Early diagnosis of sickle cell retinopathy by using ocular coherence tomography in pediatric population (7-18 years) in central India.

BACKGROUND: Sickle cell disease (SCD) is the commonest inherited blood disorder leading to complications occurring due to vaso-occlusion including sight-threatening retinopathy. Retinopathy can be managed if diagnosed early and vision loss can be prevented. Since, very less data are available from India, hence, this study was conducted in children (7-18 years) with SCD to diagnose retinopathy by using ocular coherence tomography (OCT) in subclinical stages. METHODS: This cross sectional single-center study was performed in 7-18 years age group children with SCD without any visual symptoms. Enrolled participants underwent complete ophthalmological examination including macula and optic disc thickness measurements using Cirrus HD-OCT and results were analyzed. RESULTS: Among 55 participants, none had visual impairment. Significant fundoscopy finding (nonproliferative sickle cell retinopathy/NPSR) was found in three patients (5.4%), thinning of central macula in four patients (7.27%), inner macula thinning in eight patients (14.5%), outer macula thinning in one patient (1.81%), retinal nerve fiber layer thinning in five patients (9%), ganglion cell layer to inner plexiform layer thinning in eight patients (14.54%). Overall NPSR was found in 5.4% patients detected with fundoscopy, whereas retinal layer thinning was found in 14 patients (25.4%) using OCT. CONCLUSION: Despite of the significant prevalence of SCR, it is still underdiagnosed complication, leading to thinning of the retina from early ages; thus, its early diagnosis by regular screening using newer diagnostic methods can prevent progression to sight-threatening complications and provide better quality of life for these patients.

Background-suppressed live visualization of genomic loci with an improved CRISPR system based on a split fluorophore.

The higher-order structural organization and dynamics of the chromosomes play a central role in gene regulation. To explore this structure-function relationship, it is necessary to directly visualize genomic elements in living cells. Genome imaging based on the CRISPR system is a powerful approach but has limited applicability due to background signals and nonspecific aggregation of fluorophores within nuclei. To address this issue, we developed a novel visualization scheme combining tripartite fluorescent proteins with the SunTag system and demonstrated that it strongly suppressed background fluorescence and amplified locus-specific signals, allowing long-term tracking of genomic loci. We integrated the multicomponent CRISPR system into stable cell lines to allow quantitative and reliable analysis of dynamic behaviors of genomic loci. Due to the greatly elevated signal-to-background ratio, target loci with only small numbers of sequence repeats could be successfully tracked, even under a conventional fluorescence microscope. This feature enables the application of CRISPR-based imaging to loci throughout the genome and opens up new possibilities for the study of nuclear processes in living cells.

Effect of platelet-rich plasma versus steroid injection in plantar fasciitis: a randomized clinical trial.

BACKGROUND: Plantar fasciitis (PF) is a common orthopaedic problem, with heel pain worsening the quality of life. Although steroid injection is often used if the conservative treatment fails, Platelet-Rich Plasma (PRP) injection is gaining popularity due to its safety and long-lasting effect. However, the effect of PRP versus steroid injection in PF has not been studied yet in Nepal. Therefore, this study aimed to assess the effect of PRP compared with steroid injection in the treatment of PF. METHODS: This study was a single-center, hospital-based, open-label, parallel-group randomized clinical trial to compare the effect of PRP injection with steroid injection in plantar fasciitis between August 2020 and March 2022. A total of 90 randomly selected participants aged 18 to 60 years suffering from plantar fasciitis with failed conservative treatment were intervened. The American Orthopaedic Foot and Ankle Society (AOFAS) and the Visual Analog Scale (VAS) scoring system were used to evaluate functional mobility and pain before and after the intervention for three and six months, respectively. Statistical analyses were performed using a Student's two-sample t-test. P-value < 0.05 was considered statistically significant. RESULTS: The PRP injection showed a better outcome than the steroid injection in six months follow-up. The mean (± SD) VAS score was significantly decreased in the PRP group (1.97 + 1.13) than in the steroid group (2.71 ± 0.94) with the group difference of -0.73 (95% CI: -1.18 to -0.28) at six months. Similarly, there was a significant increase in the AOFAS scores in the PRP group (86.04 ± 7.45) compared to the steroid group (81.23 ± 9.60) at six months of follow-up with a group difference of 4.80 (95% CI: 1.15 to 8.45). There was also a significant reduction of plantar fascia thickness in the PRP group compared to that of the steroid group (3.53 ± 0.81 versus 4.58 ± 1.02) at six months of follow-up with the group difference of -1.04 (95% CI: -1.44 to -0.65). CONCLUSION: The PRP injection showed better outcomes than steroid injection in plantar fasciitis treatment over the course of six months. Further research with a larger population and longer follow-up than six months is needed to generalize the findings and their long-term efficacy. TRIAL REGISTRATION: NCT04985396. First registered on 02 August 2021. ( https://clinicaltrials.gov/ct2/show/NCT04985396 ).

