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Introduction: COVID-19 highly contagious viruses that have reached every corner of the world. Despite the heroic efforts to control the pandemic, health care professional risk for COVID-19 exposure was an important measure to identify due to lack of personal protective equipment. The objective of the study was to find out the prevalence of healthcare professionals providing direct care to the COVID-19 patient., Methods: A descriptive cross-sectional was conducted through online questionnaire from June 2020 to August 2020. Ethical approval was obtained from the Ethical Review Board of Nepal Health Research Council (Reference number: 363/2020 P). World Health Organization risk assessment protocol questionnaire was used for COVID-19 and distributed among 300 health care workers of Nepal involved in the management of COVID-19 hospitals. Convenience sampling was used. The KoBo toolbox was used for online data collection. Data analysis was done using Statistical Package for the Social Sciences version 23. Point estimate at 95% Confidence Interval was calculated along with frequency and percentage for binary data., Results: Among 300 study participants, 109 (36.33%), (30.85-41.74 at 95% Confidence Interval) of participants provide direct care to infected patients. With total respondents, 41 (37.61%) were registered nurses, medical doctors 28 (25.68%) and paramedics 36 (33.02%)., Conclusions: Health care workers who provide direct care to the COVID-19 patient were similar to other studies done in similar settings. About half of the participants were exposed to COVID-19 virus from the hospital setting rather than from community setting which is similar to the study done in similar setting which might be due to lack of follow of protocols during COVID-19 patient care.

Introduction: Hip spica with or without prior traction has become a standard treatment for closed isolated femoral shaft fracture in children below six years. The time of hip spica application is not uniform in the existing literature. The aim of this study is to find out the prevalence of complication of early application of one and a half hip spica for femoral shaft fractures in children below six years in a tertiary care hospital. Methods: A descriptive cross-sectional study was done among 42 children who were managed with early hip spica application (within 72 hours) for femoral shaft fracture from January 2015 to December 2020 after receiving ethical clearance from Institutional Review Committee. Convenient sampling technique was done. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. Results: Complication was seen in nine (21.4%) (95% Confidence Interval= 9.02-33.84) patients. Skin breakdown from local pressure had the highest prevalence in our study which was documented in three (7.14%) patients who resolved with conservative treatment. Conclusions: The prevalence of complication of early application of one and a half hip spica for femoral shaft fractures in children below six years was similar to other studies done in similar setting.

Objective: To know the prevalence of rotavirus among hospitalized <5 y children, their demographic profile and genotypic distribution of rotavirus strain from tertiary care center of rural Haryana., Methods: An observational 3-year study done from June 2016 to June 2019 where children under 5 y of age hospitalized for acute gastroenteritis were enrolled. Various demographic, environmental, and clinical parameters were assessed. Stool samples were collected and sent to CMC, Vellore for rotavirus screening by enzyme immune assay (EIA) and RV-positive samples were genotyped using reverse transcription-polymerase chain reaction (RT-PCR)., Results: Out of 444 stool sample screened, 107 were positive (24.1%) for rotavirus. RV positive cases seen mostly in 6-24 mo age group with moderate to severe dehydration at presentation and peaks in winter months (Dec - Feb). G3P[8] (35.24%) is the most prevalent genotype identified followed by G1P[8] (20.95%), G1P[6] (11.43%), G2P[4] (6.67%) and G12P[8] (2.86%)., Conclusion: Continuous surveillance is required to monitor the circulating genotypes in postvaccination phase and assess the effectiveness and impact of the vaccine.

