Placenta and Intestinal Injury in Preterm Infants.

Necrotizing enterocolitis (NEC) is one of the most common gastrointestinal conditions affecting 6 to 10% of low-birth-weight infants and remains a leading cause of death. The risk factors associated with NEC are complex and multifactorial, including preterm birth and intrauterine exposure to inflammation and hypoxia. Chorioamnionitis has been associated with intestinal injury in animal and human clinical studies. This review presents current evidence about the clinical impact of the intrauterine environment on intestinal injury during pregnancy and postpregnancy. We present information from our own clinical and laboratory research in conjunction with information collected from an extensive search in the databases PubMed, EMBASE, and Scopus. Prospective multicenter studies, including accurate and precise clinical, maternal, and laboratory predictors (e.g., inflammatory biomarkers), will help identify the mechanisms associated with the placental pathology, the development of NEC, and the impact of in utero-triggered inflammation on the clinical outcomes. Filling the knowledge gap to link the inflammatory surge to postnatal life will aid in identifying at-risk infants for NEC in a timely manner and facilitate the development of novel immunomodulatory treatments or interventions to improve the outcomes of these vulnerable infants. KEY POINTS: · Placental inflammatory and vascular lesions are associated with NEC severity.. · Higher grade chorioamnionitis with a fetal response is associated with an increased risk of surgical NEC.. · There is a need for routine bedside utilization of placenta pathology in clinical decision-making..

Efficient small fragment sequencing of human, cow, and bison miRNA, small RNA or csRNA-seq libraries using AVITI.

Next-Generation Sequencing (NGS) catalyzed breakthroughs across various scientific domains. Illumina's sequencing by synthesis method has long been essential for NGS but emerging technologies like Element Biosciences' sequencing by avidity (AVITI) represent a novel approach. It has been reported that AVITI offers improved signal-to-noise ratios and cost reductions. However, the method relies on rolling circle amplification which can be impacted by polymer size, raising questions about its efficacy sequencing small RNAs (sRNA) molecules including microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), and others that are crucial regulators of gene expression and involved in various biological processes. In addition, capturing capped small RNAs (csRNA-seq) has emerged as a powerful method to map active or "nascent" RNA polymerase II transcription initiation in tissues and clinical samples. Here, we report a new protocol for seamlessly sequencing short DNA fragments on the AVITI and demonstrate that AVITI and Illumina sequencing technologies equivalently capture human, cattle (Bos taurus) and the bison (Bison bison) sRNA or csRNA sequencing libraries, augmenting the confidence in both approaches. Additionally, analysis of generated nascent transcription start sites (TSSs) data for cattle and bison revealed inaccuracies in their current genome annotations and highlighted the possibility and need to translate small RNA sequencing methodologies to livestock. Our accelerated and optimized protocol therefore bridges the advantages of AVITI sequencing and critical methods that rely on sequencing short DNA fragments.

Clinical Correlates of Cholestasis in Preterm Infants with Surgical Necrotizing Enterocolitis.

Background: We sought to investigate the clinical determinants and outcomes of cholestasis in preterm infants with surgical necrotizing enterocolitis (sNEC). Methods: Retrospective comparison of clinical information in preterm infants who developed cholestasis vs those who did not. Results: Sixty-two (62/91, 68.1%) infants with NEC developed cholestasis at any time following the onset of illness. Cholestasis was seen more frequently in those who had received ionotropic support at 24 hours following sNEC diagnosis (87.1% vs 58.6%; p = 0.002), had higher mean C-reactive protein levels 2 weeks after NEC diagnosis (p = 0.009), had blood culture-positive sepsis [25 (40.3%) vs 4 (13.8%); p = 0.011], received parenteral nutrition (PN) for longer durations (108.4 ± 56.63 days vs 97.56 ± 56.05 days; p = 0.007), had higher weight-for-length z scores at 36 weeks' postmenstrual age [-1.0 (-1.73, -0.12) vs -1.32 (-1.76, -0.76); p = 0.025], had a longer length of hospital stay (153.7 ± 77.57 days vs 112.51 ± 85.22 days; p = 0.024), had intestinal failure more often (61% vs 25.0%, p = 0.003), had more surgical complications (50% vs 27.6%; p = 0.044), and had >1 complication (21% vs 3.4%; p = 0.031). Using linear regression, the number of days after surgery when feeds could be started [OR 15.4; confidence interval (CI) 3.71, 27.13; p = 0.009] and the postoperative ileus duration (OR 11.9, CI 1.1, 22.8; p = 0.03) were independently associated with direct bilirubin between 2 and 5 mg/dL (mild-moderate cholestasis) at 2 months of age. The duration of PN was independently associated with direct bilirubin >5 mg/dL (severe cholestasis) at 2 months of age in these patients. Conclusion: Cholestasis was seen in 68% of infants following surgical NEC. The most likely contributive factors are intestinal failure and subsequent PN dependence for longer periods. Our data suggest that identification and prevention of risk factors such as sepsis and surgical complications and early feeds following NEC surgery may improve outcomes.

