A Case Report on an Unusual Presentation of Pernicious Anemia.

Pernicious anemia is an autoimmune disease leading to impaired absorption of dietary cobalamin. Patients with pernicious anemia can present with multiple hematological, neurological and gastrointestinal complaints. Herein, we have a case of pernicious anemia presenting with alternating bowel habit. This was challenging and unique as the patient didn't have any usual condition responsible for alternating bowel habit and it is not reported in cases of pernicious anemia either. The case is a 46-year-old male who was admitted with alternating bowel habit, paresthesia and fever for the last 6 months. Patient was found to be severely anemic. After full workup, he was diagnosed with pernicious anemia. The patient was treated with IM Injections of Vitamin B12. After 3 months of discharge, the patient was free of all the symptoms. This case emphasizes the importance of investigating anemic patients with alternating bowel habit for pernicious anemia and also the need to exclude other causes of this symptom before labeling it as pernicious anemia only.

Accuracy of Multimodality Fetal Imaging (US, MRI, and CT) for Congenital Musculoskeletal Anomalies.

BACKGROUND: Ultrasonography (US) is the first-line diagnostic tool used to assess fetal musculoskeletal (MSK) anomalies. Associated anomalies in other organ systems may benefit from evaluation via Magnetic Resonance Imaging (MRI). In this study, we compared the diagnostic accuracy of US and MRI to diagnose fetal MSK (primary objective) and non-MSK anomalies (secondary objective). We describe additional findings by low-dose computerized tomography (CT) in two cases incompletely characterized via US and MRI. MATERIALS AND METHODS: This was an IRB-approved retrospective study of consecutive patients with suspected fetal MSK anomalies examined between December 2015 and June 2020. We compared individual MSK and non-MSK anomalies identified via US, MRI, and CT with postnatal outcomes. Sensitivity and specificity for US and MRI were calculated and compared. RESULTS: A total of 31 patients with 112 MSK and 43 non-MSK anomalies were included. The sensitivity of MRI and US for MSK anomalies was not significantly different (76.6% vs. 61.3%, p = 0.3). Low-dose CT identified eight additional skeletal anomalies. MRI diagnosed a higher number of non-MSK anomalies compared to US (81.4% vs. 37.2%, p < 0.05). CONCLUSIONS: Fetal MRI and US have comparable sensitivity for MSK anomalies. In selected cases, low-dose CT may provide additional information. Fetal MRI detected a larger number of non-MSK anomalies in other organ systems compared to US. Multimodality imaging combining all the information provided by MRI, US, and CT, if necessary, ultimately achieved a sensitivity of 89.2% (95% CI: 83.4% to 95.0%) for the diagnosis of musculoskeletal anomalies and 81.4% for additional anomalies in other organs and systems.

The modified Kocher criteria for septic hip: Does it apply to the knee?

Background: Pediatric septic arthritis is a surgical emergency and timely diagnosis prevents serious complications. To differentiate between septic hip and transient synovitis, the predictive value of four original Kocher criteria (fever, inability to bear weight, elevated serum white blood cell count, and elevated erythrocyte sedimentation rate) plus Caird's addition of elevated C-reactive protein have been studied, termed the modified Kocher criteria. These criteria have not been tested extensively on septic knee. This study tested the utility of the modified Kocher criteria in predicting septic knee while validating it for septic hip. Methods: A retrospective chart review was conducted of pediatric patients evaluated at a single institution for irritable hip or knee between 2009 and 2018. Patients who underwent arthrocentesis were included and the modified Kocher criteria were applied to all. Results: One hundred fifty-five patients (96 hips and 59 knees) were identified. One hundred four (67.1%) patients had septic arthritis with 44/59 (74.6%) of knees and 60/96 (62.5%) of hips. The strongest predictors for septic hip and knee were elevated C-reactive protein (odds ratio = 26.9, p < 0.0001) and refusal to bear weight (odds ratio = 14.5, p < 0.0001), respectively. For hips, 5/5 criteria produced a 100% positive predictive value for septic arthritis. For knees, the combination of inability to bear weight and elevated C-reactive protein had a positive predictive value of 89.7%. Conclusion: While all five of the modified Kocher criteria are not predictive of pediatric septic knee, the combination of two specific factors (inability to bear weight and elevated C-reactive protein) is strongly predictive. This study validates previous work that the modified Kocher criteria are predictive of septic hip. Level of evidence: level III.

