD and pancytopenia presenting in the celiac disease clinic over three years. Detailed evaluation was carried out for the cause of pancytopenia. We followed up on the cases for compliance and response to gluten-free diet at three months, six months and 12 months. Twenty patients were eligible for inclusion. They were divided into two groups: one with aplastic anemia with hypoplastic marrow labeled as Gp CeD-AA and the other with megaloblastic/nutritional anemia labeled as Gp CeD-MA. Patients in Gp CeD-MA presented with classical symptoms of CeD as recurrent diarrhea, abdomen distension, pallor and poor weight gain. They had none or just one transfusion requirement and had an early and complete recovery from pancytopenia. Patients in Gp CeD-AA presented with atypical symptoms such as epistaxis, short stature, fever, pallor and weakness. They had a multiple blood transfusion requirement and had delayed and partial recovery from pancytopenia. Pancytopenia is not a disease in itself but is the presentation of an underlying disease. It can occur due to various coexisting disorders in children with CeD, which can be as simple as nutritional deficiencies to as complex as an autoimmune process or malignancy. CeD should be included in the differential diagnosis of aplastic anemia as CeD and aplastic anemia both have a similar pathological process involving T cell destruction of tissues., (© 2023. Indian Society of Gastroenterology.)

Dysregulation in glomerular hemodynamics favors hyperfiltration in diabetic kidney disease (DKD). Although carnosine supplementation ameliorates features of DKD, its effect on glomerular vasoregulation is not known. We assessed the influence of carnosine and carnosinase-1 (CN1) on afferent glomerular arteriole vasodilation and its association with glomerular size, hypertrophy, and nephrin expression in diabetic BTBR ob/ob mice. Two cohorts of mice including appropriate controls were studied: i.e., diabetic mice that received oral carnosine supplementation ( cohort 1 ) and human (h)CN1 transgenic (TG) diabetic mice ( cohort 2 ). The lumen area ratio (LAR) of the afferent arterioles and glomerular parameters were measured by conventional histology. Three-dimensional analysis using a tissue clearing strategy was also used. In both cohorts, LAR was significantly larger in diabetic BTBR ob/ob versus nondiabetic BTBR wt/ob mice (0.41 ± 0.05 vs. 0.26 ± 0.07, P < 0.0001 and 0.42 ± 0.06 vs. 0.29 ± 0.04, P < 0.0001) and associated with glomerular size ( cohort 1 : r = 0.55, P = 0.001 and cohort 2 : r = 0.89, P < 0.0001). LAR was partially normalized by oral carnosine supplementation (0.34 ± 0.05 vs. 0.41 ± 0.05, P = 0.004) but did not differ between hCN1 TG and wild-type BTBR ob/ob mice. In hCN1 TG mice, serum CN1 concentrations correlated with LAR ( r = 0.90, P = 0.006). Diabetic mice displayed decreased nephrin expression and increased glomerular hypertrophy. This was not significantly different in hCN1 TG BTBR ob/ob mice ( P = 0.06 and P = 0.08, respectively). In conclusion, carnosine and CN1 may affect intraglomerular pressure in an opposing manner through the regulation of afferent arteriolar tone. This study corroborates previous findings on the role of carnosine in the progression of DKD. NEW & NOTEWORTHY Dysregulation in glomerular hemodynamics favors hyperfiltration in diabetic kidney disease (DKD). Although carnosine supplementation ameliorates features of DKD, its effect on glomerular vasoregulation is not known. We assessed the influence of carnosine and carnosinase-1 (CN1) on afferent glomerular arteriole vasodilation and its association with glomerular size, hypertrophy, and nephrin expression in diabetic BTBR ob/ob mice. Our results provide evidence that carnosine feeding and CN1 overexpression likely affect intraglomerular pressure through vasoregulation of the afferent arteriole.

Aim: To study the effectiveness of anterior and middle superior alveolar nerve block (AMSA) for anesthesia of unilateral maxillary teeth, i.e., from central incisor to second premolar of the same side by using conventional syringe and needle., Material and Method: Two hundred patients who needed extraction of any tooth/teeth in the region of central incisor to second premolar of the same side were randomly chosen for the study., Result: Successful anesthesia was found in 71.5% of cases. However, the highest success rate was seen with first premolar (82.2%) and minimum with lateral incisor (67.5%), and induction time ranged from 6 to 12 min and duration for 30-45 min., Conclusion: Using conventional syringe and needle, AMSA can be administered to achieve adequate soft tissue anesthesia of maxillary central incisors, canine and premolars of that side and pulpal anesthesia to a good extent (more so with first premolar), without affecting the muscles of facial expressions and lip numbness, reducing the requirement of multiple injections for the same., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Association of Oral and Maxillofacial Surgeons of India 2020.)

