Search

Objective: The aim of this study was to evaluate the indications for maternal TORCH (Toxoplasma gondii, rubella, cytomegalovirus (CMV), and herpes simplex virus (HSV)) serology, with a focus on the yield in isolated fetal growth restriction (FGR)., Materials and Methods: A retrospective review of antenatal TORCH testing between January 2014 and December 2018 was carried out at two hospitals in Melbourne, Australia. TORCH testing ordered for pregnancy losses and stillbirth was excluded., Results: Medical records of 718 pregnancies were reviewed, representing 760 fetuses. Isolated FGR was the indication for TORCH screening in 71.2% of pregnancies. Screens ordered for isolated FGR were positive in 7.4% (95% CI 5.5-10.0%). There were 49 positive maternal immunoglobulin M (CMV = 34, Toxoplasma = 15). Two acute maternal infections during pregnancy were diagnosed (CMV = 1, Toxoplasma = 1), with both screens ordered to assess symptomatic maternal illness. There was one neonatal CMV infection, born to a woman with symptomatic primary CMV. No maternal or neonatal rubella or HSV infections were identified. We found a diagnostic yield of TORCH screening for isolated FGR of 0.0% (95% CI 0.00-0.8%). An estimated AUD$64 269.75 was expended on maternal TORCH screens in this study., Conclusion: Maternal TORCH testing for isolated FGR is of no diagnostic yield and should be abandoned., (© 2024 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Introduction: Kava, a substance derived from the Piper methysticum plant, is enjoying a surge in popularity in the United States due to its purported anxiolytic and analgesic effects. Though ichthyosiform dermopathy is a known adverse effect associated with chronic kava exposure in adults, dermopathy in a newborn due to maternal kava use has not yet been described., Case Report: This is a case of a 41-year-old woman who was taking a combination kava/kratom product throughout her pregnancy. She developed an ichthyosiform dermopathy that resolved after she stopped using the product postpartum. Her male infant had a neonatal course complicated by both neonatal opioid withdrawal syndrome, attributed to maternal kratom and buprenorphine use, as well as a diffuse ichthyosiform rash similar to descriptions of kava ichthyosiform dermopathy in adults. His neonatal course was complicated by Group B streptococcus and Serratia marscecens bacteremia (treated with antibiotics) and seizures (treated with lorazepam and phenobarbital). His rash resolved completely by day of life 22. At 9-month outpatient follow-up, he had no dermatologic abnormalities or rash recurrence., Discussion: Maternal kava use during pregnancy may cause fetal dermopathy presenting as an acquired ichthyosis. More public education is needed about the potential consequences of kava use, particularly during pregnancy., (© 2024. American College of Medical Toxicology.)

Objective: Since the global outbreak of the novel coronavirus disease 2019 (COVID-19), there have been increasing reports of children developing a croup-like cough associated with concurrent COVID-19 infection. Currently, there is not much information available regarding newborn infants and COVID-19 infection and the incidence of vertical transmission is thought to be rare. This novel case report depicts a term newborn infected at the time of birth with COVID-19 and includes details about the course of their complicated hospitalization., Study Design: A term infant, found to be infected at birth with COVID-19, developed respiratory distress resulting in transfer to our neonatal intensive care unit. Due to the increasing respiratory support requirements, endotracheal intubation was required on day of life (DOL) 7. Later, when the infant was extubated, on DOL 21, a croup-like cough developed., Results: Despite respiratory treatment with albuterol, budesonide, racemic epinephrine, lidocaine, dornase alfa, and a 10-day course of dexamethasone, the cough persisted. A prolonged hospitalization was required and eventually the infant was discharged home on 0.4 L/minute of oxygen via nasal cannula on DOL 95., Conclusion: As the COVID-19 virus mutates over time, there are some seemingly different presentations in both the pediatric and adult populations. The hypervigilance and sharing of new findings among providers are paramount in the treatment of infants with COVID-19 disease., Key Points: · Term infant with COVID-19 developed a croup-like cough.. · Usual respiratory treatment not effective with croup-like cough and COVID-19.. · COVID-19 present at birth later requiring intubation.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: The study aimed to evaluate the validity of transcutaneous bilirubin (TcB) measurements at three sites in premature infants born at 23 0/7 to 34 6/7 weeks' gestational age (GA) compared with total serum bilirubin (TSB) measurements., Study Design: A prospective study was conducted at Banner - University Medical Center Phoenix, where informed consent was obtained from the infant's parent or legally authorized representative. Cohort A was comprised of infants 23 0/7 to 28 6/7 weeks' GA and Cohort B contained subjects 29 0/7 to 34 6/7 weeks' GA. Baseline TSB measurements were collected at approximately 24 hours of life, as the standard of care and the TcB measurements were obtained from the sternum, interscapular, and buttock areas at approximately ± 30 minutes from collection of the TSB. Statistical analysis of measurements including sensitivity, specificity, positive, and negative predictive values, and the area under the receiver operator characteristic curve (AUROC) were performed., Results: A total of 166 infants were included in the study population. Cohort A consisted of 41 subjects and Cohort B contained 125 subjects. The results showed that baseline TcB measurements from the interscapular area were the most sensitive and specific with TSB levels >5.0 mg/dL in Cohort A. Baseline TcB measurements from the sternum demonstrated greatest sensitivity and specificity when the TSB level was >8.0 mg/dL in Cohort B. In general, each of the three sites in both cohorts demonstrated excellent AUROCs and negative predictive values., Conclusion: The use of a TcB meter in preterm infants can be a reliable noninvasive screening tool for hyperbilirubinemia, and it may be beneficial in decreasing painful stimuli and iatrogenic blood loss when used as an adjunct to TSB monitoring., Key Points: · Interscapular TcB is sensitive/specific in 23 to 29 weeks' GA.. · Sternal TcB is sensitive/specific in 29 to 35 weeks' GA.. · TcB readings are reliable in preterm infants.. · TcB is reliable when serum bilirubin is >5.0 mg/dL.., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: The long-term effects of prenatal coronavirus disease 2019 (COVID-19) infection on the fetal brain are mostly unknown at this time; however, there is increasing evidence being published., Case Report: Two cases of severe ventriculomegaly, neurological dysfunction, and seizures were found in neonates with prenatal exposure to COVID-19 infection during the first and third trimesters of pregnancy., Conclusion: Inflammation during the prenatal and neonatal periods may be associated with neurological disorders or injury. Despite the presumed lack of vertical transmission, post-COVID-19 syndrome and its associated inflammation may have an impact on the unborn fetus. Hyper-vigilance and dissemination of adverse findings are of significant importance as we navigate through this evolving pandemic and its effects., Key Points: · Prenatal exposure to COVID-19 may affect the fetal brain.. · There is a possibility of neonatal neurological sequelae from maternal COVID-19.. · Does maternal COVID-19 infection cause infantile seizures?., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: This study was aimed to evaluate the effect of human milk protein fortifier (HMPF) versus bovine milk protein fortifier (BMPF) on feeding tolerance defined as the time to reach full feeds and necrotizing enterocolitis (NEC) in premature very low birth weight (VLBW) infants., Study Design: A retrospective review using the BabySteps Database included 493 infants born ≤33 weeks of gestational age and ≤1,250 g (g) birth weight. A total of 218 infants fed a human milk diet (HMD) with BMPF were compared with 275 infants fed an HMD with HMPF., Results: Full feeds were reached significantly sooner in the HMPF group (median: 14 vs. 16 days, p  = 0.04). Weight at full feeds was significantly lower in the HMPF group (1,060 vs. 1110 g, p  = 0.03)., Conclusion: Using HMPF to provide an exclusively HMD allowed VLBW infants to achieve full feeds sooner, but did not affect rate of NEC compared with using a BMPF with an HMD., Key Points: · Human milk fortifiers with human milk are better than bovine human milk protein fortifiers.. · Full feeds are reached sooner with a human milk protein fortifier.. · The incidence of NEC did not change with the use of Prolacta.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To evaluate the effect of a single dose of prophylactic vancomycin prior to the removal of a peripherally inserted central catheter (PICC) in decreasing sepsis evaluations, positive cultures, and antibiotic usage in neonates., Methods: A retrospective review was conducted from December 1, 2015, through November 30, 2019, to evaluate outcomes of sepsis evaluations, positive cultures, and antibiotic usage in neonates not receiving prophylactic vancomycin prior to the discontinuation of a PICC as compared with those receiving prophylaxis vancomycin in a neonatal intensive care unit (NICU)., Results: Of the 138 neonates enrolled in the study, 82 did not receive vancomycin prophylaxis (Cohort 1), and 56 did (Cohort 2). Both cohorts were similar in sex distribution, gestational age, and PICC days. The frequency of sepsis evaluations, positive cultures, and the need for antibiotics was not found to be significant (p = 0.404, 0.703, 0.808) (Table 2). CONCLUSIONS The results did not show a statistically significant improvement in the incidence of sepsis in neonates who received prophylactic vancomycin prior to PICC discontinuation. However, there were lower percentages of sepsis evaluations, positive cultures, and antibiotics administered in the Cohort 2 patients. Although the advantage of implementing this antibiotic policy is uncertain based on this study, further research across multiple centers including a larger number of subjects may provide more conclusive results., Competing Interests: Disclosures. The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email membershipo@pediatricpharmacy.org 2022.)