Spondyloepiphyseal dysplasia congenita: Use of complementary 3D reconstruction imaging for preoperative planning.

We present a case of spondyloepiphyseal dysplasia congenita (SEDC), a rare autosomal dominant genetic disorder that results in short stature and skeletal anomalies. Children with SEDC have disproportionate short-trunked short stature, platyspondyly, coxa vara, and epiphyseal involvement. Those with coxa vara can develop osteoarthritis of the hip early and a valgus hip osteotomy is recommended to preserve hip function and delay progression to osteoarthritis. Surgery is difficult due to the three-dimensional deformity, unossified femoral head, and small patient size. In this case, a patient-specific surgical plan and implant sizing was developed using a composite 3D reconstruction from computed tomography (CT) and magnetic resonance imaging (MRI). The complementary use of both modalities allowed for a complete visualization of the patient's dysplastic femoral head & neck anatomy.

Assessment of Prescribing Pattern and Safety Profile of Drugs Used in Intranasal Route in Paediatric Age Group of Patients in a Tertiary Care Hospital.

Background Recently there has been an increased preference for intranasal delivery of drugs due to highly vascular nasal mucosa, bypassing first pass metabolism and the blood brain barrier (BBB) lead in quick drug absorption to the systemic circulation and direct access to brain from olfactory region. For pediatric patients this route offers significant benefits over injections or oral routes, like increased compliance, easy administration, and minimal side effects. Objective Assessment of prescription pattern of drugs and safety profile of drugs used by intranasal route in paediatric age group. Method Our study was a prospective observational study paediatric age group of patients conducted in the departments of Pharmacology, Paediatrics and Otorhinolaryngology of Burdwan Medical College and Hospital, Burdwan. Data were collected in CRF and frequency distribution of collected data done. Microsoft Excel 2010 was used for analysis. Result Common age group was infants. Males were more in number. Most common indication was epistaxis. Intranasal drugs per prescription were 1.05. Most commonly prescribed intranasal drug was nasal saline. Nasal decongestant was the most common prescribed medication. Nasal drops were the most common dose formulation. Conclusion Intranasal drug prescribing in our study was mainly aimed for treating local problems, very few being for systemic action. Some prescribing indicators like prescribing by generic name and prescribing from national essential drug lists were acceptable with scope for improvement. Average number of drugs per prescription and antibiotic use was high. Adverse events after intranasal drug use were primarily local and nose related.

Diversity and Inclusion in an Orthopaedic Surgical Society: A Longitudinal Study.

BACKGROUND: Diversity and inclusion are critical to providing the best possible health care. Previous studies have shown that diversity among physicians increases cultural competency, which in turn enhances the quality of care provided and increases minoritized patients' participation in decisions regarding their health care. However, physician diversity in both race and sex is lacking in orthopaedic surgery. This study seeks to determine the sex and racial diversity in the membership and leadership of the Pediatric Orthopaedic Society of North America (POSNA). METHODS: POSNA membership and leadership were reviewed for the years 2010, 2015, and 2020. This data was gathered from membership directories and committee reference books. All North American Active Members' race/ethnicity and sex were recorded for each year. The categories for race/ethnicity are Caucasian, East/South/Middle Eastern Asian American (Asian), Hispanic/Latin/South American (HLSA), and African American. RESULTS: From 2010 to 2020, Active Members of POSNA increased from 608 to 818, and the percentage of female (14.6% to 23.7%), Asian (7.4% to 11.2%), HLSA (2.5% to 2.9%), and African American membership (1.6% to 1.8%) increased. Male (85.4% to 76.3%) and Caucasian (88.5% to 84.0%) membership decreased. From 2010 to 2020, male leadership decreased on both the Board of Directors and Committee Chairs (89.5% to 81.8% and 86.4% to 64.7%, respectively), as did Caucasians (94.7% to 81.8% and 90.9% to 88.2%, respectively). The number of Asian members holding positions on both the Board of Directors and Committee Chairs increased (0% to 18.2% and 4.5% to 11.8%, respectively) as did the number of females (10.5% to 18.2% and 13.6% to 35.3%, respectively). HLSA and African American members were proportionally represented in leadership for the years 2010 and 2015. CONCLUSIONS: Membership in POSNA has increased between 2010 to 2020 for every diversity category examined and POSNA membership exhibits significantly more diversity than the orthopaedic specialty as a whole. Leadership as a whole is more diverse in 2020 than it was in 2010. LEVEL OF EVIDENCE: Level II-retrospective.

