Erythromelalgia. Part II: Differential diagnoses and management.

The management of erythromelalgia is challenging and requires multidisciplinary effort. Patient education is crucial as unsafe self-administered cooling techniques can lead to significant morbidity, including acral necrosis, infection, and amputation. The goal of management is pain control, reduction of flare frequency, and prevention of complications. This text is focused on the management of erythromelalgia and several other incompletely understood and under-recognized neurovascular disorders such as red scrotum syndrome, red ear syndrome, facial flushing, and complex regional pain syndrome.

Erythromelalgia. Part I: Pathogenesis, clinical features, evaluation, and complications.

Erythromelalgia is a rare pain disorder that is underrecognized and difficult-to-treat. It is characterized by episodes of extremity erythema and pain that can be disabling; it may be genetic, related to an underlying systemic disease, or idiopathic. Considering the prominent cutaneous features characteristic of the condition, dermatologists can play an important role in early recognition and limitation of morbidity. The first article in this 2-part continuing medical education series reviews the epidemiology, pathogenesis, clinical manifestations, evaluation, and complications.

Cutaneous tuberculosis. Part I: Pathogenesis, classification, and clinical features.

Tuberculosis is an ancient disease that continues to affect an estimated 10 million people per year and is responsible for 1.4 million deaths per year. Additionally, the HIV epidemic and multidrug resistance present challenges to disease control. Cutaneous tuberculosis is an uncommon, often indolent, manifestation of mycobacterial infection that has a varied presentation. Its diagnosis is challenging, as lesions mimic other, more common conditions and microbiological confirmation is often not possible. Cutaneous tuberculosis can be broadly categorized into multibacillary and paucibacillary forms. Approximately one-third of skin tuberculosis is associated with systemic involvement. By recognizing cutaneous tuberculosis early, dermatologists can play an important role in disease control. The first article in this 2-part continuing medical education series describes the latest epidemiology, microbiology, and pathogenesis of tuberculosis. Furthermore, we review the classification, clinical manifestations, common clinical differentials, and systemic involvement that occur in cutaneous tuberculosis.

Cutaneous tuberculosis. Part II: Complications, diagnostic workup, histopathologic features, and treatment.

Despite the availability of effective treatment regimens for cutaneous tuberculosis, challenges to disease control result from delayed diagnosis, infection with multidrug-resistant mycobacterial strains, and coinfection with HIV. Delayed diagnosis can be mitigated when dermatologists are sensitized to the clinical signs and symptoms of infection and by the incorporation of appropriate diagnostic tests. All cases of cutaneous tuberculosis should be confirmed with histopathology and culture with or without molecular testing. In each case, a thorough evaluation for systemic involvement is necessary. Mycobacteria may not be isolated from cutaneous tuberculosis lesions and therefore, a trial of antituberculosis treatment may be required to confirm the diagnosis. The second article in this 2-part continuing medical education series describes the sequelae, histopathology, and treatment of tuberculosis.

HPV-57 Verruca Vulgaris Mimicking Epidermodysplasia Verruciformis.

ABSTRACT: Human papilloma virus (HPV) is the causative agent for a variety of cutaneous lesions including verruca vulgaris (VV) and epidermodysplasia verruciformis (EDV). There are more than 200 known genotypes of HPV, and specific HPV types are associated with different clinical manifestations and malignant potentials. Herein, we describe a case of a 43-year-old immunocompetent woman who presented with morphologically distinct lesions that were most consistent with EDV on clinical examination. However, further histopathological and viral analysis confirmed the lesions as HPV-57-positive VV. The risk of malignant transformation, and therefore treatment and surveillance, is dramatically different in VV versus EDV. Therefore, this case highlights the importance of a proper histopathological diagnosis with HPV viral testing when clinical presentations may vary or mimic other diseases.

Design and Analysis of a Reconfigurable Gilbert Mixer for Software-Defined Radios.