Accurate prognostication of outcomes following traumatic brain injury (TBI) affects not only the aggressiveness of intervention and therapeutic decision-making but also clinicians' ability to provide reliable expectations. To investigate the relative ability of clinicians to accurately predict a patient's outcomes, compared with point-of-care prognostic models, we surveyed clinical providers of 86 patients with moderate-severe TBI at admission, Day 3, and Day 7 post-injury for a patient's predicted mortality and functional outcome at 6 months. The predicted mortality and functional outcomes were compared with actual occurrence of 14-day mortality and functional outcomes at six months. A prognostic score was then calculated utilizing the Corticoid Randomization After Significant Head Injury (CRASH) and International Mission on Prognosis and Analysis of Clinical Trials (IMPACT) models and categorized as high, intermediate, and low likelihood of mortality or poor functional outcome, and compared with clinical predictions. Overall, clinicians of varying backgrounds showed an accurate prediction of survival (87.2-97.4%) but struggled in prognosticating poor functional outcomes (24.3-36.6%). These values did not statistically improve over 7 days. Stratified CRASH (87.2%) and IMPACT (84.9%) accuracy rates were statistically better than clinical judgment alone in predicting functional outcomes ( p  < 0.0001). Prognostic models calculated at admission showed to be potentially useful, in conjunction with clinical judgment, in accurately predicting both survival and 6-month functional outcomes.

Context.—: Automated analyzers have advanced the field of clinical hematology, mandating updated complete blood count (CBC) reference intervals (RIs) to be clinically useful. Contemporary newborn CBC RI publications are mostly retrospective, which some authors have cited as one of their cardinal limitations and recommended future prospective studies., Objective.—: To prospectively establish accurate hematologic RIs for normal healthy term newborns at 24 hours of life given the limitations of the current medical literature., Design.—: This prospective study was conducted at an academic tertiary care center, and hematology samples were collected from 120 participants deemed to be normal healthy term newborns. Distributions were assessed for normality and tested for outliers. Reference intervals were values between the 2.5th percentile and 97.5th percentile., Results.—: The novel RIs obtained for this study population are as follows: absolute immature granulocyte count, 80/μL to 1700/μL; immature granulocyte percentage, 0.6% to 6.1%; reticulocyte hemoglobin equivalent, 31.7 to 38.4 pg; immature reticulocyte fraction, 35.9% to 52.8%; immature platelet count, 4.73 × 103/μL to 19.72 × 103/μL; and immature platelet fraction, 1.7% to 9.8%., Conclusions.—: This prospective study has defined hematologic RIs for this newborn population, including new advanced clinical parameters from the Sysmex XN-1000 Automated Hematology Analyzer. These RIs are proposed as the new standard and can serve as a strong foundation for continued research to further explore their value in diagnosing and managing morbidities such as sepsis, anemia, and thrombocytopenia., (© 2021 College of American Pathologists.)