Prenatal diagnosis of Sprengel's deformity in a patient with Klippel-Feil Syndrome.

We present a case of Klippel-Feil Syndrome, a congenital skeletal defect where multiple cervical vertebral bodies are fused. Klippel-Feil Syndrome has multiple associated anomalies, with a notable one being Sprengel's deformity. In this case, the patient was given a diagnosis of Klippel-Feil Syndrome prenatally after suspected cervical vertebrae fusion and Sprengel's deformity were seen on both fetal magnetic resonance imaging (MRI) and ultrasound. Prenatal diagnosis of Sprengel's deformity has been reported once in the literature. In this report, we present imaging findings of Sprengel's deformity seen in association with Klippel-Feil Syndrome using a combination of fetal ultrasound and MRI.

Is 70 the new 50? Complications and outcomes of transjugular intrahepatic portosystemic shunt in older versus younger patients.

BACKGROUND: An increased risk of complications of TIPS in patients older than 65 years of age has been described, but data is limited. The objective of this study was to determine if the rate of complications post-TIPS differs in patients 65 or younger, compared to those older than 65 years of age. METHODS: A retrospective chart review was performed for all patients who underwent TIPS procedure at Banner-University Medical Center Phoenix, from 2010 to 2018, specifically focusing on complications and outcomes post-TIPS. In total, 402 patients were included in this analysis. Complications included portosystemic encephalopathy, post-TIPS infection, acute kidney injury requiring hemodialysis, hemorrhage, respiratory complications, need for transplant, or death. RESULTS: A total of 402 patients were included and divided into two groups: 300 (74.6%) were 65 years or younger (ages 53 ± 9), and 102 were older than 65 years (70 ± 5 (p < 0.001)). There were no statistically significant differences between age groups when comparing portosystemic encephalopathy, post-TIPS infection, acute kidney injury, respiratory complications, need for transplant, or death. CONCLUSION: In this large, single-center cohort, there was no statistically significant difference in the rate of complications of TIPS between the two age groups. Based on our results, TIPS procedure is an equally safe option for properly selected patients with complications of portal hypertension, regardless of age.

Hypochondrogenesis: A pictorial assay combining ultrasound, MRI and low-dose computerized tomography.

We present a case of hypochondrogenesis, a rare autosomal dominant skeletal dysplasia that often results in infant death shortly after birth. Hypochondrogenesis can present similarly to other skeletal dysplasia diseases, notably achondrogenesis type II. The diagnosis of hypochondrogenesis was given during the prenatal stage after fetal imaging was performed using ultrasound, magnetic resonance imaging (MRI), and low-dose computerized tomography (CT). To the best of our knowledge, this is the first known case that reported the use of low-dose CT to assist in the prenatal diagnosis of hypochondrogenesis.

An Open Label Prospective Study on Evaluation of Safety and Efficacy of Cilnidipine Over Amlodipine in Stage 1 Hypertensive Patients.