A reconfigurable gm-boosted, image-rejected downconversion mixer is presented in this paper using the SiGe 8 HP technology. The proposed mixer operates within 0.9-13.5 GHz that is suitable for software-defined radio applications. The conversion mixer comprises of resistive biased radio frequency (RF) section, double balanced Gilbert cell mixer core sections divided as per I and Q stages for image-rejection purpose, inductively peaked gm-boosting section and tunable filter section, respectively. In comparison to previous works in the scientific literature, the design shows enhanced conversion gain (CG), noise figure (NF), and image-rejection ratio (IRR). For the entire band of operation, the mixer attains a good return loss |S11| of <-10 dB. Additionally, the design accomplishes an excellent CG of 22 dB, NF of 2.5 dB, and an image-rejection ratio of 30.2 dB at maximum frequency. Finally, a third-order intercept point (IP3) of -3.28 dBm and 1 dB compression point (CP1) of -13 dBm, respectively, shows moderate linearity performance.

Use of an oral stable isotope label to confirm variation in red blood cell mean age that influences HbA1c interpretation.

HbA1c is commonly used to monitor glycemic control. However, there is growing evidence that the relationship between HbA1c and mean blood glucose (MBG) is influenced by variation in red blood cell (RBC) lifespan in hematologically normal individuals. Correction of HbA1c for mean RBC age (MRBC ) requires a noninvasive, accurate, and affordable method to measure RBC survival. In this study, we evaluated whether a stable isotope approach would satisfy these requirements. RBC lifespan and MRBC were determined in a group of nine hematologically normal diabetic and nondiabetic subjects using oral (15) N-glycine to label heme in an age cohort of RBC. The MRBC was 58.7 ± 9.1 (2SD) days and RBC lifespan was 106 ± 21 (2SD) days. This degree of variation (±15-20%) is consistent with previous studies using other techniques. In a subset of seven subjects, MRBC determined with the biotin label technique were available from approximately five years prior, and strongly correlated with the stable isotope values (R(2) = 0.79). This study suggests that the MRBC is stable over time but varies substantially among individuals, and supports the importance of its variation in HbA1c interpretation. The characteristics of the stable isotope method support its suitability for studies to directly evaluate the impact of variation in MRBC on the interpretation of HbA1c.

Growth hormone therapy does not impact the development of intracranial hypertension in children with Chiari malformation.

OBJECTIVES: Patients with Chiari malformation (CM) are prone to a variety of neurological sequelae, including benign intracranial hypertension (BIH). In these patients, BIH is attributed to impaired cerebrospinal fluid (CSF) flow due to anatomical abnormalities of the posterior fossa. Occasionally, patients with CM may require growth hormone therapy (GHT), which can increase the production of CSF. It is thought that patients with CM who undergo GHT are at high risk of BIH-associated symptoms (BIHAS). We describe the incidence of neurological symptoms in 34 patients with CM before and during GHT. METHODS: The database of a pediatric endocrinology center was queried for patients with CM who received GHT from 2010-22. Records were reviewed for adverse events. Demographic and radiological data were collected and analyzed. Patients with neoplastic disease, active inflammation, or acute trauma were excluded. CM diagnoses were independently assigned by a neuroradiology department. Patients were grouped based on the presence and nature of symptoms before and during GHT. Relationships between starting dose/BMI and occurrence of BIHAS/all GHT-associated symptoms were evaluated. RESULTS: GHT was not associated with new-onset or worsening of preexisting BIHAS in 33 out of 34 patients with CM. Five complex patients continued to have preexisting BIHAS, which did not worsen. Of the four patients who developed new-onset BIHAS during GHT, three patients' symptoms were attributed to other medical conditions. No patient permanently discontinued GHT due to BIHAS. CONCLUSIONS: Growth hormone therapy is likely a safe treatment in patients with Chiari malformation and is unlikely to cause BIHAS.

Pediatric Endocrine Society Statement on Considerations for Use of Teplizumab (Tzield™) in Clinical Practice.