Introduction: The coronavirus disease 2019  pandemic is one of the biggest public health challenges that we have faced, and has had a significant impact on the delivery of essential healthcare worldwide. Trauma and orthopaedic surgery was one of the most severely affected specialties as all non-emergency surgical cases were cancelled. With the possibility of future peak of corona virus, knowing the impact of Covid on orthopaedics would enable us to manage trauma patient in an effective manner and will help us to resume normal schedule of the trauma care., Methods: This is a descriptive cross-sectional study. We studied the details of total number of patient at Orthopaedic and trauma outpatient, inpatient and operation theatre of Karnali Academy of Health Sciences from 14th March 2020 to 16 September 2020 as compared with the patient data from the same time period in 2019., Results: There were 2288 patients during the non-Covid period who visited to the orthopaedic outpatient in comparison to 1618 during Covid period. Only 5 implant removals were performed in comparison to 50 removals (90% reduction) in elective cases. But the number of surgical cases was almost similar (204 vs 207 respectively). Total number of hospital stay had significantly reduced in the non-COVID period (average 4 days vs 6 days).There were 181 in-patient admissions during the COVID period while 241 admission during the non-COVID period., Conclusions: There is reduction in number of orthopaedic and trauma cases during COVID 19 with marked reduction in number of elective cases. Alternative methods of treatment like telemedicine and small scale health camps at peripheral districts should be conducted to treat non-urgent orthopaedic conditions during lockdown.

Background: Chronic unreduced dislocation of elbow is a rare injury. Treatment options include open reduction internal fixation with K wire, replacement arthroplasty, excisional arthroplasty, arthrodesis, and hinged external fixator. The aim of this study is to determine the outcome of open reduction internal fixation with trans-olecranon K wire for neglected elbow dislocation., Methods: This is a retrospective study done in three rural hospital of Karnali. Hospital records were reviewed from July 2015 to May 2018 to identify 11 cases who underwent open reduction internal fixation for neglected elbow dislocation. Pre and Postoperative outcome was assessed using range of motion and Mayo Elbow Performance Index. Data analysis was done using SPSS version 17., Results: The average age of patient was 22.7 years (range 9-50 years). Non dominant hand was involved in 54.55%. The average preoperative elbow extension was 5.9 degree whereas postoperative extension was 15.9 degree. The average preoperative and postoperative elbow flexion was 24.5? and 113.6? respectively. Preoperative and postoperative Mayo elbow performance index was 18.6 and 86.3 respectively. Outcome was excellent in four patients, good in five patients and fair in two patients with one case having superficial infection., Conclusions: Open reduction and internal fixation with trans-olecranon k wire is an effective treatment method for neglected elbow dislocation. Postoperatively, elbow function is better with minimal complications.

Introduction: Femur fracture in children is one of the most common lower limb fractures which require inpatient care. The aim of this study is to determine the epidemiology of femoral shaft fractures in children from a rural population of Karnali Nepal., Methods: Hospital records were retrospectively reviewed from May 2017 to April 2020 to identify all the children with femur fracture. Sociodemographic profile, mode of injury, fracture pattern and location, time of presentation, initial treatment by traditional bone setters, treatment method and duration of hospital stay were noted. Data analysis was done using Statistical Package for Social Sciences version 20., Results: Altogether 104 children were identified. The mean age was 5.55 years and boys predominated 65 (62.5%). Falls were the major mode of injury in 65 (62.4%) patients. Fractures were frequently noted between April 15 to August 15. There were four (3.8%) open fractures and concurrent fracture observed in eight (7.6%) patients. Ten (9.6%) children received prior treatment from traditional bonesetters. Treatment methods included hip spica 62 (59.6%), elastic intramedullary nailing 30 (28.8%) and plate fixation 12 (11.5%). The duration of hospital stay in the nailing and plate fixation group was 11.43 days and 18 days respectively., Conclusions: Fracture was common in 2-6 years of age group in boys during summer. Fall from cliff, rooftop and ladder were the major preventable cause of fracture. Delayed presentation and prior treatment with traditional bone setters add special challenges to orthopedic surgeons working in rural teaching hospital.

Background: The purpose of this study is to compare the clinical and radiological outcome of medial versus posterior triceps splitting approach in open reduction internal fixation of displaced supracondylar fracture of humerus in children., Methods: A retrospective review of total 70 children with medial approach (n=30) and posterior triceps splitting approach (n=40) children was made. Time to radiological union, postoperative Bauman's angle and Lateral humerocapitellar angle was compared for radiological outcome. Cosmetic and functional outcome was assessed and compared using Flynn's criteria., Results: Radiological parameters like time to union, postoperative Bauman's angle and Lateral humerocapitellar angle were similar and non-significant between medial and posterior triceps splitting approach. Flynn's cosmetic outcome was similar between these approach (p=0.198). Loss of ROM was significant in posterior triceps splitting approach (p=0.00). Flynn's functional outcome was better with medial approach as compared to posterior triceps splitting approach with statistical significance (p=0.00)., Conclusions: Medial approach has better functional outcome compared to posterior triceps splitting approach in open reduction internal fixation of displaced supracondylar fracture of humerus in children.

