Diagnostic challenges of long COVID in children: a survey of pediatric health care providers' preferences and practices.

Introduction: Given the challenges in diagnosing children with long COVID, we sought to explore diagnostic practices and preferences among clinicians.

Methods: A ten-question survey assessed pediatric providers' clinical decision making for identifying and evaluating long COVID in children. Of the 120 survey respondents, 84 (70%) were physicians, 31 (26%) nurse practitioners, and 5 (4%) physician assistants.

Monocyte Anisocytosis is Associated with Sepsis in Children with Suspected Infection.

Background: Early, accurate determination of disease severity in an emergency setting is paramount for improving patient outcomes and healthcare costs. Monocyte anisocytosis, quantified as monocyte distribution width (MDW), has been shown to correspond with immune dysregulation. We hypothesize that MDW is broadly associated with illness severity related to sepsis and serious infection in children.

The right care in the right place: a scoping review of digital health education and training for rural healthcare workers.

Background: Digital health offers unprecedented opportunities to enhance health service delivery across vast geographic regions. However, these benefits can only be realized with effective capabilities and clinical leadership of the rural healthcare workforce. Little is known about how rural healthcare workers acquire skills in digital health, how digital health education or training programs are evaluated and the barriers and enablers for high quality digital health education and training.

Lessons in Cultural Adaptations: Translation of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Cervical Cancer Module From English to Chichewa in Malawi.

Introduction: To complete a culturally appropriate translation of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Cervical Cancer module (QLQ-CX24) from English to Chichewa (one of the official languages of Malawi) in preparation for postsurgical outcomes research in rural Malawian cervical cancer patients.

Methods: Following the EORTC translation procedure manual, two distinct forward translations from English were reconciled into a preliminary Chichewa translation, followed by two distinct back-translations to English. The English back-translation was reconciled and the translation report sent for discussion and proofreading by EORTC; this was followed by pilot testing.

Psychometric Testing of a Scale Measuring Preceptor Preparedness: The Cap-ExPresS Study.

Preceptors educate nursing students to practice as novice, generalist nurses. There are no instruments measuring preceptor preparedness. The purpose of this study was to psychometrically test the Capstone-Experience Preceptor Preparedness Scale (Cap-ExPresS™).

Impact of a 7-day homogeneous diet on interpersonal variation in human gut microbiomes and metabolomes.

Gut microbiota metabolism of dietary compounds generates a vast array of microbiome-dependent metabolites (MDMs), which are highly variable between individuals. The uremic MDMs (uMDMs) phenylacetylglutamine (PAG), p-cresol sulfate (PCS), and indoxyl sulfate (IS) accumulate during renal failure and are associated with poor outcomes. Targeted dietary interventions may reduce toxic MDM generation; however, it is unclear if inter-individual differences in diet or gut microbiome dominantly contribute to MDM variance.

PTH 1-34 Replacement Therapy Has Minimal Effect on Quality of Life in Patients With Hypoparathyroidism.

In addition to hypocalcemia, patients with hypoparathyroidism report poor quality of life (QOL), complaining of fatigue and "brain fog." Parathyroid hormone (PTH) therapy can effectively manage hypocalcemia; however, the effects of PTH treatment on QOL are unclear. Thirty-one patients with hypoparathyroidism were treated in an open-label study with full replacement subcutaneous PTH 1-34 twice daily for up to 5.

A metabolomics pipeline for the mechanistic interrogation of the gut microbiome.

Gut microorganisms modulate host phenotypes and are associated with numerous health effects in humans, ranging from host responses to cancer immunotherapy to metabolic disease and obesity. However, difficulty in accurate and high-throughput functional analysis of human gut microorganisms has hindered efforts to define mechanistic connections between individual microbial strains and host phenotypes. One key way in which the gut microbiome influences host physiology is through the production of small molecules, yet progress in elucidating this chemical interplay has been hindered by limited tools calibrated to detect the products of anaerobic biochemistry in the gut.

Neutrophil dysfunction in cystic fibrosis.

Background: Excessive neutrophil inflammation is the hallmark of cystic fibrosis (CF) airway disease. Novel technologies for characterizing neutrophil dysfunction may provide insight into the nature of these abnormalities, revealing a greater mechanistic understanding and new avenues for CF therapies that target these mechanisms.

Methods: Blood was collected from individuals with CF in the outpatient clinic, CF individuals hospitalized for a pulmonary exacerbation, and non-CF controls.

Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice.

Loss-of-function mutations in the copper (Cu) transporter ATP7A cause Menkes disease. Menkes is an infantile, fatal, hereditary copper-deficiency disorder that is characterized by progressive neurological injury culminating in death, typically by 3 years of age. Severe copper deficiency leads to multiple pathologies, including impaired energy generation caused by cytochrome c oxidase dysfunction in the mitochondria.

PET Imaging of Phosphodiesterase-4 Identifies Affected Dysplastic Bone in McCune-Albright Syndrome, a Genetic Mosaic Disorder.