The effect of pre-operative carbohydrate loading in femur fracture: a randomized controlled trial.

BACKGROUND: Femur fracture is a major burden among elderly people, leading patients to be bedridden for a long time in the hospital. The body is more likely to be in a catabolic state as a result of the prolonged fasting period required for surgery, leading to an increase in insulin resistance. Pre-operative carbohydrate loading has been shown to improve postoperative outcomes in several countries. The study aimed to evaluate the effect of pre-operative carbohydrate loading in femur fracture surgery. METHODS: This study was single-center, hospital-based, open-label, parallel-group randomized controlled trial conducted between August 2020 and November 2021. A total of 66 participants, aged 50 years and above having femur fractures planned for surgery were included in this study and assigned to the control (n = 33) and study (n = 33) groups through computer-generated random numbers. The control group was kept fasting from midnight to the next morning as in existence while the study group was intervened with carbohydrate loading according to the Enhanced Recovery After Surgery (ERAS) protocol. The pre-operative nutritional status was identified and the postoperative outcomes were measured using the Visual Analogue Score (VAS), Cumulative Ambulatory Score (CAS), and Modified Barthel Index (MBI) scoring systems. Statistical analyses were performed using the Chi-square test and the Student's two-sample t-test to compare the outcomes between the two groups. RESULTS: All the participants completed the study. There was a significant reduction in the average postoperative pain in the carbohydrate loading group (VAS: 4.8 (SD ± 1.8), 95% CI: 4.7-5.4) as compared to the control group (VAS: 6.1 (SD ± 2.1), 95% CI: 5.3-6.8). The average CAS showed a significant improvement in regaining the mobility function of participants in the study group (CAS: 8.1 (SD ± 2.8), 95% CI: 7.1-9.1) than that of the control group (CAS: 6.8 (SD ± 2.8), 95% CI: 5.8-7.8). The mean MBI score of the participants at the time of discharge from the hospital was higher in the study group (MBI:13.1 (SD ± 2.3), 95% CI: 12.2-13.9) compared to the control group (MBI: 11.8 (SD ± 3.1), 95% CI:10.6-12.9). Similarly, the length of hospital stay after surgery had decreased in the study group than in the control group. CONCLUSIONS: The uptake of carbohydrate loading showed reduced post-operative pain, enhanced functional mobility, and decreased length of hospital stay. This study warrants larger trials to show the effect of pre-operative carbohydrate loading in a clinical setting. TRIAL REGISTRATION: NCT04838366, first registered on 09/042021 ( https://clinicaltrials.gov/ct2/show/NCT04838366 ).

Palonosetron is a Better Choice Compared With Ondansetron for the Prevention of Chemotherapy-induced Nausea and Vomiting (CINV) in a Resource-limited Pediatric Oncology Center: Results From a Randomized Control Trial.