Objective The aim of this study was to determine whether very low-birth-weight (VLBW) infants who had feedings withheld during all blood transfusions had a lower incidence of necrotizing enterocolitis (NEC) compared with infants who were fed during transfusions. Study Design A retrospective chart review over a 3-year period in a level-3 neonatal intensive care unit was conducted. A total of 108 inborn VLBW infants (weight range: 500-1,500 g) who had received a transfusion before 36 weeks were reviewed. Diagnosis of NEC (≥ Bell stage II), demographics, feeds, transfusions, outcomes, and variables associated with NEC were collected. Results The percentage of NEC cases was lower in infants who had feeds withheld during transfusions: 5/64 (7.8%) compared with 16/116 (13.8%) infants who were fed during transfusions. While potentially clinically important (6% absolute difference), this difference was not statistically significant (p = 0.33 by two-tailed Fisher exact test). Conclusions No significant decrease in the incidence of NEC was found when feeds were withheld during blood transfusions. Holding feeds during transfusions is not without consequences such as the need for intravenous access, additional fluids, and the disruption of optimum nutrition. Further studies are needed to establish the relationship between blood transfusions, feeds, and NEC., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: A noninvasive decision support tool for emergency transfusion would benefit triage and resuscitation. We tested whether 15 minutes of continuous pulse oximetry-derived hemoglobin measurements (SpHb) predict emergency blood transfusion better than conventional oximetry, vital signs, and invasive point-of-admission (POA) laboratory testing. We hypothesized that the trends in noninvasive SpHb features monitored for 15 minutes predict emergency transfusion better than pulse oximetry, shock index (SI = heart rate/systolic blood pressure), or routine POA laboratory measures., Methods: We enrolled direct trauma patient admissions ≥18 years with prehospital SI ≥0.62, collected vital signs (continuous SpHb and conventional pulse oximetry, heart rate, and blood pressure) for 15 minutes after admission, and recorded transfusion (packed red blood cells [pRBCs]) within 1 to 3, 1 to 6, and 1 to 12 hours of admission. One blood sample was drawn during the first 15 minutes. The laboratory Hb was compared with its corresponding SpHb reading for numerical, clinical, and prediction difference. Ten prediction models for transfusion, including combinations of prehospital vital signs, SpHb, conventional oximetry, and routine POA, were selected by stepwise logistic regression. Predictions were compared via area under the receiver operating characteristic curve by the DeLong method., Results: A total of 677 trauma patients were enrolled in the study. The prediction performance of the models, including POA laboratory values and SI (and the need for blood pressure), was better than those without POA values or SI. In predicting pRBC 1- to 3-hour transfusion, adding SpHb features (receiver operating characteristic curve [ROC] = 0.65; 95% confidence interval [CI], 0.53-0.77) does not improve ROC from the base model (ROC = 0.64; 95% CI, 0.52-0.76) with P = 0.48. Adding POA laboratory Hb features (ROC = 0.72; 95% CI, 0.60-0.84) also does not improve prediction performance (P = 0.18). Other POA laboratory testing predicted emergency blood use with ROC of 0.88 (95% CI, 0.81-0.96), significantly better than the use of SpHb (P = 0.00084) and laboratory Hb (P = 0.0068)., Conclusions: SpHb added no benefit over conventional oximetry to predict urgent pRBC transfusion for trauma patients. Both models containing POA laboratory test features performed better at predicting pRBC use than prehospital SI, the current best noninvasive vital signs transfusion predictor.

We have shown that prolonged repetitive reaching and grasping tasks lead to exposure-dependent changes in bone microarchitecture and inflammatory cytokines in young adult rats. Since aging mammals show increased tissue inflammatory cytokines, we sought here to determine if aging, combined with prolonged performance of a repetitive upper extremity task, enhances bone loss. We examined the radius, forearm flexor muscles, and serum from 16 mature (14-18 months of age) and 14 young adult (2.5-6.5 months of age) female rats after performance of a high repetition low force (HRLF) reaching and grasping task for 12 weeks. Young adult HRLF rats showed enhanced radial bone growth (e.g., increased trabecular bone volume, osteoblast numbers, bone formation rate, and mid-diaphyseal periosteal perimeter), compared to age-matched controls. Mature HRLF rats showed several indices of radial bone loss (e.g., decreased trabecular bone volume, and increased cortical bone thinning, porosity, resorptive spaces and woven bone formation), increased osteoclast numbers and inflammatory cytokines, compared to age-matched controls and young adult HRLF rats. Mature rats weighed more yet had lower maximum reflexive grip strength, than young adult rats, although each age group was able to pull at the required reach rate (4 reaches/min) and required submaximal pulling force (30 force-grams) for a food reward. Serum estrogen levels and flexor digitorum muscle size were similar in each age group. Thus, mature rats had increased bone degradative changes than in young adult rats performing the same repetitive task for 12 weeks, with increased inflammatory cytokine responses and osteoclast activity as possible causes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Key clinical features of cumulative trauma disorders include pain, muscle weakness, and tissue fibrosis, although the etiology is still under investigation. Here, we characterized the temporal pattern of altered sensorimotor behaviors and inflammatory and fibrogenic processes occurring in forearm muscles and serum of young adult, female rats performing an operant, high repetition high force (HRHF) reaching and grasping task for 6, 12, or 18 weeks. Palmar mechanical sensitivity, cold temperature avoidance and spontaneous behavioral changes increased, while grip strength declined, in 18-week HRHF rats, compared to controls. Flexor digitorum muscles had increased MCP-1 levels after training and increased TNFalpha in 6-week HRHF rats. Serum had increased IL-1beta, IL-10 and IP-10 after training. Yet both muscle and serum inflammation resolved by week 18. In contrast, IFNγ increased at week 18 in both muscle and serum. Given the anti-fibrotic role of IFNγ, and to identify a mechanism for the continued grip strength losses and behavioral sensitivities, we evaluated the fibrogenic proteins CCN2, collagen type I and TGFB1, as well as the nociceptive/fibrogenic peptide substance P. Each increased in and around flexor digitorum muscles and extracellular matrix in the mid-forearm, and in nerves of the forepaw at 18 weeks. CCN2 was also increased in serum at week 18. At a time when inflammation had subsided, increases in fibrogenic proteins correlated with sensorimotor declines. Thus, muscle and nerve fibrosis may be critical components of chronic work-related musculoskeletal disorders. CCN2 and substance P may serve as potential targets for therapeutic intervention, and CCN2 as a serum biomarker of fibrosis progression.