Introduction: Supracondylar fracture of humerus is one of the common pediatric fractures encountered in our daily clinical practice. The purpose of this study is to determine the pattern of supracondylar fracture operated at rural teaching hospital of Jumla, Karnali Nepal., Methods: A descriptive cross sectional study was conducted at Jumla, Karnali after Institutional Review Committee approval. Operating room notes from 15 May 2017 to 16 November 2019 were retrieved to gather the following information: patients address, age, sex, side, injury mechanism, displacement, neurovascular injury, concurrent injuries, initial management by traditional bone setters, time between injury and surgery, operative technique. Data analysis was done using Statistical Package for Social Sciences version 20., Results: Left side predominated with 88 (63.7%) and extension type was common in 135 (97.8%). Thirteen (9.4%) patients were initially managed by traditional bonesetters. A total of 138 children underwent operative fixation with mean age of 7.47 years and gender ratio of 2:1 boy to girl. Fall from cliff, ladders and rooftops were the prevailing cause of injury 73 (52.8%). Average time between injury and surgery was 5.2 days. Closed reduction was done in 100 (72.4%) patients whereas open reduction was necessary in 38 (27.5%) patients., Conclusions: Closed extension type pediatric supracondylar fracture was common in this study. Fall from cliff, rooftop and ladder are the major cause of fracture. Delayed presentation and initial management of the fracture by the traditional bonesetters makes supracondylar fracture more challenging in resource limited setting like ours.

The purpose of this review is to discuss the challenges associated with the development of nanoparticle-based quality drug products in adhering to the principles of quality by design (QbD) and defining appropriate quality parameters towards successful product development. With the advent of nanotechnology into the pharmaceutical field, the novel field of nanomedicine was born. Due to their unique properties in terms of size, conformation and targeted delivery, nanomedicines are able to overcome many drawbacks of conventional medicine. As nano-sized formulations have made their way into more and more therapies, it has became clear that these very unique properties create hurdles for nanomedicines in successfully traversing the regulatory pathways and there is a need to develop nanomedicines in a more controlled and consistent fashion. The elements of a QbD methodology explained in this review enable the development of nano-based formulations in a way that maximizes the possibility of success. The identification of critical quality attributes (CQA) of the drug product and its intermediates are discussed in detail with a focus on nanomaterial-based formulations. In conclusion, QbD and the identification and specification of CQAs at its core are critical to the design, development and growth of nanomaterials in pharmaceuticals.

Introduction: Lateral condyle fracture of the distal humerus is the second most common paediatric elbow fracture. Unstable, rotated and displaced (>2 mm) fractures are managed with open reduction and internal fixation with Kirschner's wires or screws. Debate persists as for how long the Kirschner's wires should be placed in situ after internal fixation. We aimed to compare the functional and radiological outcome after early versus late removal of internally fixated Kirschner's wires for displaced lateral condyle fracture of distal humerus., Methods: Children that underwent early (3-4 weeks) or late (5-7 weeks) removal of Kirschner's wire after open reduction and internal fixation for displaced lateral condyle fracture of humerus were observed for a period of minimum 6 months. Time to radiological union, carrying angle, range of motion was assessed and compared between early and late group. Functional outcome was compared using the Dhillon scoring system., Results: We report the outcome of 40 cases (20 cases in each early and late group). Radiological union was achieved in all the cases of both group at 12 weeks follow up. The mean loss of carrying angle was statistically insignificant ( p = 0.394) between the early and late group. There was no significant difference between the early and late group in relation to arc of motion at 12 weeks ( p =0.724) and 6 months ( p =0.638) follow up. Using the Dhillon scoring system, there was 100% excellent Dhillon score in early group, 80% excellent and 20% good Dhillon score in late group. Functional outcome was statistically insignificant between the two groups ( p = 0.106)., Conclusion: Early removal of internally fixated K-wires for displaced lateral condyle fracture of humerus in children showed similar radiological and functional results to late removal.

