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Background: Acute chest syndrome (ACS) is the leading cause of mortality, accounting for 25% of all deaths among individuals with sickle cell disease (SCD). There is a lack of evidence-based laboratory and clinical risk stratification guidelines for the diagnosis and management of ACS., Study Design and Methods: To better understand physician practices for the management of ACS in the United States, we created an ACS Working Group including hematology and transfusion medicine physicians from four different SCD treatment centers in the United States. The working group created a physician survey that included physician demographics and ACS diagnostic criteria that they had to rate. The survey also included three case scenarios to assess physician attitudes about the management of ACS. Management options included supportive and preventive strategies in addition to transfusion therapy options., Results: Out of 455 physicians who received the survey, 195 responded (response rate = 43%). The respondents were primarily hematology/oncology physicians. The responses showed wide variability among physicians in how diagnostic criteria for ACS are used and how physicians risk-stratify ACS patients in their practice. The responses also reflected variability in the use of transfusions for ACS., Discussion: Based on our results, we conclude that ACS is diagnosed and managed inconsistently among expert physicians, especially in their transfusion practices due to a lack of consensus on risk stratification criteria. Our data suggest an urgent need for well-designed prospective studies to provide evidence-based guidelines and minimize management variability among physicians who care for individuals with SCD and ACS., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Interval colorectal cancers (I-CRCs) arise during the interval time period between scheduled colonoscopies. Predicting which patients are at risk of I-CRCs remains an elusive undertaking, but evidence would suggest that most I-CRCs arise from lesions missed on index endoscopy. The procedural factors that lead to missed lesions are numerous and lack consensus in the literature. In Canada, the province of Newfoundland and Labrador has the highest incidence of CRCs. In this study our aim was to examine I-CRCs (3-60 months after last colonoscopy) in NL through a population-level analysis covering 67% of the province from 2001-2018. We estimated the I-CRC rate to be up to 9.3%. Median age of I-CRC diagnosis was 67.1 years with an interval time of 2.9 years. About 57% of these tumors occurred proximal to the splenic flexure, with 53% presenting as local disease. No temporal differences were observed in interval time or tumor distribution. On univariate and multivariable logistical regression, risk of right-sided I-CRC did not correlate to the index colonoscopy indication, bowel preparation quality, size of largest polyp removed, colonoscopy completion rate, or stage at presentation. Improvements in synoptic reporting utilization and national registries are needed to identity risk factors and reduce I-CRC frequency.

To this day, there are limited data about the effects and management of coronavirus disease infection in pediatric patients with sickle cell disease. We present the management and successful clinical course of an 8-year-old female with homozygous sickle cell disease (SS) and severe acute chest syndrome secondary to coronavirus disease 2019 infection, complicated by cortical vein thrombosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