Objectives: To estimate the proportion of rotavirus diarrhea among hospitalized children aged under-five years, to determine the circulating rotavirus genotypes and to know impact rotavirus vaccine on prevalence and severity of rotavirus diarrhea., Methods: This study was a hospital based cross-sectional observational study conducted over a period of 29 mo (September 2017 through January 2020). Stool samples were collected from children who fall within the age range of 0-59 mo with acute diarrhea attending emergency or needing admission. Stool samples were tested for rotavirus by the enzyme linked immune-sorbent assay (ELISA) and genotyped using published methods., Results: Out of 1480 samples, 360 (24.32%) cases were positive for rotavirus by ELISA, majority of them were male (62.97%). Maximum rotavirus positivity was found in the age group of <11 mo (55.27%). Statistically significance difference was seen in episodes of diarrhea and experience of vomiting in rotavirus diarrhea cases. Highest prevalence has been seen during winter season. The most prevalent G and P type combinations were G3P [8] strains [122 (34.08%)], G2P [4] [83 (23.18%)], G1P [8] [27 (7.54%)] and G9P [4] [20 (5.59%)]. Mixed strains contribute a significant proportion of stool sample., Conclusions: Rotavirus is an important cause of diarrhea in hospitalized children. There is continued circulation of G9 and G12 strains and the emergence of G3P [8] as most common strain.

Neonatal hepatitis with acute liver failure due to varied etiology including various infections is reported in the past. Scrub typhus as a cause of neonatal hepatitis has rarely been reported in literature. A high index of clinical suspicion is required for early diagnosis and timely treatment. Severity and prognosis of the disease varies widely because several different strains of Orientia tsutsugamushi exist with different virulence. Delayed diagnosis can result in complication and significant morbidity and mortality. Here, we report three cases of neonatal hepatitis with acute liver failure caused by scrub typhus to increase awareness.

Purpose: To study whether breastfeeding and breastfeeding status during gluten introduction influences the age at diagnosis of celiac disease (CD). In addition to study, whether the timing of gluten introduction influences the age at diagnosis of CD., Methods: It was a hospital based observational study. Total 198 patients diagnosed with CD as per modified European Society of Pediatric Gastroenterology, Hepatology and Nutrition (2012) criteria, aged between 6 months to 6 years were included. Detail history taken with special emphasis on breastfeeding and age of gluten introduction. Standard statistical methods used to analyze the data., Results: Mean±standard deviation age of onset and diagnosis of CD in breastfed cases was 2.81±1.42 years and 3.68 ±1.55 years respectively as compared to 1.84±1.36 years and 2.70±1.65 years respectively in not breastfed cases ( p <0.05). Those who had continued breastfeeding during gluten introduction and of longer duration had significantly delayed onset of disease. The age at onset of CD was under one year in 40.42% of the cases, who had started gluten before 6 months of age compared to only 12.58% of those who had started gluten later ( p <0.001). The proposed statistical model showed that two variables, i.e., breast feeding status during gluten introduction and age at gluten introduction positively influencing the age at diagnosis of CD., Conclusion: Delayed gluten introduction to infant's diet along with continuing breastfeeding, delays symptomatic CD. However, it is not clear from our study that these infant feeding practices provide permanent protection against the disease or merely delays the symptoms.

A film-terminated fibrillar interface has been shown to result in significant enhancement of adhesion and static friction compared to a flat control. This enhancement increases with interfibril spacing. In this, the first of a two-part study, by studying the effect of rate on adhesion and static friction, we show that both adhesion and static friction enhancement are due to a crack-trapping mechanism. For adhesion, as measured by an indentation experiment, an analytical model is used to relate the applied indenter displacement rate and measured forces to contact line velocity and energy release rate, respectively. The two mechanisms for adhesion enhancement--varying rate and crack-trapping--are found to be coupled multiplicatively.

We present a model-independent method for extraction of adhesion energy from indentation experiments in which force, deflection, and contact area are measured. It is based on calculating the difference between external work supplied and stored strain energy, the deficit, which is assigned as work expended in opening (or closing) an interface. The critical step in the method is determination of the elastic indentation response without adhesion, using measured compliance. We show that this model-independent method accurately reproduces results obtained using the Johnson-Kendall-Roberts theory when it is applicable, and is particularly useful when an analytical contact mechanics solution is unavailable.

Water soluble dried powder of alcoholic extract of roots and rhizomes of A. calamus L. was used. The in vivo experiments involved strychnine convulsant activity in frogs, spontaneous motor activity and amphetamine hyperactivity in mice, pentobarbitone sleeping-time in rats and local anaesthetic activity in guinea pigs and rabbits. Frog skeletal muscle and heart preparations and rat phrenic nerve diaphragm constituted the in vitro experiments. Plant extracts at 10, 20 mg/kg ip did not afford protection to strychnine (1,5,2.5 mg/kg) induced convulsions and same effect was found on acetylcholine induced contractions of rectus muscle except that it inhibited caffeine citrate contractions in frog. At 1, 10 and 100 micrograms/ml doses, it caused negative iono- and chronotropic effects in frogs. Dosages of 10, 25, 50 mg/kg ip of herbal extract antagonize spontaneous motor activity and also amphetamine induced hyperactivity in mice. It was less potent than chloropromazine, though exerts sedative and tranquilizing action. Local anaesthetic activity was found to be absent at 0.5 and 1% dose levels.