Teplizumab (TzieldTM, Provention Bio), a monoclonal antibody directed at T-cell marker CD3, is the first medication approved by the FDA to delay progression from stage 2 to stage 3 type 1 diabetes. To date, the overwhelming majority of pediatric endocrinologists do not have experience using immunotherapeutics and seek guidance on the use of teplizumab in clinical practice. To address this need, the Pediatric Endocrine Society (PES) Diabetes Special Interest Group (Diabetes SIG) and Drug and Therapeutics Committee assembled a task force to review clinical trial data and solicit expert recommendations on the approach to teplizumab infusions. We present considerations on all aspects of teplizumab administration, utilizing evidence where possible and providing a spectrum of expert opinions on unknown aspects. We discuss patient selection and prescreening, highlighting the safety and considerations for monitoring and treatment of side effects. We propose a schedule of events, a protocol for administration, and discuss practice management aspects. We advocate for the need for further long-term systematic surveillance studies to continue evaluating the efficacy and safety of teplizumab.

Precocious Puberty and GnRH analogs: Current treatment practices and perspectives amongst US pediatric endocrinologists.

INTRODUCTION: GnRHas are used for treatment of precocious puberty. Over the last decade, several new formulations have been approved. METHODS: The Drugs & Therapeutics subcommittee of the Pediatric Endocrine Society (PES) undertook a review to ascertain the current treatment options, prescribing behaviors, and practices of GnRHas among pediatric endocrinologists practicing within the United States. The survey consisted of four main subsections: 1. Description of clinical practice; 2. Self-assessment of knowledge base of pediatric and adult GnRHa formulations; 3. Current practice for treating CPP; and 4. Utilization of healthcare resources. RESULTS: There were 223 survey respondents. Pediatric endocrine practitioners were most familiar with the pediatric one-monthly preparation, the three-month preparation, and the histrelin implant (Supprelin®) (61.9%, 71.7%, and 34.5%, respectively), with lower familiarity for 24-week triptorelin intramuscular (Triptodur®) and 22.9% and six-month subcutaneous leuprolide (Fensolvi®). Only 23% of the respondents reported being extremely familiar with the availability of adult formulations, and 25% reported being completely unaware of cost differences between pediatric and adult GnRHa preparations. The implant was the most preferred therapy (44.4%), but in practice, respondents reported a higher percentage of patients were treated with 3-month preparation. While family preference/ease of treatment (87%) was the key determinant for using a particular GnRHa preparation, insurance coverage also played a significant role in the decision (65.5%). Responses regarding assessment for efficacy of treatment were inconsistent, as were practices and criteria for obtaining an MRI. CONCLUSIONS: The survey indicated there is more familiarity with older, shorter-acting GnRHas, which are prescribed in greater numbers than newer, longer-acting formulations. There is lack of consensus on the need for CNS imaging in girls presenting with CPP between 6-8 years of age and use of laboratory testing to monitor response to treatment. Insurance requirements regarding CNS imaging and laboratory monitoring are highly variable. Despite having similar constituents and bioavailability there are substantial cost differences between the pediatric and adult formulations and lack of evidence for safe use of these formulations in children. The survey-based analysis highlights the challenges faced by prescribers, while reflecting on areas where further research is needed to provide evidence-based practice guidelines for pediatric endocrinologists.

Value of 1-Hour Plasma Glucose During an Oral Glucose Tolerance Test in a Multiethnic Cohort of Obese Children and Adolescents.