Palonosetron (PG) is a newer, safe, and effective long-acting 5-HT3 antagonist commonly used in adults, but data in children are limited. A randomized controlled trial was carried out among children with cancer during their first cycle of moderate or highly emetogenic chemotherapy to receive either PG or ondansetron (OG) with the aim of comparing their efficacy, safety, and cost-effectiveness. In total, 200 children (mean age, 8 y, male:female=1.8:1) were recruited, 100 in each arm. Complete response, defined as no vomiting, in acute (<24 h), delayed (24 to 120 h), and overall phases (0 to 120 h) was observed in 88%, 88%, and 81% of cases, respectively, for PG versus 84%, 79%, and 72%, respectively, for OG (P=0.42, 0.09 and 0.21, respectively). Complete protection rates, defined as no nausea and vomiting in children above 6 years of age, in acute, delayed, and overall phases were 84%, 81%, and 73%, respectively, for PG versus 79%, 67%, and 60%, respectively, for OG (P=0.44, 0.06 and 0.10, respectively). Overall, the efficacy and safety of PG in the prevention of chemotherapy-induced nausea and vomiting was comparable with OG, but PG was a more cost-effective and suitable choice for busy centers in resource-limited countries.

Histoplasma capsulatum Infection with Extensive Lytic Bone Lesions Mimicking LCH.

Multiple lytic bone lesions in a child can be a manifestation of various diseases like Langerhans cell histiocytosis, metastatic neuroblastoma, leukemia, hyperparathyroidism, multifocal osteomyelitis and histoplasmosis. Disseminated histoplasmosis caused by Histoplasma capsulatum var. duboisii is well known to present with multiple osteolytic lesions in immunocompromised adults and is mostly restricted to the African subcontinent. Histoplasmosis seen in American and Asian countries is caused by Histoplasma capsulatum var. capsulatum, which presents with pulmonary and systemic manifestations and rarely bone involvement. We report a case of histoplasmosis, caused by H. capsulatum var. capsulatum with extensive lytic bone lesions in a 13 year old immunocompetent boy who presented with prolonged fever, weight loss and multiple boggy swellings. He responded to amphotericin and is currently on Itraconazole. This case is unique for extensive osteolytic lesions with H. capsulatum var. capsulatum infection in an immunocompetent child.

Steroid-responsive anemia in patients of Ghosal hematodiaphyseal dysplasia: simple to diagnose and easy to treat.

Ghosal hematodiaphyseal dysplasia (GHDD) is a recently recognized cause of steroid-responsive anemia. We would like to report 3 cases of GHDD who presented in early childhood with moderate to severe anemia, splenomegaly, and a hypocellular marrow with increased reticulin. They were easily diagnosed with long-bone x-rays showing diaphyseal and metaphyseal widening and loss of diaphyseal constriction. All cases dramatically responded to oral steroid and no longer needed blood transfusion. They required steroid at low doses for long term (up to 5 y). GHDD is easy to diagnose with long-bone radiography and consistently responds to steroid. It should therefore be considered as a differential diagnosis of unusual anemia in early childhood, especially in children from the Middle East or the Indian subcontinent.

Theasaponin E1 as an effective ingredient for anti-angiogenesis and anti-obesity effects.

Theasaponin E1 (TSE1) has been suggested to have higher biological activity than other saponins present in tea seed. Saponins have recently been considered as a potential chemotherapeutic agent for treating cancer. We examined the anti-angiogenic and anti-obesity properties of TSE1 contributing to anti-cancer efficacy. Treating with a 10 µg/mL concentration of TSE1 completely inhibited tube formation in human umbilical vein endothelial cells (HUVECs). TSE1 showed toxicity toward cancer cells and inhibited in vivo growth of the tumor. The vascular endothelial growth factor (VEGF) receptor complex was suppressed, leading to the inhibition of protein kinase B (Akt) expression and down-regulation of nuclear factor-kappa B (NF-kB) activation. The differentiating 3T3-L1 cells treated with TSE1 had decreased lipid droplet formation measured by Oil Red O staining. Reduced weight was measured in mice fed with a TSE1 plus high-fat diet. The results taken together, and particularly the NF-kB inhibition, suggest that TSE1 may have multi-target action for treating cancer as a novel chemotherapeutic agent.