Feeding during hibernation shifts gene expression toward active season levels in brown bears (Ursus arctos).

Hibernation in bears involves a suite of metabolical and physiological changes, including the onset of insulin resistance, that are driven in part by sweeping changes in gene expression in multiple tissues. Feeding bears glucose during hibernation partially restores active season physiological phenotypes, including partial resensitization to insulin, but the molecular mechanisms underlying this transition remain poorly understood. Here, we analyze tissue-level gene expression in adipose, liver, and muscle to identify genes that respond to midhibernation glucose feeding and thus potentially drive postfeeding metabolical and physiological shifts. We show that midhibernation feeding stimulates differential expression in all analyzed tissues of hibernating bears and that a subset of these genes responds specifically by shifting expression toward levels typical of the active season. Inferences of upstream regulatory molecules potentially driving these postfeeding responses implicate peroxisome proliferator-activated receptor gamma (PPARG) and other known regulators of insulin sensitivity, providing new insight into high-level regulatory mechanisms involved in shifting metabolic phenotypes between hibernation and active states.

An Update on Pediatric Acute Hematogenous Osteomyelitis in New Zealand - A Decade on.

INTRODUCTION: New Zealand (NZ) has high rates of pediatric acute hematogenous osteomyelitis (AHO) with males and children of Pasifika and Maori ethnicity overrepresented. AIMS: To update the incidence of Pediatric AHO over 10 years, identifying trends in presentation, organisms, treatment, and outcomes. METHODS: A 10-year retrospective review of children aged 6 weeks to 15 years admitted with Pediatric AHO across two centers from 2008 to 2017. Demographic data, features of presentation, investigations, management, and complications were collected. Incidence was calculated from census data. Data were compared with our osteomyelitis database from the previous decade. (1). RESULTS: 796 cases were identified. The incidence was 18 per 100,000 per annum. The average age was 7.7 years. Pasifika and Maori children are overrepresented (57%). 370 children (51%) came from low socioeconomic areas. Methicillin-sensitive Staphylococcus aureus was the most common pathogen (87%). Methicillin-resistant Staphylococcus aureus (MRSA) rates are low (4.4%). Forty-four (5.5%) children were admitted to the Pediatric Intensive Care Unit (PICU) with 9% mortality. The mean duration of antibiotics was 40 days. 325 children (41%) had surgery. Chronic infection has increased from 1.7% to 5.7%. CONCLUSIONS: NZ has high rates of AHO, however, the incidence has decreased from the previous decade. Males, those in low socioeconomic areas, Pasifika and Maori have high disease burden. The use of MRI as a diagnostic modality has increased. Future studies should focus on improving treatment via prospective analysis and reporting long-term morbidity to improve outcomes for children with severe disease and reduce rates of chronic infection.

Mobile data security: instant messaging in orthopaedics.