Pharmacological ascorbate (AscH(-)) selectively induces cytotoxicity in pancreatic cancer cells vs normal cells via the generation of extracellular hydrogen peroxide (H2O2), producing double-stranded DNA breaks and ultimately cell death. Catalytic manganoporphyrins (MnPs) can enhance ascorbate-induced cytotoxicity by increasing the rate of AscH(-) oxidation and therefore the rate of generation of H2O2. We hypothesized that combining MnPs and AscH(-) with the chemotherapeutic agent gemcitabine would further enhance pancreatic cancer cell cytotoxicity without increasing toxicity in normal pancreatic cells or other organs. Redox-active MnPs were combined with AscH(-) and administered with or without gemcitabine to human pancreatic cancer cell lines, as well as immortalized normal pancreatic ductal epithelial cells. The MnPs MnT2EPyP (Mn(III)meso-tetrakis(N-ethylpyridinium-2-yl) porphyrin pentachloride) and MnT4MPyP (Mn(III)tetrakis(N-methylpyridinium-4-yl) porphyrin pentachloride) were investigated. Clonogenic survival was significantly decreased in all pancreatic cancer cell lines studied when treated with MnP + AscH(-) + gemcitabine, whereas nontumorigenic cells were resistant. The concentration of ascorbate radical (Asc(•-), an indicator of oxidative flux) was significantly increased in treatment groups containing MnP and AscH(-). Furthermore, MnP + AscH(-) increased double-stranded DNA breaks in gemcitabine-treated cells. These results were abrogated by extracellular catalase, further supporting the role of the flux of H2O2. In vivo growth was inhibited and survival increased in mice treated with MnT2EPyP, AscH(-), and gemcitabine without a concomitant increase in systemic oxidative stress. These data suggest a promising role for the use of MnPs in combination with pharmacologic AscH(-) and chemotherapeutics in pancreatic cancer., (Published by Elsevier Inc.)

Labile iron, i.e. iron that is weakly bound and is relatively unrestricted in its redox activity, has been implicated in both the pathogenesis as well as treatment of cancer. Two cancer treatments where labile iron may contribute to their mechanism of action are pharmacological ascorbate and ionizing radiation (IR). Pharmacological ascorbate has been shown to have tumor-specific toxic effects due to the formation of hydrogen peroxide. By catalyzing the oxidation of ascorbate, labile iron can enhance the rate of formation of hydrogen peroxide; labile iron can also react with hydrogen peroxide. Here we have investigated the magnitude of the labile iron pool in tumor and normal tissue. We also examined the ability of pharmacological ascorbate and IR to change the size of the labile iron pool. Although a significant amount of labile iron was seen in tumors (MIA PaCa-2 cells in athymic nude mice), higher levels were seen in murine tissues that were not susceptible to pharmacological ascorbate. Pharmacological ascorbate and irradiation were shown to increase the labile iron in tumor homogenates from this murine model of pancreatic cancer. As both IR and pharmacological ascorbate may rely on labile iron for their effects on tumor tissues, our data suggest that pharmacological ascorbate could be used as a radio-sensitizing agent for some radio-resistant tumors.