G-protein coupled receptors (GPCRs) typically have an amphipathic helix ("helix 8") immediately C-terminal to the transmembrane helical bundle. To date, a number of functional roles have been associated with GPCR helix 8 segments, but structure-function analysis for this region remains limited. Here, we examine helix 8 of the apelin receptor (AR or APJ), a class A GPCR with wide physiological and pathophysiological relevance. The 71 residue C-terminal tail of the AR is primarily intrinsically disordered, with a detergent micelle-induced increase in helical character. This helicity was localized to the helix 8 region, in good agreement with the recent AR crystal structure. A series of helix 8 mutants were made to reduce helicity, remove amphipathy, or flip the hydrophobic and hydrophilic faces. Each mutant AR was tested both biophysically, in the isolated C-terminal tail, and functionally in HEK 293 T cells, for full-length AR. In all instances, micelle interactions were maintained, and steady-state AR expression was efficient. However, removal of amphipathy or helical character led to a significant decrease in cell surface localization. Flipping of helix 8 amphipathic topology restored cell surface localization to some degree, but still was significantly reduced relative to wild-type. Structural integrity, amphipathy to drive membrane association, and correct topology of helix 8 membrane association all thus appear important for cell surface localization of the AR. This behavior correlates well to GPCR C-terminal tail sequence motifs, implying that these serve to specify key topological features of helix 8 and its proximity to the transmembrane domain., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Addiction, or substance use disorder (SUD), is a devastating psychiatric disease composed of multiple elemental features. As a biobehavioral disorder, escalation of drug and/or alcohol intake is both a cause and consequence of molecular neuroadaptations in central brain reinforcement circuitry. Multiple mesolimbic areas mediate a host of negative affective and motivational symptoms that appear to be central to the addiction process. Brain stress- and reinforcement-related regions such as the central amygdala (CeA), prefrontal cortex (PFC), and nucleus accumbens (NAc) also serve as central processors of ascending nociceptive input. We hypothesize that a sensitization of brain mechanisms underlying the processing of persistent and maladaptive pain contributes to a composite negative affective state to drive the enduring, relapsing nature of addiction, particularly in the case of alcohol and opioid use disorder. At the neurochemical level, pain activates central stress-related neuropeptide signaling, including the dynorphin and corticotropin-releasing factor (CRF) systems, and by this process may facilitate negative affect and escalated drug and alcohol use over time. Importantly, the widespread prevalence of unresolved pain and associated affective dysregulation in clinical populations highlights the need for more effective analgesic medications with reduced potential for tolerance and dependence. The burgeoning epidemic of prescription opioid abuse also demands a closer investigation into the neurobiological mechanisms of how pain treatment could potentially represent a significant risk factor for addiction in vulnerable populations. Finally, the continuing convergence of sensory and affective neuroscience fields is expected to generate insight into the critical balance between pain relief and addiction liability, as well as provide more effective therapeutic strategies for chronic pain and addiction., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Even though vaginal bleeding is an unusual clinical presentation in infants and young children, thorough evaluation by the pediatric urologist requires the recognition and knowledge of less-common conditions, including malignancy. Extragonadal germ cell tumors are rare in children aged <15 years, representing approximately 1% of all cancers. Because of the close collaboration between pediatric oncologists and pediatric urologists, a multidisciplinary approach to the management and treatment of these tumors includes chemotherapy and surgical resection, aiming for fertility preservation when possible. We present a 10-month-old infant with a cervical or uterine germ cell tumor and the challenges found during her treatment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Gas exchange in animals is ultimately diffusion based, generally occurring across dedicated respiratory organs. In many aquatic amphibians, however, multiple modes of gas exchange exist, allowing for the partitioning of O2 uptake and CO2 excretion between respiratory organs with different efficiencies. For example, due to the physical properties of O2 being vastly different between air and water phases, the lung and skin play disproportionately important roles in O2 uptake. Many aquatic frogs are renowned for their cutaneous gas exchange capacity, where often the majority of CO2 is excreted across the skin. Furthermore, the roles of these gas exchange organs change with the animal's behavior. Under diving conditions, most of the frog's gas exchange needs must be met by the skin. In this article, we describe an interactive undergraduate laboratory that allows a class of students to share equipment while assessing pulmonary and cutaneous respiration in frogs provided with an air/water choice and under enforced dive conditions. Concepts explored in this laboratory exercise include animal energetics, diving reflex, pulmonary and cutaneous gas exchange processes, diffusion-based gas flux, and O2 debt.

The euryhaline, amphibious mangrove killifish Kryptolebias marmoratus is known to survive weeks out of water in moist environments. We tested the hypothesis that the skin is a site of osmo- and ionoregulation in K. marmoratus. We predicted that under terrestrial conditions, gill and skin remodeling would result in an enhanced role for skin and a diminished role for the gills in osmo- and ionoregulation. Fish were exposed to water-either freshwater (FW, 1‰) or hypersaline water (saltwater [SW], 45‰)-or air over a moist surface of FW or SW for 9 d and then recovered in water. When fish were emersed for 9 d, (22)Na and (3)H-H(2)O were exchanged across the cutaneous surface. Homeostasis of whole-body Cl(-) and water levels but not of Na(+) levels was maintained over 9 d in air. In air-exposed fish, there was a significant increase in the size of skin ionocytes (in SW), a decrease in the number of skin mucous cells (in SW), and an increase in the gill interlamellar cell mass relative to those of fish in water. Gill ionocytes were mostly embedded away from the external surface in air-exposed fish, but the number and size of ionocytes increased (in FW). Interestingly, skin ionocytes formed distinct clusters of 20-30 cells. The estimated number of ionocytes over the whole skin surface was comparable to that in the gills. Overall, the findings support the hypothesis that the skin is a site of osmo- and ionoregulation in K. marmoratus in aquatic and terrestrial environments. Reversible cellular and morphological changes to the skin and gills during air exposure probably enhanced the cutaneous contribution to ion and water balance.