The therapeutic benefits of acupoint injection of vitamin K in spleen-6 (SP6) for the treatment of primary dysmenorrhea have been observed in limited clinical settings. However, menadione, the form of vitamin K most studied for treating dysmenorrhea, is not routinely used in clinical practice in North America. As part of a larger clinical trial among women aged 18-25 years with primary dysmenorrhea, we conducted a substudy to test the plasma concentration of phylloquinone (vitamin K1). We collected blood samples from four women before and 24-48 hours after an acupoint injection of phylloquinone in SP6. Despite the rapid turnover of phylloquinone observed in previous studies, we found that the plasma phylloquinone concentrations increased significantly from preinjection to 1-2 days after the injection. Interestingly, higher phylloquinone concentrations were correlated with less pain intensity among women with dysmenorrhea. Additional research is needed to understand the association between vitamin K and menstrual pain, including the role of vitamin K deficiency in inflammation and pain, and on the possible mechanisms of acupoint injection of vitamin K for the treatment of primary dysmenorrhea., (Copyright © 2014. Published by Elsevier B.V.)

Context: Dysmenorrhea, the occurrence of painful menstrual cramping of the uterus, is a major cause of activity restriction and absences from school and work among young women. Standard pharmaceuticals used to treat dysmenorrhea are not effective for all women and have side effects that limit their use. Studies elsewhere have shown beneficial effects for use of vitamin K1 as an acupoint treatment, but the acceptability of this treatment to women in the United States has been unknown., Objective: The study intended to examine the feasibility, acceptability, and preliminary effects of acupuncture point injection of vitamin K1 as an alternative treatment for primary dysmenorrhea among US women., Design: The research team conducted a pilot study using a blinded, randomized, crossover trial design., Setting: The study took place at the University of California, San Francisco (UCSF)., Participants: The study was conducted in the San Francisco Bay Area among women 18 to 25 y of age who had been diagnosed with primary dysmenorrhea. Fourteen women completed all of the study's visits., Intervention: Women with primary dysmenorrhea were randomized into 2 groups to receive bilateral injections of vitamin K1 in the Spleen-6 (SP-6) acupuncture point at the start of menstruation and then, following a 2-mo washout period, saline in a nonacupuncture point at the start of menstruation. One group received the vitamin K1 injection first, while the other group received the saline injection first., Outcome Measure: Dysmenorrhea pain intensity was measured using a 0-10 numeric rating scale (NRS), before and after injections., Results: Women had an average 2.5-point decrease in pain after a vitamin K1 injection in the SP-6 acupoint (P < .001), as compared with a 1.8-point decrease after a saline injection (P < .001). Change scores for vitamin K1, as compared with a saline injection, approached statistical significance (P < .10). Intensity and duration of menstrual symptoms, as measured by the Cox retrospective symptom scale, also decreased following injections. After participating, 94% of the women remained agreeable to receiving the injection therapy, and 77% reported they would come every month were the treatment available., Conclusions: Findings suggested high acceptability for an acupuncture point injection of vitamin K1 as treatment for primary dysmenorrhea among young women in San Francisco. Pain decreased with both treatments, with a trend toward greater pain reduction for the vitamin K1/SP-6 injection. This finding is consistent with outcomes from the Obstetrics and Gynecology Hospital in Shanghai, China, where the protocol was developed.

We examined the relationship between grip strength declines and muscle-tendon responses induced by long-term performance of a high-repetition, low-force (HRLF) reaching task in rats. We hypothesized that grip strength declines would correlate with inflammation, fibrosis and degradation in flexor digitorum muscles and tendons. Grip strength declined after training, and further in weeks 18 and 24, in reach limbs of HRLF rats. Flexor digitorum tissues of reach limbs showed low-grade increases in inflammatory cytokines: IL-1β after training and in week 18, IL-1α in week 18, TNF-α and IL-6 after training and in week 24, and IL-10 in week 24, with greater increases in tendons than muscles. Similar cytokine increases were detected in serum with HRLF: IL-1α and IL-10 in week 18, and TNF-α and IL-6 in week 24. Grip strength correlated inversely with IL-6 in muscles, tendons and serum, and TNF-α in muscles and serum. Four fibrogenic proteins, TGFB1, CTGF, PDGFab and PDGFbb, and hydroxyproline, a marker of collagen synthesis, increased in serum in HRLF weeks 18 or 24, concomitant with epitendon thickening, increased muscle and tendon TGFB1 and CTGF. A collagenolytic gelatinase, MMP2, increased by week 18 in serum, tendons and muscles of HRLF rats. Grip strength correlated inversely with TGFB1 in muscles, tendons and serum; with CTGF-immunoreactive fibroblasts in tendons; and with MMP2 in tendons and serum. Thus, motor declines correlated with low-grade systemic and musculotendinous inflammation throughout task performance, and increased fibrogenic and degradative proteins with prolonged task performance. Serum TNF-α, IL-6, TGFB1, CTGF and MMP2 may serve as serum biomarkers of work-related musculoskeletal disorders, although further studies in humans are needed.

Mitochondrial dysfunction may be central to the pathophysiology of traumatic brain injury (TBI) and often can be recognized cytologically by changes in mitochondrial ultrastructure. This study is the first to broadly characterize and quantify mitochondrial morphologic alterations in surgically resected human TBI tissues from three contiguous cortical injury zones. These zones were designated as injury center (Near), periphery (Far), and Penumbra. Tissues from 22 patients with TBI with varying degrees of damage and time intervals from TBI to surgical tissue collection within the first week post-injury were rapidly fixed in the surgical suite and processed for electron microscopy. A large number of mitochondrial structural patterns were identified and divided into four survival categories: normal, normal reactive, reactive degenerating, and end-stage degenerating profiles. A tissue sample acquired at 38 hours post-injury was selected for detailed mitochondrial quantification, because it best exhibited the wide variation in cellular and mitochondrial changes consistently noted in all the other cases. The distribution of mitochondrial morphologic phenotypes varied significantly between the three injury zones and when compared with control cortical tissue obtained from an epilepsy lobectomy. This study is unique in its comparative quantification of the mitochondrial ultrastructural alterations at progressive distances from the center of injury in surviving TBI patients and in relation to control human cortex. These quantitative observations may be useful in guiding the translation of mitochondrial-based neuroprotective interventions to clinical implementation.