Background Calcium channel blockers are considered the first line drug over renin-angiotensinaldosterone system inhibitor in black population and with renin-angiotensinaldosterone system inhibitor in non-black population with Hypertension. Amlodipine has longer biological half life and lower potential to stimulate SNS. But, is associated with reflex tachycardia and pedal oedema. Cilnidipine has potent inhibitory both on voltage gated L-type and N-type calcium channels with better anti-proteinuric effect and good tolerability. Hence, our study compared the efficacy, safety and compliance of cilnidipine over amlodipine in Stage 1 hypertensive subjects. Objective To find out antihypertensive and renoprotective effect of cilnidipine. Method The study was open-label, single centre, prospective, parallel design, randomized controlled was done in Outdoor Patient Department (OPD) of Medicine and Department of Pharmacology in Burdwan Medical College and Hospital (BMCH). Patients with stage 1 HTN received cilnidipine while the other group received amlodipine. There were 4 follow-up visits for each participant consisting of baseline, 1 week, 6 weeks and after 12 weeks. Clinical parameters including pulse rate, blood pressure and ankle oedema noted also laboratory investigations were done. Safety parameters with adverse events and compliance by traditional pill count method. Result Blood pressure was effectively decreased by both amlodipine and cilnidipine. Cilnidipine significantly decreased Pulse Rate while amlodipine increased it and the difference in Pulse Rate comparing both the groups was statistically significant. None of the ADRs were statistically significant except pedal oedema. Pedal oedema was noted only in amlodipine arm and was statistically significant. Compliance to both the drugs was excellent. Total cost of therapy was higher with cilnidipine. Conclusion Though amlodipine is preferred drug, cilnidipine should be a better alternative when we consider subjects with sympathetic over activity, proteinuria or pedal oedema.

Role of selenium addition to CdZnTe matrix for room-temperature radiation detector applications.

Because of its ideal band gap, high density and high electron mobility-lifetime product, cadmium zinc telluride (CdZnTe or CZT) is currently the best room-temperature compound-semiconductor X- and gamma-ray detector material. However, because of its innate poor thermo-physical properties and above unity segregation coefficient for Zn, the wide spread deployment of this material in large-volume CZT detectors is still limited by the high production cost. The underlying reason for the low yield of high-quality material is that CZT suffers from three major detrimental defects: compositional inhomogeneity, high concentrations of dislocation walls/sub-grain boundary networks and high concentrations of Te inclusions/precipitates. To mitigate all these disadvantages, we report for the first time the effects of the addition of selenium to the CZT matrix. The addition of Se was found to be very effective in arresting the formation of sub-grain boundaries and its networks, significantly reducing Zn segregation, improving compositional homogeneity and resulting in much lower concentrations of Te inclusions/precipitates. Growth of the new quaternary crystal Cd1-xZnxTe1-ySey (CZTS) by the Traveling Heater Method (THM) is reported in this paper. We have demonstrated the production of much higher yield according to its compositional homogeneity, with substantially lower sub-grain boundaries and their network, and a lower concentration of Te inclusions/precipitates.

Total Colonic Duplication Associated With Anorectal Malformation in a Male Boy.

Complete colorectal tubular duplication is very rare congenital anomaly and its association with anorectal malformation is extremely rare. Preoperative diagnosis is very difficult and management is also challenging. We report a case of a newborn present as a bucket handle variety of anorectal malformation which was per-operatively diagnosed as an ARM with rectal duplication. At his 14th months of age on laparotomy patient was diagnosed as a case of ARM with total colonic duplication with single appendix. We managed the case successfully without extensive bowel resection in staged procedure.

Metabolic Profiling of Intact Arabidopsis thaliana Leaves during Circadian Cycle Using 1H High Resolution Magic Angle Spinning NMR.

Arabidopsis thaliana is the most widely used model organism for research in plant biology. While significant advances in understanding plant growth and development have been made by focusing on the molecular genetics of Arabidopsis, extracting and understanding the functional framework of metabolism is challenging, both from a technical perspective due to losses and modification during extraction of metabolites from the leaves, and from the biological perspective, due to random variation obscuring how well the function is performed. The purpose of this work is to establish the in vivo metabolic profile directly from the Arabidopsis thaliana leaves without metabolite extraction, to reduce the complexity of the results by multivariate analysis, and to unravel the mitigation of cellular complexity by predominant functional periodicity. To achieve this, we use the circadian cycle that strongly influences metabolic and physiological processes and exerts control over the photosynthetic machinery. High resolution-magic angle spinning nuclear magnetic resonance (HR-MAS NMR) was applied to obtain the metabolic profile directly from intact Arabidopsis leaves. Combining one- and two-dimensional 1H HR-MAS NMR allowed the identification of several metabolites including sugars and amino acids in intact leaves. Multivariate analysis on HR-MAS NMR spectra of leaves throughout the circadian cycle revealed modules of primary metabolites with significant and consistent variations of their molecular components at different time points of the circadian cycle. Since robust photosynthetic performance in plants relies on the functional periodicity of the circadian rhythm, our results show that HR-MAS NMR promises to be an important non-invasive method that can be used for metabolomics of the Arabidopsis thaliana mutants with altered physiology and photosynthetic efficiency.