Background: Staphylococcus aureus is the most common cause of skin and soft-tissue infections. Methicillin-resistant S. aureus and community-acquired methicillin-resistant S. aureus have shown an increase in prevalence among soft-tissue infections over the past several years, with overall rates approaching 50 percent at the authors' institution in 2002. The object of this study was to determine the incidence of methicillin-resistant S. aureus with respect to hand infections, the antibiotic resistance pattern of methicillin-resistant S. aureus isolates, and implications for a change in antibiotic treatment algorithms for hand infections., Methods: A retrospective chart review of 761 patients with hand infections tracked by International Classification of Diseases, 9th Revision codes for finger or hand abscesses from 2001 to 2003 was performed at Parkland Memorial Hospital, Dallas, Texas. Culture results were obtained from 436 patients and analyzed for type of organism, and sensitivity profiles were obtained for all methicillin-resistant S. aureus isolates., Results: The median age of 761 patients was 40 years (range, 16 to 77 years); 71 percent were male and 28 percent were female. Of the 436 cultures reviewed, 371 (85 percent) had organisms identified. Methicillin-resistant S. aureus was the dominant single organism in hand infections cultured in all 3 years. The overall methicillin-resistant S. aureus rate was 61 percent of all hand infections in 2003. The percentage of S. aureus isolates identified as methicillin-resistant S. aureus increased from 55 percent to 78 percent over 3 years, up from 34 percent in 2001. Fortunately, 86 percent of these methicillin-resistant S. aureus isolates demonstrated sensitivity to conventional antibiotics, but a trend of resistance is developing., Conclusions: The incidence of community-acquired methicillin-resistant S. aureus increased from 34 percent to 61 percent over a 3-year period at the authors' county institution. An increasing trend of resistance patterns among conventional antibiotics was also demonstrated. As a result of this study, the treatment algorithm at Parkland Memorial Hospital has been modified to include abscess drainage accompanied by an antibiotic regimen targeted specifically at methicillin-resistant S. aureus. These data also have implications for broader application regarding simple skin infections and current antibiotic treatment algorithms.

Vulvovaginal candidiasis (VVC) caused by the commensal organism Candida albicans remains a significant problem among women of childbearing age, with protection against and susceptibility to infection still poorly understood. While cell-mediated immunity by CD4+ Th1-type cells is protective against most forms of mucosal candidiasis, no protective role for adaptive immunity has been identified against VVC. This is postulated to be due to immunoregulation that prohibits a more profound Candida-specific CD4+ T-cell response against infection. The purpose of this study was to examine the role of dendritic cells (DCs) in the induction phase of the immune response as a means to understand the initiation of the immunoregulatory events. Immunostaining of DCs in sectioned murine lymph nodes draining the vagina revealed a profound cellular reorganization with DCs becoming concentrated in the T-cell zone throughout the course of experimental vaginal Candida infection consistent with cell-mediated immune responsiveness. However, analysis of draining lymph node DC subsets revealed a predominance of immunoregulation-associated CD11c+ B220+ plasmacytoid DCs (pDCs) under both uninfected and infected conditions. Staining of vaginal DCs showed the presence of both DEC-205+ and pDCs, with extension of dendrites into the vaginal lumen of infected mice in close contact with Candida. Flow cytometric analysis of draining lymph node DC costimulatory molecules and activation markers from infected mice indicated a lack of upregulation of major histocompatibility complex class II, CD80, CD86, and CD40 during infection, consistent with a tolerizing condition. Together, the results suggest that DCs are involved in the immunoregulatory events manifested during a vaginal Candida infection and potentially through the action of pDCs.

This study evaluated the relationship between blood iron parameters and hepatic iron concentrations, and correlation of histologic findings with hepatic iron concentrations in a captive population of Egyptian fruit bats (Rousettus aegyptiacus) and island flying foxes (Pteropus hypomelanus). Blood samples were collected for complete blood counts, plasma biochemical profiles, serum iron concentrations, total iron-binding capacity, whole-blood lead concentrations, and plasma ferritin assays. Liver samples obtained by laparotomy were divided, with one half processed for histologic examination and the other half frozen and submitted for tissue mineral analysis. The histologic sections were scored by two blinded observers for iron deposition, necrosis, and fibrosis. The Egyptian fruit bats had significantly higher liver iron (mean = 3,669 +/- 1,823 ppm) and lead (mean = 8.9 +/- 5.8 ppm) concentrations than the island flying foxes (mean [Fe] = 174 +/- 173 ppm, mean [Pb] = 1.9 +/- 0.5 ppm). Hepatic iron concentrations significantly correlated with tissue lead concentrations, histologic grading for iron and necrosis, serum iron, transferrin saturation, and plasma ferritin (P < 0.001). Blood lead concentrations negatively correlated with tissue lead concentrations (P < 0.001). When the product of transferrin saturation and serum iron was greater than 51, an individual animal had a high probability of having iron overload. When the product of these two variables was greater than 90, there was a high probability that the animal had hemochromatosis. On the basis of this study, it appears that evaluation of serum iron, transferrin saturation, and plasma ferritin are useful and noninvasive methods for diagnosis of hemochromatosis in Egyptian fruit bats.