Immunomodulatory effect of tea saponin in immune T-cells and T-lymphoma cells via regulation of Th1, Th2 immune response and MAPK/ERK2 signaling pathway.

The anti-cancer activity of saponins and phenolic compounds present in green tea was previously reported. However, the immunomodulatory and adjuvanticity activity of tea saponin has never been studied. In this study, we investigated the immunomodulatory effect of tea saponin in T-lymphocytes and EL4 cells via regulation of cytokine response and mitogen-activated protein kinases (MAPK) signaling pathway. Quantitative analysis of mRNA expression level of cytokines were performed by reverse transcription polymerase chain reaction following stimulation with tea saponin, ovalbumin (OVA) alone or tea saponin in combination with OVA. Tea saponin inhibited the proliferation of EL4 cells measured in a dose-dependent manner. No cytotoxicity effect of tea saponin was detected in T-lymphocytes; rather, tea saponin enhanced the proliferation of T-lymphocytes. Tea saponin with OVA increased the expression of interleukin (IL)-1, IL-2, IL-12, interferon-γ and tumor necrosis factor (TNF)-α and decreased the expression level of IL-10 and IL-8 in T-lymphocytes. Furthermore, tea saponin, in the presence of OVA, downregulated the MAPK signaling pathway via inhibition of IL-4, IL-8 and nuclear factor kappaB (NF-κB) in EL4 cells. Th1 cytokines enhancer and Th2 cytokines and NF-κB inhibitor, tea saponin can markedly inhibit the proliferation and invasiveness of T-lymphoma (EL4) cells, possibly due to TNF-α- and NF-κB-mediated regulation of MAPK signaling pathway.

Prevalence of osteoporosis and associated factors among people aged 50 years and older in the Madhesh province of Nepal: a community-based cross-sectional study.

BACKGROUND: The high prevalence of osteoporosis has increased the economic burden on the health system globally. The burden of osteoporosis and its associated factors have not been adequately assessed in community settings in the Nepalese context thus far. Therefore, this study aimed to assess the prevalence of osteoporosis and its associated factors, lifestyle behaviors, and dietary calcium intake. METHODS: A community-based cross-sectional study was conducted among 395 people aged 50 years and older in the Madhesh Province of Nepal between July 2022 and August 2023. The Osteoporosis Self-assessment Tools for Asians (OSTA) index was used to measure osteoporosis. A structured questionnaire was used to collect sociodemographic information, anthropometric data, lifestyle behavior, daily dietary calcium intake, and frequency of calcium-rich food consumption. A food frequency questionnaire and 24-hour recall methods were used to assess dietary intake. The chi-square test, binary logistic regression and Mann‒Whitney U test were applied to measure the association between predictors and the outcome of interest. RESULTS: The prevalence of no risk, moderate risk and high risk of osteoporosis were 38.7%, 39%, and 22.3% respectively. The risk of osteoporosis was higher in females (aOR = 5.18, CI: 2.10-12.75, p < 0.001) and increased risk with advancing age (aOR = 32.49, CI: 14.02-75.28, p < 0.001). Similarly, underweight was associated with increased odds of having osteoporosis (aOR = 13.42, CI = 4.58-39.30, p < 0.001). The incidence of osteoporosis was strongly associated with daily calcium intake of 225 mg (100, 386). CONCLUSION: This study revealed a high prevalence of osteoporosis among people aged 50 years and older due to the combined effect of being underweight and having inadequate calcium intake. Nutritional counselling services encourage people to consume sufficient calcium-rich food and adopt an appropriate lifestyle behaviours to maintain healthy body weight so that osteoporosis and osteoporotic fractures could be prevented. Further research can explore the impact of socioeconomic status and medical comorbidities on a large scale.

Cytohistological findings and diagnostic challenges in rare pediatric pulmonary mesenchymal malignancies: A report of two cases.