Twist1 has been demonstrated to play critical roles in the early development of neural crest and mesodermally derived tissues including the limb. Twist2 has been less well characterised but its relatively late onset of expression suggests specific roles in the development of a number of organs. Expression of Twist2 within the developing limbs begins after formation of the limb bud and persists within the peripheral mesenchyme until digital rays condense. We have used RCAS-mediated overexpression in chick to investigate the function of Twist2 in limb development. Viral misexpression following injection into the lateral plate mesoderm results in a spectrum of hypoplastic limb phenotypes. These include generalized shortening of the entire limb, fusion of the autopod skeletal elements, loss of individual digits or distal truncation resulting in complete loss of the autopod. These phenotypes appear to result from a premature termination of limb outgrowth and manifest as defective growth in both the proximal-distal and anterior-posterior axes. In situ hybridisation analysis demonstrates that many components of the Shh/Grem1/Fgf regulatory loop that controls early limb growth and patterning are downregulated by Twist2 overexpression. Grem1 has a complementary expression pattern to Twist2 within the limb primordia and co-expression of both Grem1 and Twist2 results in a rescue of the Twist2 overexpression phenotype. We demonstrate that Twist proteins directly repress Grem1 expression via a regulatory element downstream of the open reading frame. These data indicate that Twist2 regulates early limb morphogenesis through a role in terminating the Shh/Grem1/Fgf autoregulatory loop., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Nature-derived antimalarials might have anticancer potential, yet no systematic reviews exist on the topic. We screened MEDLINE using an automated algorithm in a high-volume search for antimalarial agents recognized by the WHO and natural antimalarials from knowledge-resource texts and databases for reported evidence of anticancer activity. Results are reported by source (plants, fungi, marine organisms and bacteria) and anticancer mechanism. In total, 14 out of 15 nature-derived antimalarials (93%) referenced by WHO as well as 146 of 235 antimalarial natural species (62%) from our defined MEDLINE search were reported as having anticancer activity. Therefore, antimalarial natural products might provide a fertile and much needed lead in anticancer drug discovery., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We sought to determine if tendon inflammatory and histopathological responses increase in aged rats compared to young rats performing a voluntary upper extremity repetitive task, and if these changes are associated with motor declines. Ninety-six female Sprague-Dawley rats were used in the rat model of upper extremity overuse: 67 aged and 29 young adult rats. After a training period of 4 weeks, task rats performed a voluntary high repetition low force (HRLF) handle-pulling task for 2 hrs/day, 3 days/wk for up to 12 weeks. Upper extremity motor function was assessed, as were inflammatory and histomorphological changes in flexor digitorum and supraspinatus tendons. The percentage of successful reaches improved in young adult HRLF rats, but not in aged HRLF rats. Forelimb agility decreased transiently in young adult HRLF rats, but persistently in aged HRLF rats. HRLF task performance for 12 weeks lead to increased IL-1beta and IL-6 in flexor digitorum tendons of aged HRLF rats, compared to aged normal control (NC) as well as young adult HRLF rats. In contrast, TNF-alpha increased more in flexor digitorum tendons of young adult 12-week HRLF rats than in aged HRLF rats. Vascularity and collagen fibril organization were not affected by task performance in flexor digitorum tendons of either age group, although cellularity increased in both. By week 12 of HRLF task performance, vascularity and cellularity increased in the supraspinatus tendons of only aged rats. The increased cellularity was due to increased macrophages and connective tissue growth factor (CTGF)-immunoreactive fibroblasts in the peritendon. In conclusion, aged rat tendons were overall more affected by the HRLF task than young adult tendons, particularly supraspinatus tendons. Greater inflammatory changes in aged HRLF rat tendons were observed, increases associated temporally with decreased forelimb agility and lack of improvement in task success.

Background: We previously reported early tissue injury, increased serum and tissue inflammatory cytokines and decreased grip in young rats performing a moderate demand repetitive task. The tissue cytokine response was transient, the serum response and decreased grip were still evident by 8 weeks. Thus, here, we examined their levels at 12 weeks in young rats. Since aging is known to enhance serum cytokine levels, we also examined aged rats., Methods: Aged and young rats, 14 mo and 2.5 mo of age at onset, respectfully, were trained 15 min/day for 4 weeks, and then performed a high repetition, low force (HRLF) reaching and grasping task for 2 hours/day, for 12 weeks. Serum was assayed for 6 cytokines: IL-1alpha, IL-6, IFN-gamma, TNF-alpha, MIP2, IL-10. Grip strength was assayed, since we have previously shown an inverse correlation between grip strength and serum inflammatory cytokines. Results were compared to naïve (grip), and normal, food-restricted and trained-only controls., Results: Serum cytokines were higher overall in aged than young rats, with increases in IL-1alpha, IFN-gamma and IL-6 in aged Trained and 12-week HRLF rats, compared to young Trained and HRLF rats (p < 0.05 and p < 0.001, respectively, each). IL-6 was also increased in aged 12-week HRLF versus aged normal controls (p < 0.05). Serum IFN-gamma and MIP2 levels were also increased in young 6-week HRLF rats, but no cytokines were above baseline levels in young 12-week HRLF rats. Grip strength declined in both young and aged 12-week HRLF rats, compared to naïve and normal controls (p < 0.05 each), but these declines correlated only with IL-6 levels in aged rats (r = -0.39)., Conclusion: Aging enhanced a serum cytokine response in general, a response that was even greater with repetitive task performance. Grip strength was adversely affected by task performance in both age groups, but was apparently influenced by factors other than serum cytokine levels in young rats.