BACKGROUND: Instant messaging via WhatsApp is used within hospital teams. Group messaging can lead to efficient and non-hierarchical communication. Despite being end-to-end encrypted, WhatsApp is owned by Facebook, raising concerns regarding data security. The aims of this study were: (1) to record the prevalence of WhatsApp group instant messaging amongst clinical teams; (2) to ascertain clinician attitudes towards use of instant messaging and (3) to gauge clinicians' awareness of best practice regarding mobile data protection. METHODS: Over a two-week period in May 2018, clinical nurse specialists in the Auckland District Health Board Orthopaedic department retrospectively collected data from all five team WhatsApp group message threads recording quantity of messages sent and the nature of the messages. Concurrently individuals in these WhatsApp groups completed an anonymous survey of their use of WhatsApp and their awareness of local data security policies and practice. RESULTS: One thousand three hundred and sixty messages were sent via WhatsApp in a two-week period. 384 (28%) of the messages contained patient identifiable data. Thirty-six photos were shared. Participants rated use of WhatsApp at 9.1/10 - extremely beneficial. Sixty-five percent of clinicians reported they had not read or were unaware of the ADHB policies regarding mobile devices and information privacy and security. CONCLUSION: WhatsApp use is widespread within the Orthopaedic department and is the preferred platform of communication with many perceived benefits. Data security is a risk and implementation of appropriate guidelines to assist clinicians in achieving best practice is crucial to ensure patient data remains protected.

Differential Expression of CB1 Cannabinoid Receptor and Cannabinoid Receptor Interacting Protein 1a in Labor.

Background: The endocannabinoid system is present in multiple organ systems and is involved in smooth muscle regulation, immune function, neuroendocrine modulation, and metabolism of tissues. Limited data are available regarding the presence and role of this system in reproductive tissues. Components of the endocannabinoid system have been identified in myometrial and placental tissues. However, no study has investigated differential expression of the endocannabinoid system in labor. Objectives: The purpose of this study was to identify and quantify two components of the endocannabinoid system, the CB1 cannabinoid receptor and cannabinoid receptor interacting protein 1a (CRIP1a) in uterine and placental tissues, and to determine if there is differential expression in tissues exposed to labor. We hypothesized that CB1 cannabinoid receptor concentration would be altered in uterine and placental tissue exposed to labor compared with tissues not exposed to labor. Study Design: Uterine and placental tissue samples were collected in nine laboring and 11 nonlaboring women undergoing cesarean delivery. CB1 cannabinoid receptor and CRIP1a presence and quantification were evaluated using western blot, immunohistochemistry, and real-time quantitative polymerase chain reaction. Statistical comparisons of laboring and nonlaboring subjects were made for uterine and placental tissue using a Mann-Whitney test. Results: Immunohistochemistry demonstrated positive staining for CB1 cannabinoid receptors and CRIP1a in uterine tissue. The protein abundance of CB1 cannabinoid receptor in uterine tissue was significantly lower in tissues exposed to labor (p=0.01). The protein abundance of CRIP1a was lower in uterine tissue exposed to labor but did not reach statistical significance (p=0.06). mRNA expression of CB1 cannabinoid receptor (p=0.20) and CRIP1a (p=0.63) did not differ in labored compared with nonlabored uterine tissues. Conclusions: Our findings of diminished protein density of CB1 cannabinoid receptor in uterine tissue exposed to labor support the hypothesis that the endocannabinoid system plays a role in parturition. Our data add to the growing body of evidence indicating the endocannabinoid system is of importance for successful reproduction and support the need for additional research investigating this complex system as it pertains to labor. ClinicalTrials.gov ID: NCT03752021.

Fatal systemic (paradoxical) air embolism diagnosed by postmortem funduscopy.

Air embolism is often unrecognized and underreported. Published case reports or case series describe only rare fundal examinations of retinal air emboli (RAE)-a distinctive sign of systemic air embolism. We report an infant, found unresponsive at home, who died in the emergency department after unsuccessful resuscitative efforts. Before the autopsy, diagnostic RAE were recognized and imaged during postmortem funduscopy. Postmortem radiography and an autopsy confirmed systemic (paradoxical) air embolism due to inflicted abdominal and thoracic blunt force injuries. While a few descriptions and illustrations of RAE occur in case reports, we found no published photographic images of RAE in infants, children, or adults. This case report describes and photographically documents classic RAE associated with fatal systemic (paradoxical) air embolism. Complementing postmortem radiography and judicious autopsy techniques, the detection of RAE can aid pathologists in diagnosing systemic air embolism.