Pulmonary mesenchymal tumors are uncommon neoplasms and the data available on their clinical, cytohistomorphological, immunohistochemical, and molecular findings are limited, leading to difficulty in timely diagnosis and management. Case 1: A 12-year-old boy presented with a right endobronchial mass. Imprint smears from endobronchial biopsy revealed moderately pleomorphic spindle cell tumor arranged in fascicles and perivascular pattern with attached myxoid material showing occasional mitotic activity suggesting a cytological diagnosis of sarcoma. Biopsy also displayed similar morphology. Extensive immunohistochemistry (IHC) showed diffuse SMA, focal AE1/AE3, and diffuse ALK positivity along with a MIB/Ki67 index of 30%-40% leading to the diagnosis of inflammatory myofibroblastic tumor (IMT; Sarcoma grade). Case 2: A 8-year-old boy presented with a huge left-sided mass replacing the entire lung parenchyma and eroding adjoining ribs. Pleural fluid cytology revealed vague clusters of PAS-positive diastase-sensitive small atypical cells with associated inflammatory cells in the hemorrhagic background, suggesting a diagnosis of malignant small round blue cell tumor. Trucut biopsy from the mass showed spindled to round cells showing diffuse positivity with CD99 and BCL-2. Molecular studies with reverse transcription-PCR (RT-PCR) for SYT-SSX and EWS-FLI1 were negative for synovial sarcoma and Ewing's sarcoma, respectively. Given the clinical setting, PAS positivity, IHC, and molecular studies, the diagnosis of tumors of uncertain differentiation with the possibility of Ewing's sarcoma family of tumors (ESFT) with a translocation between EWS1 and other ETS-family members (ERG, FEV, ETV1, E1AF, etc.) was suggested.

Data analysis for SEM-EDX, thermokinetics, surfactant, and corrosion inhibition activity of Co(II) and Zn(II) complexes of pyrrole-based surfactant ligand.

This manuscript reports a dataset for the scanning electron microscopy with energy dispersive X-ray analysis (SEM-EDX), surfactant properties, thermokinetics, and corrosion inhibition activity of [[Co(HL)2.2H2O] Cl2.H2O]] (1) and [[Zn(HL)2.Cl] Cl.3H2O]] (2) complexes with surfactant-based Schiff base ligand (HL). It contains analyzed data related to thermokinetics, such as the activation energy (E*), entropy change (∆S*), enthalpy change (∆H*), and free energy change (∆G*) of HL and metal complexes. It also contains the SEM micrographs and EDX images of the studied ligand and metal complexes. A detailed analysis of the critical micelle concentration (CMC) data and figures illustrating the surfactant behavior of the synthesized complexes are presented in this article. The data for the corrosion inhibition activity of all synthesized compounds are also included. The dataset is related to the research article entitled "Bioinorganic interest on Co(II) and Zn(II) complexes of pyrrole-based surfactant ligand: Synthesis, characterization, and in silico-ADME study".

Intramuscular ketamine provides better sedation and scan conditions in children undergoing magnetic resonance imaging: A single-blinded observational study.

Objectives: The objectives of this study were to compare the quality of sedation provided by intravenous (i.v.) and intramuscular (im) ketamine for pediatric magnetic resonance imaging (MRI). Materials and Methods: This study was a non-randomized, single-blinded, and prospective observational study. After receiving approval from the Institutional Ethics Committee, a total of 108 children aged 2-7 years were divided into two groups, with 54 children in each group. In the i.v. group, children received ketamine at a dose of 1.5 mg/kg intravenously, while in the im group, children received ketamine at a dose of 4 mg/kg intramuscularly. If a Ramsay sedation score of 6 (RSS-6) was not achieved, half of the loading dose of ketamine was repeated. In both groups, rescue propofol boluses of 1 mg/kg intravenously were administered whenever the child moved. The primary outcome measure was the quality of sedation, which was assessed by a blinded radiologist. The time taken to reach RSS-6, the number of rescue propofol boluses, the total time wasted in taking repeat sequences, and the time required to achieve a modified Aldrete score of 9 (MAS-9) were recorded. Results: The im group demonstrated significantly better sedation quality. In the i.v. group, the time to achieve RSS-6 was significantly shorter, but it required more rescue propofol boluses to maintain sedation. The i.v. group also experienced a notable increase in the total time wasted during repeat sequences. On the other hand, the i.v. group exhibited a shorter time to reach MAS-9 compared to the im group. Conclusion: The im group showed superior sedation quality when compared to the i.v. group. However, it is important to consider that the im group experienced a longer recovery time.