Renewed interest in using pharmacological ascorbate (AscH-) to treat cancer has prompted interest in leveraging its cytotoxic mechanism of action. A central feature of AscH- action in cancer cells is its ability to act as an electron donor to O2 for generating H2O2. We hypothesized that catalytic manganoporphyrins (MnP) would increase AscH- oxidation rates, thereby increasing H2O2 fluxes and cytotoxicity. Three different MnPs were tested (MnTBAP, MnT2EPyP, and MnT4MPyP), exhibiting a range of physicochemical and thermodynamic properties. Of the MnPs tested, MnT4MPyP exerted the greatest effect on increasing the rate of AscH- oxidation as determined by the concentration of ascorbate radical [Asc•-] and the rate of oxygen consumption. At concentrations that had minimal effects alone, combining MnPs and AscH- synergized to decrease clonogenic survival in human pancreatic cancer cells. This cytotoxic effect was reversed by catalase, but not superoxide dismutase, consistent with a mechanism mediated by H2O2. MnPs increased steady-state concentrations of Asc•- upon ex vivo addition to whole blood obtained either from mice infused with AscH- or patients treated with pharmacologic AscH-. Finally, tumor growth in vivo was inhibited more effectively by combining MnT4MPyP with AscH-. We concluded that MnPs increase the rate of oxidation of AscH- to leverage H2O2 flux and ascorbate-induced cytotoxicity.

Silicon photonic microring resonators have established their potential for label-free and low-cost biosensing applications. However, the long-term performance of this optical sensing platform requires robust surface modification and biofunctionalization. Herein, we demonstrate a conjugation strategy based on an organophosphonate surface coating and vinyl sulfone linker to biofunctionalize silicon resonators for biomolecular sensing. To validate this method, a series of glycans, including carbohydrates and glycoconjugates, were immobilized on divinyl sulfone (DVS)/organophosphonate-modified microrings and used to characterize carbohydrate-protein and norovirus particle interactions. This biofunctional platform was able to orthogonally detect multiple specific carbohydrate-protein interactions simultaneously. Additionally, the platform was capable of reproducible binding after multiple regenerations by high-salt, high-pH, or low-pH solutions and after 1 month storage in ambient conditions. This remarkable stability and durability of the organophosphonate immobilization strategy will facilitate the application of silicon microring resonators in various sensing conditions, prolong their lifetime, and minimize the cost for storage and delivery; these characteristics are requisite for developing biosensors for point-of-care and distributed diagnostics and other biomedical applications. In addition, the platform demonstrated its ability to characterize carbohydrate-mediated host-virus interactions, providing a facile method for discovering new antiviral agents to prevent infectious disease.

A 22-year-old female with no medical history presented to the emergency room with 2 weeks of rapidly worsening dyspnea on exertion, orthopnea, and cough. On cardiac auscultation, she was noted to have to-and-fro murmurs and a continuous murmur with signs of right heart failure. Echocardiographic images obtained showed moderate to severe aortic regurgitation, severe tricuspid regurgitation, and a "windsock" originating in the right coronary sinus of Valsalva and terminating in the right atrium. The aortic valve had four leaflets, with the right leaflet function compromised by the ruptured sinus, causing aortic regurgitation. The patient underwent resection of the sinus aneurysm and aortic valve replacement with a bioprosthetic valve. Quadricuspid aortic valves are uncommon and are rarely associated with sinus of Valsalva aneurysm. The prevalence in the general population, clinical progression, and prognosis of this unique congenital abnormality are reviewed., (© 2011 Copyright the Authors. Congenital Heart Disease © 2011 Wiley Periodicals, Inc.)

The multiple-locus variable-number tandem-repeats analysis (MLVA) method for genotyping has proven to be a fast and reliable typing tool in several bacterial species. MLVA is in our laboratory the routine typing method for Salmonella enterica subsp. enterica serovar Typhimurium, Escherichia coli (two assays), Listeria monocytogenes and Yersinia enterocolitica. The gram-negative invasive enteropathogenic bacterium Shigella is the most common cause of bacillary dysentery (shigellosis) worldwide, and is a global human health problem. It was of great interest to develop a rapid and robust MLVA-assay for this important pathogen. Though not common in Norway, we do receive isolates mostly associated with foreign travel and thus an outbreak may be possible. The resulting MLVA-assay is based on seven polymorphous VNTRs found by search in the published genomes of all Shigella species. The assay is fast (one multiplexed PCR reaction), robust and show high divergence among the Shigellae. A total of 235 Shigella spp. were typed with 194 distinct MLVA-genotypes. An outbreak cluster of Shigella sonnei was additionally identified during manuscript preparation., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Kapha is dominant and vitiated in Vasant ritu as it is described in Ayurveda. Acharya Chakrapani has said in chapter six, that not only Vaman, but all the five biopurification methods of the Panchakarma should be practiced in Vasant ritu. Out of the two best seasons in a year for purification, Vasant is better one. This pilot research study was carried out to see the effect of this biopurification process on different disorders. The results were marvelous, as symptomatically 58% relief was achieved.