One hour plasma glucose (1-hr PG) concentration during an oral glucose tolerance test (OGTT) is steadily emerging as an independent predictor of type 2 diabetes (T2D). Methods: We applied the current cut off thresholds reported in the pediatric literature for the 1-hr PG, 132.5 (7.4 mmol/l) and 155 mg/dL (8.6 mmol/l) during an OGTT, to report abnormal glucose tolerance (AGT) using ROC curve analyses. We determined the empirical optimal cut point for 1-hr PG for our multi ethnic cohort using the Youden Index. Results: About 1-hour and 2-hours plasma glucose showed the highest predictive potential based on Areas under the curve (AUC) values of 0.91 [CI: 0.85, 0.97] and 1 [CI: 1, 1], respectively. Further comparison of the ROC curves of the 1-hour and 2-hour PG measurements as predictors of an abnormal OGTT showed that their associated AUCs differed significantly (X2(1) = 9.25, P < .05). Using 132.5 mg/dL as the cutoff point for plasma glucose at 1-hour yielded a ROC curve with an AUC of 0.796, a sensitivity of 88%, and a specificity of 71.2%. Alternatively, the cutoff point of 155 mg/dL resulted in a ROC AUC of 0.852, a sensitivity of 80%, and a specificity of 90.4%. Conclusion: Our cross-sectional study affirms that the 1-hr PG can identify obese children and adolescents at increased risk for prediabetes and/or T2D with almost the same accuracy as a 2-hr PG. In our multi-ethnic cohort, a 1-hr PG ⩾ 155 mg/dL (8.6 mmol/l) serves as an optimal cut-point, using the estimation of the Youden index with AUC of 0.86 and sensitivity of 80%.We support the petition to consider the 1-hr PG as integral during an OGTT, as this adds value to the interpretation of the OGTT beyond the fasting and 2-hr PG.

A simple and straightforward strategy for expedient access to benzoxazoles using chemically engineered 2D magnetic graphene oxide nanosheets as an eco-compatible catalyst.

Two-dimensional (2D) graphene oxide nanosheets serve as an excellent support material for immobilizing metal complexes to deal with the drawbacks of homogeneous catalysis. In this work, we report a magnetically retrievable graphene oxide (MGO) based copper nanocatalytic system that has been efficiently exploited for obtaining a series of pharmaceutically and biologically active benzoxazole scaffolds. The nanocatalyst was designed by covalent immobilization of dehydroacetic acid (DHA) onto a magnetic amino-silanized graphene oxide nanosupport which was accompanied by its metallation with copper acetate. The structure of the synthesized MGO hybrid material (Cu@DHA@APTES@MGO) was characterized by numerous physico-chemical techniques such as transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), vibrating sample magnetometry (VSM), elemental mapping, atomic absorption spectroscopy (AAS), thermogravimetric analysis (TGA), Brunauer-Emmett-Teller (BET) surface area analysis and energy-dispersive X-ray fluorescence spectroscopy (ED-XRF). The fabricated architectures exhibited high efficiency for cyclization of 2-aminophenols and ß-diketones with wide substrate scope, excellent functional group tolerance, a higher conversion percentage (>98%) and a high turnover number (TON). The exceptional catalytic activity could be attributed to the 2D architecture of graphene oxide which provides space for trapping of reactants between 2D graphitic overlayers and metal surfaces and the reaction proceeds to afford benzoxazole products with moderate to excellent conversion percentages. Notably, this nanocomposite could be recovered easily through an external magnetic force and reused for multiple runs without any appreciable loss in its catalytic efficacy.

The evolution of pituitary cysts in growth hormone-treated children.

OBJECTIVES: We have previously shown that pituitary cysts may affect growth hormone secretion. This study sought to determine cyst evolution during growth hormone treatment in children. METHODS: Forty-nine patients with short stature, a pituitary cyst, and at least two brain MRI scans were included. The percent of the pituitary gland occupied by the cyst (POGO) was calculated, and a cyst with a POGO of ≤15% was considered small, while a POGO >15% was considered large. RESULTS: Thirty-five cysts were small, and 14 were large. Five of the 35 small cysts grew into large cysts, while 6 of the 14 large cysts shrunk into small cysts. Of 4 cysts that fluctuated between large and small, 3 presented as large and 1 as small. Small cysts experienced greater change in cyst volume (CV) (mean=61.5%) than large cysts (mean=-0.4%). However, large cysts had a greater net change in CV (mean=44.2 mm3) than small cysts (mean=21.0 mm3). Older patients had significantly larger mean pituitary volume than younger patients (435.4 mm3 vs. 317.9 mm3) and significantly larger mean CV than younger patients (77.4 mm3 vs. 45.2 mm3), but there was no significant difference in POGO between groups. CONCLUSIONS: Pituitary cyst size can vary greatly over time. Determination of POGO over time is a useful marker for determining the possibility of a pathologic effect on pituitary function since it factors both cyst and gland volume. Large cysts should be monitored closely, given their extreme, erratic behavior.