The factors influencing inappropriate child feeding practices among families receiving nutrition allowance in the Himalayan region of Nepal.

BACKGROUND: Child feeding practices during the first two years of life are crucial to ensure good health and nutrition status. This study aimed to assess the factors influencing inappropriate child feeding practices in children aged 6 - 23 months in families receiving nutrition allowance in the remote Mugu district, Nepal. METHODS: A community-based cross-sectional study was conducted among 318 mothers who had children aged 6 - 23 months of age in the seven randomly selected wards. Systematic random sampling technique was used to select the desired number of respondents. Data were collected using pre-tested semi-structured questionnaire. Bivariate and multivariable binary logistic regression was used to estimate crude odds ratio (cOR), and adjusted odds ratio (aOR), and 95% confidence intervals (CIs) to understand factor associated with child feeding practices. RESULTS: Almost half of the children aged 6 - 23 months were not consuming a diverse diet (47.2%; 95% CI: 41.7%, 52.7%), did not meet the recommended minimum meal frequency (46.9%; 95% CI: 41.4%, 52.4%) and did not consume minimum acceptable diet (51.7%; 95% CI: 46.1%, 57.1%). Only 27.4% (95% CI: 22.7%, 32.5%) of children met the recommended complementary feeding practices. Multivariable analysis showed maternal characteristics such as mothers who gave birth at home (aOR = 4.70; 95% CI: 1.03, 21.31) and mothers in unpaid employment (aOR = 2.56; 95% CI: 1.06, 6.19) were associated with increased odds of inappropriate child feeding practices. Household economy (i.e. family with < 150 USD monthly income) was also associated with increased odds of inappropriate child feeding practices (aOR = 1.19; 95% CI: 1.05, 2.42). CONCLUSION: Despite the receipt of nutritional allowances, child feeding practices among 6 - 23 months children were not optimal. Additional context-specific behavior change strategies on child nutrition targeting mothers may be required.

Intensified seed spices-based cropping systems for higher productivity, resource-use efficiency, soil fertility and profitability in arid and semi-arid regions of India.

Coriander, fenugreek, nigella etc. are collectively known as seed spices. They are "High value and low volume crops" and considered cash crops for the growers of arid and semi-arid regions of India. Coriander, fenugreek and nigella are grown during the rabi season and take hardly 130-140 days to attain full maturity. In this context, farmers are not able to develop income from available arable land round the year, even though they have sufficient resources as well as manpower. Therefore, coriander, fenugreek and nigella-based cropping systems, four of each (total 12) were evaluated during 3 consecutive years (2019-20 to 2021-22) for their productivity, resource-use efficiency, economics and soil fertility. The results showed that among the seed spices-based cropping systems, maximum system productivity (5193 kg ha-1), production efficiency (18.81 kg ha-1 day-1), water-use efficiency (2.31 kg ha-1 mm-1), economic efficiency (11.85 US $ ha-1 day-1), net return (3270 US $ ha-1), benefit:cost ratio (3.27) and available N (165.6 kg ha-1) were observed under nigella-green coriander-mungbean cropping system. Hence, seed spices growers are recommended to adopt nigella-green coriander-mungbean cropping system in order to realize better productivity, resource-use efficiency, soil fertility and profitability.

An assessment of childhood cancer care services in India - gaps, challenges and the way forward.