Molecular and clinicopathologic characterization of intravenous leiomyomatosis.

Intravenous leiomyomatosis (IVL) is an unusual uterine smooth muscle proliferation that can be associated with aggressive clinical behavior despite a histologically benign appearance. It has some overlapping molecular characteristics with both uterine leiomyoma and leiomyosarcoma based on limited genetic data. In this study, we assessed the clinical and morphological characteristics of 28 IVL and their correlation with molecular features and protein expression, using array comparative genomic hybridization (aCGH) and Cyclin D1, p16, phosphorylated-Rb, SMARCB1, SOX10, CAIX, SDHB and FH immunohistochemistry. The most common morphologies were cellular (n = 15), usual (n = 11), and vascular (n = 5; including 3 cellular IVL showing both vascular and cellular features). Among the immunohistochemical findings, the most striking was that all IVL showed differential expression of either p16 or Cyclin D1 in comparison to surrounding nonneoplastic tissue. Cytoplasmic phosphorylated-Rb was present in all but one IVL with hyalinization. SMARCB1, FH, and SDHB were retained; S0X10 and CAIX were not expressed. The most common genetic alterations involved 1p (39%), 22q (36%), 2q (29%), 1q (25%), 13q (21%), and 14q (21%). Hierarchical clustering analysis of recurrent aberrations revealed three molecular groups: Groups 1 (29%) and 2 (18%) with associated del(22q), and Group 3 (18%) with del(10q). The remaining IVL had nonspecific or no alterations by aCGH. Genomic index scores were calculated for all cases and showed no significant difference between the 14 IVL associated with aggressive clinical behavior (extrauterine extension or recurrence) and those without (median scores 5.15 vs 3.5). Among the 5 IVL associated with recurrence, 4 had a vascular morphology and 3 had alterations of 8q. Recurrent chromosome alterations detected herein overlap with those observed in the spectrum of uterine smooth muscle tumors and involve genes implicated in mesenchymal tumors at different sites with distinct morphological features.

Self-reported eating disorder risk in lean and non-lean NCAA Collegiate Athletes.

PURPOSE: The purpose of this present study was to examine gender differences in overall scores on the Eating Attitudes Test (EAT-26) in National Collegiate Athletic Association (NCAA) college athletes in "lean" sports versus "non-lean" sports. METHODS: Using a self-report survey design, this study examined eating disorder risk in 121 NCAA college athletes, using the EAT-26. We expected that female athletes and athletes in "lean" sports would report higher scores on the EAT-26. RESULTS: There was a significant effect of sport type (lean vs. non-lean) on eating attitudes and behaviors, with those in non-lean sports reporting higher scores, on average, on the attitudinal measure and those in lean sports reporting, on average, higher scores on the behavioral measure. There was an interaction between gender and sport type (lean vs. non-lean) on eating attitudes and behaviors. Male athletes in non-lean sports had the highest overall average scores on the attitudinal portion of the EAT-26, and males in lean sports had the lowest scores. However, on the EAT-26 behavioral portion, men in lean sports reported significantly higher scores than did men in non-lean sports. Female athletes, regardless of sport type, reported similar scores on both the EAT- 26 attitudinal and behavioral sections. CONCLUSIONS: Our findings suggest that athletes, regardless of sport type and gender, may be affected by eating disorder symptomatology. Gender differences may be smaller in athletic populations than previously thought. Sport type may affect whether disordered eating symptomatology presents as attitudinal or behavioral in nature, especially in male athletes. LEVEL OF EVIDENCE: Descriptive study, Level V.

Effect of excessive gestational weight gain on trial of labour after caesarean: A retrospective cohort study.