We describe an 18 month old girl with acute hemorrhagic edema of infancy, with palpable erythemaous purpuric rash on face, upper and lower limbs and ear lobules associated with edema and leukocytoclastic vasculitis. There were no systemic complications.

Seckel syndrome is a rare genetic disorder with autosomal recessive inheritance. It is associated with many CNS anomalies along with involvement of other systems. We present a case of Seckel syndrome with semilobar holoprosencephaly as associated CNS anomaly, which to the best of our knowledge has not been reported earlier.

We have shown previously that wild-type p53 renders H460 human lung cancer cells more sensitive to apoptosis induction by environmental carcinogen benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), but the mechanism of cell death is not fully understood. The present study provides insights into the mechanism by which BPDE causes apoptosis in H460 cells. Exposure of H460 cells to BPDE resulted in a concentration-dependent apoptotic cell death characterized by cleavage of poly(ADP-ribose)polymerase, DNA condensation, and apoptotic histone-associated DNA fragments released into the cytosol. The BPDE-mediated release of apoptotic histone-associated DNA fragments into the cytosol was also observed in a normal bronchial epithelial cell line BEAS-2B. The BPDE-induced apoptosis in H460 cells correlated with up-regulation of pro-apoptotic protein Bak, downregulation of anti-apoptotic Bcl-2 family members Bcl-2 and Bcl-xL, release of cytochrome c from mitochondria to the cytosol without a change in mitochondrial membrane potential or mitochondrial morphology (electron microscopy), and cleavage of caspase-8, -9, and -3. Ectopic expression of Bcl-2 failed to confer significant protection against BPDE-induced apoptosis in H460 cells. The SV40 immortalized mouse embryonic fibroblasts (MEFs) derived from Bak and Bax double knockout mice, but not Bid knockout mice, were significantly more resistant to BPDE-induced apoptosis compared with the MEFs derived from wild-type mice. The BPDE-induced apoptosis was partially but statistically significantly attenuated in the presence of specific inhibitors of caspase-9 (z-LEHDfmk) and caspase-8 (z-IETDfmk). In conclusion, the present study reveals that BPDE-induced apoptosis in H460 cells is associated with Bak induction and caspase activation but independent of Bcl-2.

Albunex is an Food and Drug Administration-approved ultrasound contrast agent used for the enhancement of left ventricular endocardial borders. To determine the efficacy of intravenously administered Albunex with regard to left ventricular opacification (LVO), a retrospective analysis of 117 patients who received 202 injections of Albunex for enhancement of endocardial borders was done (dose 0.08 to 0.22 ml /kg). Patients were routinely referred to our echocardiography laboratory for stress echocardiography for standard indications. Optimized settings for contrast enhancement (3.5 MHz transducer frequency and maximum dynamic range) were used. Four observers graded LVO on a scale from 0 to 3 (0 = no Albunex seen in the ventricular cavity; 3 = Albunex densely seen in the ventricular cavity). Overall, LVO was reported in 166 (82%) of 202 injections or in 91 (78%) of 117 patients. A significant reduction in LVO was noted in patients with mitral regurgitation, tricuspid regurgitation, atrial fibrillation, systolic dysfunction, or pulmonary hypertension (increased pulmonary artery systemic pressure). LVO was seen in 88% of the patients without these conditions. However, only 12 (44%) of 27 patients with one or more of the above conditions had LVO (p < 0.05). LVO can be achieved in the majority of patients after intravenously administered Albunex when imaged with optimal transducer settings. A subset of patients with systolic dysfunction, mitral regurgitation, tricuspid regurgitation, atrial fibrillation, or increased pulmonary artery systemic pressure has less effective LVO with Albunex. Heart disease associated with decreased forward flow appears to be associated with diminished LVO.