Background: The brain acoustic monitor (BAM), an indicator of cerebral autoregulation, has previously shown high sensitivity but low specificity for computed tomographic (CT) abnormality in patients following the clinical diagnosis of traumatic brain injury. We assessed the utility of the BAM in diagnosing mild TBI (mTBI) in patients with and without normal findings of CT scan, a population for which there are a few objective markers of disease., Methods: We prospectively studied 369 patients with mechanism of injury consistent with TBI. The diagnosis was evaluated by five methods: (a) study enrollment (i.e., mechanism of injury), (b) signs of head trauma, (c) expert physician assessment, (d) presence of initial symptoms (loss of consciousness [LOC]; amnesia), and (e) BAM. All patients had a head CT scan. We compared the BAM screen results with the diagnosis of mTBI and BAM data from 50 normal volunteers and 49 trauma control patients not thought to have TBI., Results: None of the diagnostic methods correlated well with the others. Correlation between the methods ranged from 21% to 71%. BAM discriminated between patients with mTBI versus without TBI (p<0.01) and patients with mTBI versus normal subjects (p<0.001). There were 14 patients with new abnormal findings of CT scans. A history of LOC and physical signs of head injury were associated with a new abnormality on head CT (p<0.05 and p<0.01, respectively), whereas an abnormal BAM signal was suggestive (p=0.08). The sensitivity of BAM abnormality for head CT abnormality was 100%, with a specificity of 30.14%., Conclusion: There is no gold standard for the diagnosis of mTBI. BAM screening is a useful diagnostic adjunct in patients with mTBI and may facilitate decision making. An abnormal BAM reading adds significance to LOC as a predictor of a new abnormality on head CT. In our study, opting not to CT scan patients with a normal BAM signal would have missed no new CT findings and no patients who required medical intervention for TBI, at a cost savings of $202,950., (Copyright © 2011 by Lippincott Williams & Wilkins)

Chemokines are small secreted signalling molecules best known for their roles as chemoattractants for cells of the immune system. CXCL12 and its receptor CXCR4 comprise one chemokine signalling pathway with essential functions in non-immune cell types during embryonic development. CXCL14, a chemokine-encoding gene related to CXCL12, is developmentally regulated in zebrafish and Xenopus embryos, but its role during embryogenesis remains unknown. Here we describe the embryonic expression pattern of CXCL14 in an amniote, the chick. Although expression in some regions is conserved with that of fish and frog, chick CXCL14 displays a complex pattern of expression in several novel sites. We analyse the expression pattern in the branchial arches, trigeminal placode and ganglion, inner ear, dorsal midline of the brain, somites, trunk neural tube and limb bud. Expression in several domains raises the possibility that CXCL14 may be involved in some of the same developmental events during which CXCL12-CXCR4 signalling is known to play a role.

Ethnopharmacological Relevance: Plant mixtures are understudied in ethnobotanical research., Aim of the Study: To investigate the importance of plant mixtures (remedies consisting of at least two plants) in Dominican traditional medicine., Materials and Methods: A Spanish language questionnaire was administered to 174 Dominicans living in New York City (NYC) and 145 Dominicans living in the Dominican Republic (DR), including lay persons (who self-medicate with plants) and specialists (traditional healers). Plants were identified through specimens purchased in NYC botánica shops and Latino grocery shops, and from voucher collections., Results: The percentage of mixtures as compared to single plants in plant use reports varied between 32 and 41%, depending on the geographic location (NYC or DR) and participant status (lay person or specialist). Respiratory conditions, reproductive health and genitourinary conditions were the main categories for which Dominicans use plant mixtures. Lay persons reported significantly more mixtures prepared as teas, mainly used in NYC to treat respiratory conditions. Specialists mentioned significantly more botellas (bottled herbal mixtures), used most frequently in the DR to treat reproductive health and genitourinary conditions. Cluster analysis demonstrated that different plant species are used to treat respiratory conditions as compared to reproductive health and genitourinary conditions. Interview participants believed that combining plants in mixtures increases their potency and versatility as medicines., Conclusions: The present study demonstrates the importance and complexity of plant mixtures in Dominican traditional medicine and the variation in its practices influenced by migration from the DR to NYC, shedding new light on the foundations of a particular ethnomedical system., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Objective: Higher socioeconomic status (SES) is associated with using complementary and alternative medicine (CAM) in national surveys. Less is known about how socioeconomic factors affect CAM use in US subpopulations. We examined whether the relationship between SES and CAM use differs by racial/ethnic groups., Methods: Using national survey data, we assessed education and income effects on women's CAM use in four racial/ethnic groups (Whites, Blacks, Mexican Americans, and Chinese Americans), controlling for age, health status, and geographic region. CAM use was defined as using any of 11 domains in the prior year., Results: Adjusted effects of SES on CAM use were similar among Mexican American and non-Hispanic White women--education had a distinct gradient effect, with each increasing level of education significantly more likely to use CAM; household income > or = $60,000 was associated with CAM use compared to income < $20,000. For Chinese American women, socioeconomic factors were not associated with CAM use when controlling for confounders. Although income was not associated with CAM use among African American women, college graduates were three times more likely to use CAM than those with less than a high school education, adjusting for confounders., Conclusion: SES effects on CAM use are not uniform across racial/ethnic populations. Other factors, such as culture and social networks, may interact with SES to influence CAM use in minority populations.

Background: Complementary and alternative medicine (CAM) is often used alongside conventional medical care, yet fewer than half of patients disclose CAM use to medical doctors. CAM disclosure is particularly low among racial/ethnic minorities, but reasons for differences, such as type of CAM used or quality of conventional healthcare, have not been explored., Objective: We tested the hypotheses that disclosure of CAM use to medical doctors is higher for provider-based CAM and among non-Hispanic whites, and that access to and quality of conventional medical care account for racial/ethnic differences in CAM disclosure., Methods: Bivariate and multiple variable analyses of the 2002 National Health Interview Survey and 2001 Health Care Quality Survey were performed., Results: Disclosure of CAM use to medical providers was higher for provider-based than self-care CAM. Disclosure of any CAM was associated with access to and quality of conventional care and higher among non-Latino whites relative to minorities. Having a regular doctor and quality patient-provider relationship mitigated racial/ethnic differences in CAM disclosure., Conclusion: Insufficient disclosure of CAM use to conventional providers, particularly for self-care practices and among minority populations, represents a serious challenge in medical encounter communications. Efforts to improve disclosure of CAM use should be aimed at improving consistency of care and patient-physician communication across racial/ethnic groups.