BACKGROUND: Counselling women for and managing birth after caesarean section are important. Research is needed on evaluation of antenatal factors that predict likelihood of successful trial of labour after caesarean section (TOLAC). AIM: To evaluate the effect of gestational weight gain on mode of delivery in women having TOLAC. MATERIALS AND METHODS: A retrospective cohort study of eligible women who underwent TOLAC (January 2012 to July 2015) at a large urban hospital. Gestational weight gain was classified as 'excessive' or 'not excessive' based on calculated pre-pregnancy body mass index. Multivariable logistic regression analysis was performed to estimate the association of gestational weight gain and vaginal birth, adjusting for socio-demographic and pregnancy-related factors. RESULTS: Of 534 women, those who gained excessive weight were less likely to have a vaginal birth as women who did not (adjusted odds ratio (aOR) 0.48, 95% confidence interval (CI) 0.29-0.81)). Women with previous vaginal birth were more likely to have a vaginal birth (aOR 3.74, 95% CI 1.90-7.36), while women ≥35, women who had an epidural, and women who delivered at 40 weeks, were less likely (aOR 0.58, 95% CI 0.35-0.97, aOR 0.12, 95% CI 0.07-0.22, and aOR 0.53, 95% CI 0.31-0.91, respectively). CONCLUSIONS: Gaining excessive weight in pregnancy is potentially modifiable, and can be incorporated into individual antenatal counselling, and into risk prediction models, to assist with informed decision making around planned mode of delivery in women with previous caesarean section. Future research could focus on interventions to reduce gestational weight gain in women planning TOLAC.

Family medicine training and practice in Malawi: History, progress, and the anticipated role of the family physician in the Malawian health system.

This article analyses the development and implementation of family medicine training and practice in Malawi, with special attention given to its current status and the projected role the trained family physician will be expected to play in the future. The general aim of the paper is to briefly review the role of family physicians in rural areas, as well as to discuss the history of family medicine training in Malawi. The idea of formal family medicine training and practice in Malawi started as early as 2001 but did not come to fruition until 2011, with the start of the undergraduate clerkship in the fourth year of medical school at the University Of Malawi College Of Medicine. This energy was followed by the launch of a postgraduate training programme in early 2015. The challenges encountered in this endeavour are also reviewed. The paper concludes by discussing the expected role a Malawian family physician will play in the local context, considering the key roles that family physicians play elsewhere in Africa.

Absence of rickets in infants with fatal abusive head trauma and classic metaphyseal lesions.

PURPOSE: To determine if rickets is present in cases of infant homicide with classic metaphyseal lesions (CMLs) and other skeletal injuries. MATERIALS AND METHODS: This study was exempt from the institutional human subjects board review because all infants were deceased. An archival review (1984-2012) was performed of the radiologic and histopathologic findings of 46 consecutive infant fatalities referred from the state medical examiner's office for the evaluation of possible child abuse. Thirty infants with distal femoral histologic material were identified. Additional inclusion criteria were as follows: (a) The medical examiner determined that the infant had sustained a head injury and that the manner of death was a homicide, (b) at least one CML was evident at skeletal survey, (c) CMLs were confirmed at autopsy, and (d) non-CML fractures were also present. Nine infants (mean age, 3.9 months; age range, 1-9 months) were identified. Two pediatric radiologists independently reviewed the skeletal surveys for rachitic changes at the wrists and knees. A bone and soft tissue pathologist reviewed the distal femoral histologic slices for rickets. RESULTS: There were no radiographic or pathologic features of rickets in the cohort. CONCLUSION: The findings provide no support for the view that the CML is due to rickets. Rather, they strengthen a robust literature that states that the CML is a traumatic injury commonly encountered in physically abused infants.

High-resolution CT with histopathological correlates of the classic metaphyseal lesion of infant abuse.