Functional profile and encapsulating properties of Colocasia esculenta (Taro).

Especially in tropical and subtropical countries, tuber and root crops have developed into important food crops. Due to its use in food preparation, aesthetics, and medicine, taro (Colocasia esculenta) is ranked as the fifth most important root crop. In comparison, it stores a considerable quantity of starch - even more than potatoes, sweet potatoes, cassava, and other similar crops. Colocasia leaves are lower in calories and high in dietary fiber minerals and proteins. The corms of Colocasia antiquorum contain anthocyanins such as pelargonidin-3-glucoside, cyanidin-3-glucoside, and cyanidin-3-chemnoside, which are reported to possess antifungal and antioxidative characteristics. The underground corms of taro (Colocasia esculenta), which contain 70%-80% starch, are the primary reason for its cultivation. Taro is a highly digestible root vegetable with a high content of mucilaginous gums and trivial starchy granules. It is used to make a variety of dishes. This review article highlights the functional properties, phytochemical profile, encapsulating properties, and various industrial applications. Its health advantages and dietary uses were also addressed.

Vegetable proteins as encapsulating agents: Recent updates and future perspectives.

The use of proteinaceous material is desired as it forms a protective gelation around the active core, making it safe through temperature, pH, and O2 in the stomach and intestinal environment. During the boom of functional food utilization in this era of advancement in drug delivery systems, there is a dire need to find more protein sources that could be explored for the potential of being used as encapsulation materials, especially vegetable proteins. This review covers certain examples which need to be explored to form an encapsulation coating material, including soybeans (conglycinin and glycinin), peas (vicilin and convicilin), sunflower (helianthins and albumins), legumes (glutenins and albumins), and proteins from oats, rice, and wheat. This review covers recent interventions exploring the mentioned vegetable protein encapsulation and imminent projections in the shifting paradigm from conventional process to environmentally friendly green process technologies and the sensitivity of methods used for encapsulation. Vegetable proteins are easily biodegradable and so are the procedures of spray drying and coacervation, which have been discussed to prepare the desired encapsulated functional food. Coacervation processes are yet more promising in the case of particle size formation ranging from nano to several hundred microns. The present review emphasizes the significance of using vegetable proteins as capsule material, as well as the specificity of encapsulation methods in relation to vegetable protein sensitivity and the purpose of encapsulation accompanying recent interventions.

Practice Variation among Pediatric Endocrinologists in the Dosing of Glucocorticoids in Young Children with Congenital Adrenal Hyperplasia.

A Pediatric Endocrine Society (PES) Drugs and Therapeutics Committee workgroup sought to determine the prescribing practices of pediatric endocrinologists when treating children <10 years of age with congenital adrenal hyperplasia (CAH). Our workgroup administered a 32-question online survey to PES members. There were 187 respondents (88.9% attending physicians), mostly from university-affiliated clinics (~80%). Ninety-eight percent of respondents prescribed the short-acting glucocorticoid hydrocortisone to treat young children, as per the Endocrine Society CAH Guidelines, although respondents also prescribed long-acting glucocorticoids such as prednisolone suspension (12%), prednisone tablets (9%), and prednisone suspension (6%). Ninety-seven percent of respondents indicated that they were likely/very likely to prescribe hydrocortisone in a thrice-daily regimen, as per CAH Guidelines, although 19% were also likely to follow a twice-daily regimen. To achieve smaller doses, using a pill-cutter was the most frequent method recommended by providers to manipulate tablets (87.2%), followed by dissolving tablets in water (25.7%) to create a daily batch (43.7%) and/or dissolving a tablet for each dose (64.6%). Thirty-one percent of providers use pharmacy-compounded hydrocortisone suspension to achieve doses of <2.5 mg. Our survey shows that practices among providers in the dosing of young children with CAH vary greatly and sometimes fall outside of the CAH Guidelines-specifically when attempting to deliver lower, age-appropriate hydrocortisone doses.