Several studies have found incomplete calculus removal during periodontal treatment with traditional hand curets, sonic, and ultrasonic instruments. This study evaluated the speed and effectiveness of subgingival calculus removal with new diamond-coated ultrasonic tips on single-rooted teeth. Single session subgingival scaling and root planing was performed on 80 teeth with 5 to 12 mm probing depths in 15 patients. Each patient provided groups of 4 teeth that were randomly treated with either hand curets (HAND); standard smooth ultrasonic tip (US); or fine grit (FINDIAM) or medium grit (MEDDIAM) diamond-coated ultrasonic tips. The time taken to reach the therapeutic endpoint of a clean, smooth root surface in a defined region on each tooth with each instrument by the 3 therapists with differing experience levels was recorded. The teeth were then atraumatically extracted, stored in a surfactant, photographed at 10X, and the percent of calculus present in the area of the pocket or on a comparable control surface calculated by histometric point counting. ANOVA and paired t tests showed that mean percent remaining calculus on treated versus control surfaces was HAND 4.6 +/- 5.3 versus 57.5 +/- 28.2, US 4.7 +/- 6.4 versus 54.4 +/- 25.9, FINDIAM 4.3 +/- 5.2 versus 37.5 +/- 22.1, and MEDDIAM 3.4 +/- 4.2 versus 50.7 +/- 20.1, respectively (all P < 0.01). The mean time in seconds to reach the clinical endpoint ranged from HAND 289 +/- 193, US 194 +/- 67, FINDIAM 167 +/- 71, to MEDDIAM 147 +/- 92. All powered instruments were significantly faster than HAND (P < 0.05), but did not differ from each other. On a 0 = "smooth" to 3 = "rough" scale, most often HAND resulted in "smooth" surfaces (10/20), the powered tips of all types "slight" surface roughness (10/20 each), and US the most "moderate" roughness (7/20). There were no differences in percent calculus remaining, surface roughness, or time spent among the 3 treating clinicians despite their varying experience levels. The results of this study showed that percent calculus remaining was <5% with all the instruments given time ad libitum on a given root surface. Root roughness was generally slightly greater with all 3 powered tips. All of the powered instruments took significantly less time than the HAND. Both DIAM tips took less time than US. Diamond-coated ultrasonic tips appeared to be much more efficient than HAND or US in removing calculus in moderate-deep probing depths on single-rooted teeth in vivo.

Adequate root preparation in periodontal procedures includes the removal of plaque, calculus, and perhaps contaminated cementum and dentin. The purpose of this study was to evaluate and compare the amount of root surface removal and residual surface texture using similarly shaped regular (US) and both fine (FINDIAM) and medium (MEDDIAM) grit diamond-coated ultrasonic inserts. Forty-five (45) premolars extracted for orthodontic reasons were randomly divided into 3 groups of 15 teeth each. They were individually mounted in a jig and instrumented with a standardized 500 gram force while they were moved a precise horizontal distance of 12 mm over a 1.2 second period using specially designed and computer controlled instrumentation. Three measurements were made to the nearest 0.0005" at 3 points along the test area before instrumentation and after 10 and 20 strokes. The mean depth of root structure removed was US 5.8 +/- 6.6 microns, FINDIAM 50.1 +/- 14.2 microns, MEDDIAM 30.8 +/- 12.1 microns, after 10 strokes, and US 12.7 +/- 10.9 microns, FINDIAM 83.3 +/- 20.1 microns, MEDDIAM 58.7 +/- 17.9 microns after 20 strokes, respectively. All 3 instruments were different from each other (P < 0.001) in the 10 stroke group, while in the 20 stroke group FINDIAM and MEDDIAM were different from US (P < 0.001), but not from each other. Only FINDIAM showed a significant difference between 10 and 20 stroke values for depth of root removal. Modified loss of tooth substance index SEM scores indicated increasingly greater root surface roughness from US to FINDIAM to MEDDIAM. Substantially greater root surface removal and greater residual root surface roughness occurred with diamond-coated ultrasonic inserts under standardized in vitro conditions. These results suggest that caution should be used with diamond-coated ultrasonic instruments during periodontal root planing procedures.

Light microscopic examination of the mast cell distribution in various oral tissues in germ-free and conventional beagle dogs revealed no differences between the two animals. Mast cells were observed in all tissues examined, with an increasing order of incidence as follows: cervical lymph node, parotid and submandibular glands, marginal gingivae, buccal mucosa and the middle one-third of the tongue. All four types (round, oval, elongated, and pseudopodial) of mast cells cell shapes previously described in the literature were observed. The marginal gingivae associated with the mandibular, second bicuspids was examined by light microscopy and was classified as to degree of inflammatory involvement. In a comparison of germ-free and conventional animals, the distribution of the degree of inflammation proved to be random. Correlation between mast cell densities and the degree of inflammatory infiltration was not statistically significant. However, mast cells tended to decrease as the inflammation became more severe. Electron microscopic examination of mast cells in the buccal mucosa revealed no difference in morphology of cells from germ-free or conventional animals. Cytoplasmic granules were of two basic types, one exhibited an amorphous matrix of uniform density and the other consisted of laminated coils of various sizes and densities.