Stability of the Baseline Holder in Readout Circuits For Radiation Detectors.

Baseline holder (BLH) circuits are used widely to stabilize the analog output of application-specific integrated circuits (ASICs) for high-count-rate applications. The careful design of BLH circuits is vital to the overall stability of the analog-signal-processing chain in ASICs. Recently, we observed self-triggered fluctuations in an ASIC in which the shaping circuits have a BLH circuit in the feedback loop. In fact, further investigations showed that methods of enhancing small-signal stabilities cause an even worse situation. To resolve this problem, we used large-signal analyses to study the circuit's stability. We found that a relatively small gain for the error amplifier and a small current in the non-linear stage of the BLH are required to enhance stability in large-signal analysis, which will compromise the properties of the BLH. These findings were verified by SPICE simulations. In this paper, we present our detailed analysis of the BLH circuits, and propose an improved version of them that have only minimal self-triggered fluctuations. We summarize the design considerations both for the stability and the properties of the BLH circuits.

Novel ZnO:Al contacts to CdZnTe for X- and gamma-ray detectors.

CdZnTe (CZT) has made a significant impact as a material for room-temperature nuclear-radiation detectors due to its potential impact in applications related to nonproliferation, homeland security, medical imaging, and gamma-ray telescopes. In all such applications, common metals, such as gold, platinum and indium, have been used as electrodes for fabricating the detectors. Because of the large mismatch in the thermal-expansion coefficient between the metal contacts and CZT, the contacts can undergo stress and mechanical degradation, which is the main cause for device instability over the long term. Here, we report for the first time on our use of Al-doped ZnO as the preferred electrode for such detectors. The material was selected because of its better contact properties compared to those of the metals commonly used today. Comparisons were conducted for the detector properties using different contacts, and improvements in the performances of ZnO:Al-coated detectors are described in this paper. These studies show that Al:ZnO contacts to CZT radiation detectors offer the potential of becoming a transformative replacement for the common metallic contacts due to the dramatic improvements in the performance of detectors and improved long-term stability.

Microglia-derived HIV Nef+ exosome impairment of the blood-brain barrier is treatable by nanomedicine-based delivery of Nef peptides.

The negative factor (Nef) of human immunodeficiency virus (HIV) is an accessory protein that is thought to be integral to HIV-associated immune- and neuroimmune pathogenesis. Here, we show that nef-transfected microglia-released Nef+ exosome (exNef) disrupts the apical blood-brain barrier (BBB) and that only nef-transfected microglia release Nef in exosomes. nef-gfp-transduced neurons and astrocytes release exosomes but did not release exNef in the extracellular space. Apical administration of exNef derived from nef-transfected 293T cells reduced transendothelial electrical resistance (TEER) and increased permeability of the BBB. Microglia-derived exNef applied to either the apical/basal BBB significantly reduced expression of the tight junction protein, ZO-1, suggesting a mechanism of exNef-mediated neuropathogenesis. Microglia exposed to exNef release elevated levels of Toll-like receptor-induced cytokines and chemokines IL-12, IL-8, IL-6, RANTES, and IL-17A. Magnetic nanoparticle delivery of Nef peptides containing the Nef myrisolation site across an in vitro BBB ultimately reduced nef-transfected microglia release of Nef exosomes and prevented the loss of BBB integrity and permeability as measured by TEER and dextran-FITC transport studies, respectively. Overall, we show that exNef is released from nef-gfp-transfected microglia; exNef disrupts integrity and permeability, and tight junctions of the BBB, and induces microglial cytokine/chemokine secretion. These exNef-mediated effects were significantly restricted by Nef peptides. Taken together, this study provides preliminary evidence of the role of exNef in HIV neuroimmune pathogenesis and the feasibility of a nanomedicine-based therapeutics targeting exNef to treat HIV-associated neuropathogenesis.