McCune-Albright syndrome (MAS) is a mosaic disorder arising from gain-of-function mutations in the gene, which encodes the 3',5'-cyclic adenosine monophosphate (cAMP) pathway-associated G-protein, Gα. Clinical manifestations of MAS in a given individual, including fibrous dysplasia, are determined by the timing and location of the mutation during embryogenesis, the tissues involved, and the role of Gα in the affected tissues. The Gα mutation results in dysregulation of the cAMP signaling cascade, leading to upregulation of phosphodiesterase type 4 (PDE4), which catalyzes the hydrolysis of cAMP.

The human gut chemical landscape predicts microbe-mediated biotransformation of foods and drugs.

Microbes are nature's chemists, capable of producing and metabolizing a diverse array of compounds. In the human gut, microbial biochemistry can be beneficial, for example vitamin production and complex carbohydrate breakdown; or detrimental, such as the reactivation of an inactive drug metabolite leading to patient toxicity. Identifying clinically relevant microbiome metabolism requires linking microbial biochemistry and ecology with patient outcomes.

Bringing microbiome-drug interaction research into the clinic.

Our understanding of the scope and clinical relevance of gut microbiota metabolism of drugs is limited to relatively few biotransformations targeting a subset of therapeutics. Translating microbiome research into the clinic requires, in part, a mechanistic and predictive understanding of microbiome-drug interactions. This review provides an overview of microbiota chemistry that shapes drug efficacy and toxicity.

Treatment of Autosomal Dominant Hypocalcemia Type 1 With the Calcilytic NPSP795 (SHP635).

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism caused by heterozygous, gain-of-function mutations of the calcium-sensing receptor gene (CAR). Individuals are hypocalcemic with inappropriately low parathyroid hormone (PTH) secretion and relative hypercalciuria. Calcilytics are negative allosteric modulators of the extracellular calcium receptor (CaR) and therefore may have therapeutic benefits in ADH1.

Gynecologic and reproductive outcomes in fibrous dysplasia/McCune-Albright syndrome.

Background: Autonomous ovarian activation with recurrent estrogen-producing cysts is a hallmark feature of the rare bone and endocrine disorder fibrous dysplasia/McCune-Albright syndrome. Precocious puberty in girls with McCune-Albright syndrome has been well-described, however long-term effects on gynecologic and reproductive function are unknown. Concerningly, case reports have described poor skeletal outcomes associated with pregnancy in women with fibrous dysplasia.

Structure-Guided Drug Design of 6-Substituted Adenosine Analogues as Potent Inhibitors of Mycobacterium tuberculosis Adenosine Kinase.

Mycobacterium tuberculosis adenosine kinase (MtbAdoK) is an essential enzyme of Mtb and forms part of the purine salvage pathway within mycobacteria. Evidence suggests that the purine salvage pathway might play a crucial role in Mtb survival and persistence during its latent phase of infection. In these studies, we adopted a structural approach to the discovery, structure-guided design, and synthesis of a series of adenosine analogues that displayed inhibition constants ranging from 5 to 120 nM against the enzyme.

Age-Related Changes and Effects of Bisphosphonates on Bone Turnover and Disease Progression in Fibrous Dysplasia of Bone.

Fibrous dysplasia (FD) is a mosaic disease in which bone is replaced with fibro-osseous tissue. Lesions expand during childhood, reaching final burden by age 15 years. In vitro data suggest that disease activity decreases in adulthood; however, there is no clinical data to support this concept.

Minimal Clinically Important Improvement of Routine Assessment of Patient Index Data 3 in Rheumatoid Arthritis.

Objective: To estimate minimal clinically important improvement (MCII) of RAPID-3 (Routine Assessment of Patient Index Data 3) in rheumatoid arthritis (RA).

Methods: RAPID-3 was computed before and after treatment escalation in a prospective study of adults with active RA. Patient judgment of improvement was used as the standard for a receiver-operating characteristic curve, from which MCII was estimated.

Autoimmune hyperphosphatemic tumoral calcinosis in a patient with FGF23 autoantibodies.

Hyperphosphatemic familial tumoral calcinosis (HFTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is an autosomal recessive disorder of ectopic calcification due to deficiency of or resistance to intact fibroblast growth factor 23 (iFGF23). Inactivating mutations in FGF23, N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO (KL) have been reported as causing HFTC/HHS. We present what we believe is the first identified case of autoimmune hyperphosphatemic tumoral calcinosis in an 8-year-old boy.

Clinical and Radiographic Gastrointestinal Abnormalities in McCune-Albright Syndrome.

Context: McCune-Albright syndrome (MAS) is a rare disorder characterized by fibrous dysplasia of bone, café-au-lait macules, and hyperfunctioning endocrinopathies. It arises from somatic gain-of-function mutations in GNAS, which encodes the cAMP-regulating protein Gαs. Somatic GNAS mutations have been reported in intraductal papillary mucinous neoplasms (IPMNs) and various gastrointestinal (GI) tumors.