Background: Childhood cancers are emerging as an essential concern in India where there is lack of a specific programme component or policy to address childhood cancer control. There is limited information on the status and quality of childhood cancer care services in India. This paper describes the childhood cancer care services available at secondary and tertiary-level hospitals in India through a cross sectional study design. Methods: The survey was conducted in 137 tertiary-level and 92 secondary-level hospitals in 26 states and 4 Union Territories (UTs), ensuring a uniform representation of public and private care hospitals. The study tool collected data on the organisational infrastructure, type of oncology services, health workforce, equipment, treatment and referral protocols, and treatment guidelines. Descriptive statistics was used to primarily present the health service status and data on childhood cancer care services in proportions and mean. Findings: A dedicated pediatric oncology department was available in 41.6% of the public, 48.6% of private, and 64% Non Government Organization (NGO) managed tertiary-level hospitals. In 36 (39%) of the 92 hospitals providing secondary care, childhood cancer care was provided. The availability of bone (41.5%) and positron emission tomography (PET) scans (25.9%) was lower in public tertiary hospitals, whereas histopathology, computerised tomography (CT scan), and magnetic resonance imaging (MRI) were lower in public secondary hospitals than private and NGO managed hospitals for the corresponding level of care. Most tertiary hospitals had the required supportive care facilities except for play therapy and hospice care. Less than 50% of the public tertiary hospitals had stocks of the four categories of cancer-treating drugs and essential infrastructure for radiotherapy and chemotherapy. Most secondary-level hospitals not treating childhood cancer had referral linkages with tertiary hospitals. Interpretation: The situational analysis of childhood cancer care services in India showed the concentration of availability of childhood cancer care services at the tertiary level of health care. There were gaps in the availability of specialised pediatric oncology care in all the tertiary hospitals. The availability of childhood cancer care services was higher in private and NGO-managed hospitals than in public hospitals. Integration of childhood cancer as a part of the national cancer control response should be taken up as a matter of priority. The need of the hour is to formulate a childhood cancer policy that will enable timely access to care universally. Funding: World Health Organization, India provided funding and technical support.

Metronomic therapy for malignant peripheral nerve sheath tumor in neurofibromatosis type 1.

Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive tumor especially in the patients with neurofibromatosis type 1 (NF1). Without a complete surgical excision, prognosis is guarded. We describe a 10-year-old male with NF1 with MPNST, who had a local relapse within 5 weeks of surgical excision. Chemoradiotherapy did not result in tumor regression. Initiation of palliative oral metronomic therapy resulted in complete remission after six cycles. The patient continues to be in remission, 20 months after completion of nine cycles of metronomic therapy. Metronomic therapy may be effective in MPNST where conventional chemotherapy and radiotherapy fails.

Significance of interleukin-6 (IL-6) and C-reactive protein (CRP) in children and young adults with febrile neutropenia during chemotherapy for cancer: a prospective study.

OBJECTIVES: We evaluated the usefulness of interleukin-6 (IL-6) and C-reactive protein (CRP) at the onset of febrile neutropenia and 72 hours later, in identifying risk groups and assessing response to antibiotic therapy. METHODS: All episodes of febrile neutropenia were divided in 3 study groups-microbiologically documented infection (MDI), clinically documented infection (CDI), and fever of unknown origin (FUO). Three outcome groups were defined as those responding to first-line antibiotics (R1), those responding to second-line antibiotics (R2), and those requiring antifungal therapy (RAF). Median values of IL-6 and CRP were compared between the groups. RESULTS: There were 57 episodes of febrile neutropenia among 26 patients younger than 25 years during 1 year of study period. On day 1, median IL-6 level was significantly lower in FUO group compared with CDI+MDI groups combined (P < 0.001). Rise in CRP on day 3 was highly significant to differentiate MDI group from other 2 groups (P < 0.001). The CRP also increased significantly on day 3 in RAF (P < 0.001) and R2 (P = 0.002) groups than in R1 group. CONCLUSIONS: Low level of IL-6 may help differentiate patients with FUO from those with documented infections. A rising CRP is indicative of serious infection.

Maternal hemoglobin and risk of low birth weight: A hospital-based cross-sectional study in Nepal.