Background: Intravaginal topical microbicides are being investigated for prevention of HIV transmission. Use of vaginal microbicides will constitute a new type of practice, occurring in the context of other vaginal practices related to contraception, hygiene, and self-care, which are affected by cultural norms and personal beliefs. Given the high rate of HIV infection among black women, research on practices and decision making relevant to microbicide acceptability is needed in this population., Methods: Twenty-three black women in New York City, aged 25-64, completed in-person semistructured interviews and self-administered questionnaires. Quantitative analyses examined vaginal practices and willingness to use microbicides. Qualitative analyses explored underlying decision-making processes involved in choices regarding vaginal practices and general healthcare., Results: Willingness to use vaginal products for HIV prevention was high, especially among more educated women. Safety was a major concern, and women were cautious about using vaginal products. Whereas some viewed synthetic products as having potentially harmful side effects, others perceived natural products as risky because of insufficient testing. Choices about vaginal practices were affected by assessments of risk and efficacy, prior experience, cultural background, and general approach to healthcare., Conclusions: The majority of women in the sample expressed willingness to use a vaginal product for HIV prevention. Decision-making processes regarding vaginal practices were complex and were affected by social, cultural, and personal factors. Although specific preferences may vary, attitudes toward using a vaginal product are likely to be positive when side effects are minimal and the product is considered safe.

Background: Medical pluralism can be defined as the employment of more than one medical system or the use of both conventional and complementary and alternative medicine (CAM) for health and illness. American women use a variety of health services and practices for women's health conditions, yet no national study has specifically characterized women's medical pluralism. Our objective was to describe medical pluralism among American women., Methods: A nationally representative telephone survey of 808 women >or=18 years of age was conducted in 2001. Cross-sectional observations of the use of 11 CAM domains and the use of an additional domain--spirituality, religion, or prayer for health--during the past year are reported. Women's health conditions, treatments used, reasons for use, and disclosure to conventional physicians are described, along with predictors of CAM use., Results: Over half (53%) of respondents used CAM for health conditions, especially for those involving chronic pain. The majority of women disclosed such practices at clinical encounters with conventional providers. Biologically based CAM therapies, such as nutritional supplements and herbs, were commonly used with prescription and over-the-counter (OTC) pharmaceuticals for health conditions., Conclusions: Medical pluralism is common among women and should be accepted as a cultural norm. Although disclosure rates of CAM use to conventional providers were higher than in previous population-based studies, disclosure should be increased, especially for women who are pregnant and those with heart disease and cancer. The health risks and benefits of polypharmacy should be addressed at multiple levels of the public health system.

Objective: Earlier assessment of autism improves outcomes. In addition, children with autism have significant need for medical care. Therefore, identification of factors associated with delays in the early diagnosis of autism and with decreased access to care has the potential to lead to interventions that will improve health and well-being. The aim of this study was to determine whether differences occur in the age-specific prevalence of autism or in access to health care in children of traditionally underserved populations., Method: Data from the National Survey of Children's Health of 2003/2004 were used. Diagnosis of autism and its severity were based on parental report., Results: The prevalence of autism was lower for Latinos (26/10,000) than for non-Latinos (51/10,000). Whites and blacks had comparable rates. The lowest preschool rate of autism (16/10,000) occurred in poor children. Latinos and poor families rated their children's autism as more severe. Being black, Latino, or poor was associated with decreased access to services, while having Medicaid or State Children's Health Insurance Program was linked with better access to some services., Conclusions: Disparities in the prevalence and parent-reported severity of autism and in access to health care were found for children with autism. Programs for children in general (e.g., universal screening for autism) and programs that target traditionally underserved groups of children, their families, and their health care providers should be tested and implemented to optimize case finding of children with autism and to eliminate disparities in access to care and to early intervention.

This study provides national prevalence estimates for complementary and alternative (CAM) use, visits to doctors for health problems, and the effects of acculturation on health practices in Chinese women living in the United States. A national telephone survey of 3,172 women on their use of complementary and alternative medicine was conducted in 2001. This study focuses on a subsample of 804 Chinese-American women who were asked about health practices and service utilization. Interviews were conducted in Mandarin, Cantonese and English. Forty-one percent of Chinese-American women used some form of CAM in 2001. Socio-economic status, a common predictor of CAM use in other studies of the general population in the United States, did not predict use in this sample. Traditional Chinese medicine (TCM) is used across acculturation levels. As Chinese women adapt to American culture they tend to use a greater variety of healthcare practices and to adopt mainstream CAM practices, but they also continue to use TCM.

Objective: This study examined patterns of and reasons for use of complementary and alternative therapies among women with depression, focusing in particular on three popular types of complementary and alternative therapies-manual therapies (for example, chiropractic treatments, massage, and acupressure), herbs, and vitamins., Methods: The multiethnic sample consisted of 220 women with depression who were assessed as part of a nationally representative telephone survey of 3,068 women., Results: Fifty-four percent of these women with depression reported past-year use of complementary and alternative medicine. African-American women were less likely to use complementary and alternative therapies in general, compared with non-Hispanic white women. Other factors significantly associated with use of complementary and alternative medicine in general included being employed, being single, and having self-perceived poor health. The relationships between the sociodemographic factors and use of each of the three individually examined types of therapies differed from their relationships with use of complementary and alternative medicine in general. Participants' most commonly cited reasons for use of these therapies were wanting treatments to be based on a "natural approach," wanting treatments to be congruent with their own values and beliefs, and past experiences in which conventional medical therapies had caused unpleasant side effects or had seemed ineffective., Conclusions: It is important for mental health and other health professionals to increase their own awareness of the types of complementary and alternative therapies that their patients may be using and to improve communication with their patients about the benefits and potential risks of these therapies.