Pediatric tuberculosis drug market: an insider perspective on challenges and solutions.

Representative stakeholders were consulted on how they felt access to pediatric tuberculosis (TB) drugs could be improved. A key recommendation is the development of new child-friendly, adequately dosed formulations with a good shelf life in all climate zones. There is also an urgent need to improve the diagnosis and reporting of children with TB. Manufacturers of pediatric TB medications are to be incentivized through improved coordination among all stakeholders, with streamlined regulatory approvals and increased consumer education on drug and regimen guidelines. Finally, pooled procurement is advised to ensure sustained market supply against affordable prices.

An array of virtual Frisch-grid CdZnTe detectors and a front-end application-specific integrated circuit for large-area position-sensitive gamma-ray cameras.

We developed a robust and low-cost array of virtual Frisch-grid CdZnTe detectors coupled to a front-end readout application-specific integrated circuit (ASIC) for spectroscopy and imaging of gamma rays. The array operates as a self-reliant detector module. It is comprised of 36 close-packed 6 × 6 × 15 mm(3) detectors grouped into 3 × 3 sub-arrays of 2 × 2 detectors with the common cathodes. The front-end analog ASIC accommodates up to 36 anode and 9 cathode inputs. Several detector modules can be integrated into a single- or multi-layer unit operating as a Compton or a coded-aperture camera. We present the results from testing two fully assembled modules and readout electronics. The further enhancement of the arrays' performance and reduction of their cost are possible by using position-sensitive virtual Frisch-grid detectors, which allow for accurate corrections of the response of material non-uniformities caused by crystal defects.

Test of a 32-channel Prototype ASIC for Photon Counting Application.

A new low-power application-specific integrated circuit (ASIC) for Cadmium Zinc Telluride (CZT) detectors for single-photon emission computed tomography (SPECT) application is being developed at BNL. As the first step, a 32-channel prototype ASIC was designed and tested recently. Each channel has a preamplifier followed by CR-RC3 shaping circuits and three independent energy bins with comparators and 16-bit counters. The ASIC was fabricated with TSMC 0.35-µm complementary metal-oxide-semiconductor (CMOS) process and tested in laboratories. The power consumption is around 1 mW/ch with a 2.5-V supply. With a gain of 400 mV/fC and the peaking time of 500 ns, the equivalent noise charge (ENC) of 360 e- has been measured in room temperature while the crosstalk rate is less than 0.3%. The 10-bit DACs for global thresholds have an integral nonlinearity (INL) less than 0.56% and differential nonlinearity (DNL) less than 0.33%. In the presentation, we will report the detailed test results with this ASIC.

Has Oxidative Stress any Role on Mechanisms of Aminophylline-Induced Seizures? An Animal Study.

BACKGROUND: Aminophylline can trigger seizures in patients without known underlying epilepsy or added risk factor for seizure exacerbation in epilepsy. Most of these seizures are difficult to control and are underappreciated compared to other drug toxicities. Despite a long clinical history of aminophylline-induced seizures, relatively little is known about the underlying molecular mechanisms that contribute to methylxanthine-induced seizure generation. OBJECTIVE: The present study evaluated the possible involvement of free radicals in aminophylline induced seizures in rat. METHOD: The rats were divided into two groups. The first group graded single doses of aminophylline from 100 to 300 mg/kg were administered intraperitoneally. On the basis of the results Aminophylline, a dose (300 mg/kg) producing tonic-clonic seizures and mortality in 100% animals was selected as control in the study. The second group were subjected to single antioxidant (Vitamin E or Vitamin C) or in combination for 45 days then single doses of aminophylline 300 mg/kg administered intraperitoneally to rats. RESULT: Aminophylline induced convulsions in rats in a dose-dependent manner, and both incidence of seizure and mortality were maximum at 300 mg/kg and there was significant increase of free radical generation. But though pre-treatment with antioxidants showed differential attenuating effects on aminophylline induced free radical generation as we all known but they were very much ineffective in antagonizing aminophylline induced seizures and post-seizure mortality by any appreciable extent. CONCLUSION: Though Aminophylline induces oxidative stress the results are suggestive that at least free radicals is not only cause of convulsiogenic effects and post-seizure mortality of aminophylline.