Background: Maternal hemoglobin during pregnancy is an important predictor of neonatal outcomes such as birth weight. The newborn weight of an infant is considered a crucial factor for morbidity and mortality. This study aimed to assess the association between maternal hemoglobin concentration and newborn weight at term pregnancy. Methods: A hospital-based cross-sectional study was conducted at Tribhuvan University Teaching Hospital (TUTH), Kathmandu, Nepal from 14th April 2018 to 13th April 2019. Term singleton pregnant women who were admitted for delivery in the labor room of TUTH were included in this study. Maternal characteristics such as age, parity, birth space, ethnicity, education level, dietary habit, body mass index (BMI), and hemoglobin level were recorded. The newborn weight was taken immediately after delivery. The main outcome of this study was the birth weight. The association between hemoglobin level and newborn weight was analyzed using bivariate and multivariable logistic regression analysis. Results: Of 2,418 term pregnant women, the prevalence of low hemoglobin and high hemoglobin levels were 24% (95% CI: 22-25.4), and 17% (95% CI: 15.7-18.7), respectively. The prevalence of low birth weight (LBW) was 12.9% (95% CI: 11.7-14.4). Multivariable logistic regression analysis showed that those mothers who had low hemoglobin concentration (adjusted Odds Ratio/aOR = 3.77, 95% CI: 2.84-5.01), and high hemoglobin concentration (aOR = 3.07, 95% CI: 2.23-4.24) had higher odds of having LBW compared to mothers having normal hemoglobin level. Mothers with both young age pregnancy (aged 16-20 years) and older pregnancy (aged ≥31 years) (aOR = 1.60, 95% CI: 1.01-2.52) and (aOR = 1.60, 95% CI: 1.06-2.41), respectively had higher odds of LBW compared to mothers aged 21-25 years. Those mothers who attended a primary level of education had higher odds of (aOR = 1.93, 95% CI: 1.05-3.55) LBW compared to those mothers with a higher level of education. Moreover, mothers who belonged to Janajati ethnic group (aOR = 0.47, 95% CI: 0.34-0.65) compared to the Brahmin/Chhetri ethnic group, and mothers with a birth space of more than three years (aOR = 0.63, 95% CI: 0.41-0.97) compared to those who had less than three years of birth spacing and mothers who were overweight/obese (aOR = 0.74, 95% CI: 0.55-0.99) compared to normal nutritional status had lower odds of having LBW. Conclusions: Our study concludes that both low and high hemoglobin had an increased risk of having low birth weight. Policies and programs can benefit by adopting the findings of this study. More empirical research is critical to understanding the impact of hemoglobin levels on birth weight.

Visualizing Live Chromatin Dynamics through CRISPR-Based Imaging Techniques.

The three-dimensional organization of chromatin and its time-dependent changes greatly affect virtually every cellular function, especially DNA replication, genome maintenance, transcription regulation, and cell differentiation. Sequencing-based techniques such as ChIP-seq, ATAC-seq, and Hi-C provide abundant information on how genomic elements are coupled with regulatory proteins and functionally organized into hierarchical domains through their interactions. However, visualizing the time-dependent changes of such organization in individual cells remains challenging. Recent developments of CRISPR systems for site-specific fluorescent labeling of genomic loci have provided promising strategies for visualizing chromatin dynamics in live cells. However, there are several limiting factors, including background signals, off-target binding of CRISPR, and rapid photobleaching of the fluorophores, requiring a large number of target-bound CRISPR complexes to reliably distinguish the target-specific foci from the background. Various modifications have been engineered into the CRISPR system to enhance the signal-to-background ratio and signal longevity to detect target foci more reliably and efficiently, and to reduce the required target size. In this review, we comprehensively compare the performances of recently developed CRISPR designs for improved visualization of genomic loci in terms of the reliability of target detection, the ability to detect small repeat loci, and the allowed time of live tracking. Longer observation of genomic loci allows the detailed identification of the dynamic characteristics of chromatin. The diffusion properties of chromatin found in recent studies are reviewed, which provide suggestions for the underlying biological processes.