BACKGROUND: The classic metaphyseal lesion (CML) is a common high specificity indicator of infant abuse and its imaging features have been correlated histopathologically in infant fatalities. OBJECTIVE: High-resolution CT imaging and histologic correlates were employed to (1) characterize the normal infant anatomy surrounding the chondro-osseous junction, and (2) confirm the 3-D model of the CML previously inferred from planar radiography and histopathology. MATERIALS AND METHODS: Long bone specimens from 5 fatally abused infants, whose skeletal survey showed definite or suspected CMLs, were studied postmortem. After skeletal survey, selected specimens were resected and imaged with high-resolution digital radiography. They were then scanned with micro-CT (isotropic resolution of 45 µm(3)) or with high-resolution flat-panel CT (isotropic resolutions of 200 µm(3)). Visualization of the bony structures was carried out using image enhancement, segmentation and isosurface extraction, together with volume rendering and multiplanar reformatting. These findings were then correlated with histopathology. RESULTS: Study of normal infant bone clarifies the 3-D morphology of the subperiosteal bone collar (SPBC) and the radiographic zone of provisional calcification (ZPC). Studies on specimens with CML confirm that this lesion is a fracture extending in a planar fashion through the metaphysis, separating a mineralized fragment. This disk-like mineralized fragment has two components: (1) a thick peripheral component encompassing the SPBC; and (2) a thin central component comprised predominantly of the radiologic ZPC. By manipulating the 3-D model, the varying appearances of the CML are displayed. CONCLUSION: High-resolution CT coupled with histopathology provides elucidation of the morphology of the CML, a strong indicator of infant abuse. This new information may prove useful in assessing the biomechanical factors that produce this strong indicator of abusive assaults in infants.

Discordant radiologic and histological dimensions of the zone of provisional calcification in fetal piglets.

BACKGROUND: Studies have shown that the fracture plane of the classic metaphyseal lesion (CML) of infant abuse occurs in the region of the primary spongiosa, encompassing a radiodense fracture fragment customarily referred to as the "zone of provisional calcification" or ZPC. However, the zone of provisional calcification is defined differently in the pathology and the imaging literature, potentially impeding efforts to understand the fundamental morphological features of the classic metaphyseal lesion. OBJECTIVE: We systematically correlated micro-CT data with histology in piglets to explore the differing definitions of the zone of provisional calcification and to elucidate the anatomical basis for divergent definitions. MATERIALS AND METHODS: The distal tibias of five normal fetal piglets were studied postmortem. The specimens were resected and imaged with digital radiography (50 µm resolution) and micro-CT (45 µm(3) isotropic resolution). Image processing techniques were applied to the micro-CT data for visualization and data analysis. The resected tissue specimens were then processed routinely and the light microscopic features were correlated with the imaging findings. RESULTS: The longitudinal dimension of the radiologic zone of provisional calcification is greater than the histological ZPC, and these dimensions are statistically distinct (P < 0.0002). The radiologic zone of provisional calcification consists of two adjoining mineralized discoid regions that span the chondro-osseous junction-a thick discoid region that encompasses the densest region of the primary spongiosa, and a thin discoid region (corresponding to the histological ZPC) that is situated in the base of the physis adjacent to the metaphysis. CONCLUSION: The correlation of the normal histology and micro-CT appearance of this dynamic and complex region provides an anatomical foundation upon which a deeper appreciation of the morphology of the classic metaphyseal lesion can be built.

Witnessed sleep-related seizure and sudden unexpected death in infancy: a case report.

Witnessed reports of sudden death are rare, but critical to deciphering its mechanism(s). We report such a death in a seemingly healthy 8-month-old boy in whom seizures and respiratory distress in the prone position were witnessed upon discovery during a sleep period. Following cardiopulmonary resuscitation, anoxic encephalopathy resulted in "brain death" and withdrawal of life support after 2 days. The autopsy did not reveal a primary anatomic cause of death. Metabolic evaluation failed to uncover an inborn error of ammonia, amino, organic, or fatty acid metabolism. Seizures in this case may have been secondary to cerebral hypoxia-ischemia complicating cardiorespiratory arrest of unknown etiology. Yet, they may represent the first manifestation of idiopathic epilepsy, triggering cardiopulmonary arrest, analogous to the terminal events postulated in sudden and unexplained death in epilepsy. This report alerts the forensic community to the possibility that sudden and unexplained death in infants may be due to seizures.

Pain management in the context of workers compensation: a case study.

The clinical management of chronic pain is a biopsychosocial challenge in itself; however, when the pain occurs in the context of workers compensation, there is even greater clinical complexity. A review of the literature shows that patients being treated for chronic pain under workers compensation are generally more distressed and have poorer outcomes both clinically and vocationally than non-compensated patients. A range of factors is identified to explain these differences, including operation of the system itself. However, a case study is presented involving a 49-year-old woman with chronic neck pain, whose clinical history illustrates how workers compensation can negatively influence outcomes, but where successful rehabilitation is also possible.