This paper explores the challenges and opportunities associated with the evaluation of treatments arising from traditional medical systems (TMS). Globalization and popular consumer-and industry-driven market forces contribute to the spread of traditional treatments, techniques and technologies, but do not necessarily ensure their usefulness or safety. The international scientific community is obliged to evaluate the safety and efficacy of these treatments because of their potential impact on global public health. Clinical evaluations of traditional treatments, however, have complex methodological and practical challenges, depending on the goals of the research and the audience for the results (country of origin; or new host countries and new patient populations). To address these challenges, the authors offer the following recommendations to identify and prioritize treatments to study and how to design study protocols. Evaluations of traditional treatments are best addressed first by collaborative, international, pragmatic studies. Protocols for observational, prospective, pragmatic pilot study (randomized and controlled, when feasible) should be designed collaboratively and executed simultaneously in the culture of origin and in new contexts. This, in turn, could determine the acceptability, usefulness and feasibility of larger randomized controlled trials (RCTs). International multicentre RCTs would have the potential benefits of evaluating safety and effectiveness and also assessing the transferability of a traditional treatment across social and cultural contexts.

Objectives: Although racial/ethnic differences in the prevalence of complementary and alternative medicine (CAM) utilization have been documented, differences in the reasons for using CAM have not been empirically assessed. In an increasingly diverse society, understanding differences in rates of and reasons for CAM use could elucidate cultural and social factors of health behaviors and inform health care improvements. The current study examines reasons for CAM use among women in four racial/ethnic groups., Design: A national telephone survey of 3172 women aged 18 years and older was conducted in four languages. Respondents were asked about their use of remedies or treatments not typically prescribed by a medical doctor. This study focuses on those women who used CAM in the previous year and their reasons for using CAM., Results: Non-Hispanic white women were most likely to cite personal beliefs for CAM use. Cost of conventional medicine was most prevalent among Mexican-American women CAM users. Physician referral, family and friends, and media sources were all equally likely to lead to CAM use in non-Hispanic white women. In contrast, informal networks of family and friends were the most important social influences of CAM use among African-, Mexican-, and Chinese-American women., Conclusions: Racial/ethnic differences in reasons for CAM use highlight cultural and social factors that are important to consider in public evaluation of the risks and benefits of CAM remedies and treatments.

Objectives: We studied the use of complementary and alternative medicine (CAM) among women in 4 racial/ethnic groups: non-Hispanic Whites, African Americans, Mexican Americans, and Chinese Americans., Methods: We obtained a nationally representative sample of women aged 18 years and older living in the United States in 2001. Oversampling obtained 800 interviews in each group, resulting in a sample of 3068 women., Results: Between one third and one half of the members of all groups reported using at least 1 CAM modality in the year preceding the survey. In bivariate analyses, overall CAM use among Whites surpassed that of other groups; however, when CAM use was adjusted for socioeconomic factors, use by Whites and Mexican Americans were equivalent. Despite the socioeconomic disadvantage of African American women, socioeconomic factors did not account for differences in CAM use between Whites and African Americans., Conclusions: CAM use among racial/ethnic groups is complex and nuanced. Patterns of CAM use domains differ among groups, and multivariate models of CAM use indicate that ethnicity plays an independent role in the use of CAM modalities, the use of CAM practitioners, and the health problems for which CAM is used.

Context: Vitamin K acupuncture point injection, a menstrual pain treatment derived from traditional Chinese medicine, has been a standard treatment in some hospitals in China since the 1980s., Objectives: To investigate the effects of vitamin K acupuncture point injection on menstrual pain in young women aged 14 to 25 from different countries and cultural backgrounds who have had unmitigated severe primary dysmenorrhea for 6 months or more., Design: Prospective, observational, clinical pilot study, Settings: One site in China (a hospital outpatient clinic in Shanghai) and 2 sites in Italy (a hospital clinic in Milan and a private gynecology practice in Verona)., Interventions: All subjects were treated with bilateral acupuncture point injection of vitamin K on the first or second day of menstrual pain. Vitamin K3 was used in China and vitamin K4 in Italy., Main Outcome Measures: Pain intensity, total duration, and average intensity of menstrual distress, hours in bed, normal daily activity restrictions, and numbers of analgesic tablets taken to relieve pain were recorded before the treatment and for 4 subsequent menstrual cycles., Results: Noticeable pain relief was observed 2 minutes after treatment, and subsequent pain reduction occurred at 30 minutes (P < .001). Subjects reported significantly fewer daily life restrictions, fewer hours in bed, less consumption of analgesic tablets, and lower scores of menstrual pain duration and intensity (P < .001). There were no adverse events. Some women experienced mild, self-limited pain at the injection site., Conclusion: Acupuncture point injection with vitamin K alleviated acute menstrual pain, and relief extended through the nontreatment follow-up cycles in this uncontrolled pilot study conducted in 2 countries. Further investigation employing controlled experimental designs is warranted.

Objective: This study describes the prevalence and patterns of use of religion and spirituality for health reasons among African-American women., Methods: Respondents were asked about their use of religion/spirituality for health reasons as part of a larger study of the prevalence and correlates of complementary and alternative medicine (CAM) use among women. In 2001, a national survey of 3,172 women, aged 18 and older, was conducted in 4 languages, with over-sampling among African-, Mexican-, and Chinese-American participants. This paper focuses on the sub-sample of 812 African-American women., Results: Overall, 43% of the African-American women reported using religion/spirituality for health reasons in the past year. Factors significantly associated with the use of religion/spirituality for health reasons included having an income of dollar 40,000-dollar 60,000, an education level of college graduate or more, or being 37-56 years of age; worse health status approached significance. African-American women utilized religion and spirituality most often for serious conditions such as cancer, heart disease, and depression. African-American women who had used religion/spirituality in the past year for health reasons were more than twice as likely to have used some form of CAM, and also more likely to have seen a medical doctor during the year prior to the interview, compared to their counterparts., Conclusion: Religion and spirituality are associated with health-seeking behaviors of African-American women. The use of religion and spirituality for health reasons warrants additional research, particularly its use for chronic and serious conditions, and its role in the health-seeking behavior of African-American women in conjunction with the utilization of conventional medicine and CAM.