Absence of Ductus Venosus: A Comparison of 2 Distinctive Fetal Autopsy Cases and Embryologic Perspectives.

In fetal circulation, oxygenated blood from the placenta flows through the umbilical vein into the ductus venosus (DV), then enters the inferior vena cava, and subsequently reaches the right atrium of the heart. The DV serves as a shunt, allowing this oxygen-rich blood to bypass the liver. The absence of the DV (ADV), also known as agenesis of the DV, is a rare congenital anomaly. Without a DV, blood from the umbilical vein must follow alternative routes to the heart. In ADV cases, blood from the umbilical vein must follow 1 of 2 primary drainage patterns: either an extrahepatic shunt or an intrahepatic shunt. This report details the antenatal ultrasound and postmortem findings of 2 fetuses diagnosed with ADV by prenatal imaging studies. The first case involved a fetus with a persistent right umbilical vein connected directly to the suprahepatic IVC, accompanied by early obliteration of the left umbilical vein and true agenesis of the DV. This fetus also had additional congenital anomalies. In contrast, the second case involved a fetus with a normal left umbilical vein that entered the liver. However, despite an ultrasound diagnosis of "absence" of the DV, a DV was present, though markedly hypoplastic and probably minimally functional or non-functional. In this case, blood from the umbilical vein likely followed an alternate intrahepatic route through the portal and hepatic veins, before reaching the heart (intrahepatic shunt). These contrasting cases emphasize the heterogeneity of vascular anomalies and embryologic origins captured by the term "ADV." Additionally, the terminology of "absence" or "agenesis" may be misleading in some purported ADV cases. Specifically, in the second case, the DV was not absent; it was markedly hypoplastic instead. This also appears to be the first reported case of a hypoplastic DV in a fetus. Both cases underscore the importance of effective collaboration and clear communication between maternal-fetal medicine specialists and pathologists.

What are the experiences of non-invasive ventilation for sleep-disordered breathing in children and young people and what outcomes matter? Perspectives of children and young people, their parents and the staff who care for them.

BACKGROUND: Non-invasive ventilation (NIV) for sleep-disordered breathing (SDB) in children and young people (CYP) can result in multiple health outcomes; however, adherence to NIV can be challenging. Suboptimally treated SDB may increase the risk of adverse consequences. Placing children's and parents' goals at the core of their SDB treatment may support adherence to NIV. To identify these health outcomes, it is necessary to gain a greater understanding of CYP's experiences of using NIV, whether they perceive any benefits from NIV use, as well as the outcomes that their parents and NIV staff identify as important. METHODS: Semi-structured qualitative interviews were conducted with nine CYP (aged 4-16 + years), 13 parents and nine healthcare professionals (HCPs); verbatim transcripts were analysed using Framework Analysis. RESULTS: CYP predominantly reported an improvement in levels of energy, focus and ability to concentrate whereas parents also identified outcomes of mood and behaviour. The majority of children showed understanding of the reasons for being prescribed NIV. A subset of children did not notice their SDB. The health outcomes identified by HCPs and parents that could result from improved overnight gas exchange are subjective measures that rely on parent and child report. Measuring these health outcomes focussed on the impact of improved sleep rather than measuring improved sleep itself. CONCLUSIONS: It is important for HCPs administering NIV to ascertain whether CYP have noticed any of their sleep-disordered breathing symptoms and any improvements from using NIV, including the relationship between benefits and side effects. Focussing on promoting understanding for CYP who are unable to link their wellbeing to their previous night's sleep may be futile and HCP strategies should concentrate on the process of tolerating the device. Parents, CYP and HCPs should collaborate to identify treatment goals specifically tailored for the child and monitor any progress against these goals.

Maternal Hemoglobin A1c in the Third-Trimester May Underestimate Maternal Hyperglycemia and Its Impact on Offspring in Perinatal Demise Associated With Gestational Diabetes Mellitus: An Autopsy Case Series.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a common metabolic disorder linked to adverse pregnancy outcomes. Recent research indicates that HbA1c is reliable in detecting maternal glycemia during the first trimester but may underestimate glucose intolerance in the late second to third trimesters. Therefore, it is reasonable to hypothesize that mothers with GDM, despite apparently normal HbA1c levels in the third trimester, may give birth to infants displaying characteristic features often seen in infants of diabetic mothers with suboptimal glycemic control. This study aimed to describe a case series of autopsy cases involving stillborn or deceased neonates delivered in the third trimester to mothers diagnosed with GDM and having normal HbA1c levels at or around the time of delivery. The primary focus was on identifying and documenting the characteristic features commonly associated with "infants of diabetic mothers" with suboptimal glycemic control in this series of cases. MATERIALS AND METHODS: We conducted a retrospective review of autopsy reports from our institution spanning 7.5 years. The study included cases that met the following criteria: (1) stillborn or infants who died in the early neonatal period, delivered in the third trimester; (2) mothers diagnosed with GDM; (3) normal maternal HbA1c levels of ≤6.1% at or around the time of delivery; (4) birthweight or femoral length exceeding the 90th percentile for gestational age; and (5) absence of genetic aberrations. We also examined these cases for other characteristic features associated with "infants of diabetic mothers." RESULTS: Ten autopsy cases met our inclusion criteria, including 9 stillbirths and 1 neonatal death. Gestational age at delivery ranged from 32 to 39 weeks (mean: 35.7 weeks). Femoral length exceeded the 90th percentile in all cases, and 6 cases had birthweights above the 90th percentile. Puffy facies were observed in 6 cases. Among the 9 cases with complete autopsies including internal examination, 6 exhibited excess adipose tissue, 4 had cardiomegaly, and 3 showed pancreatic islet hyperplasia. Hypoxic-ischemic encephalopathy was detected in 7 cases. No structural abnormalities were noted. DISCUSSION: Our findings demonstrated that fetuses and neonates born to mothers with apparently normal HbA1c levels in the third trimester could still display characteristic features commonly observed in infants of diabetic mothers with poor glycemic control, also known as "infants of diabetic mothers." This study underscores the potential of third-trimester maternal HbA1c measurements to underestimate maternal glycemia and its consequential impact on fetal development, as well as the subsequent manifestation of features of "infants of diabetic mothers."

C4d Staining Is Present in Normal Placentas From Pregnancies Prior to Pregnancy Loss Associated With Chronic Histiocytic Intervillositis and Is Reduced by Immunomodulatory Therapy in Subsequent Pregnancies.

INTRODUCTION: Chronic histiocytic intervillositis (CHI) is associated with adverse pregnancy outcomes and high recurrence risk. Recent studies suggest that CHI may represent a host-vs-graft rejection, and that C4d immunostain can be used as a marker for complement activation and antibody-mediated rejection in the CHI. MATERIALS AND METHODS: This retrospective cohort study focused on 5 fetal autopsy cases associated with CHI (5 index cases) from 5 women. We analyzed placentas from the index cases (fetal autopsy cases associated with CHI) and placentas from the women's previous and subsequent pregnancies. We assessed the presence and extent of CHI and C4d immunostaining in these placentas. We evaluated each available placenta and graded the severity of CHI as either <50% or ≥50%. Additionally, we conducted C4d immunostaining on one representative section from each placenta and graded the staining levels as follows: 0+ for staining <5%; 1+ for staining between 5% and <25%; 2+ for staining between 25% and <75%; and 3+ for staining ≥75%. RESULTS: Three of the 5 women had pregnancies prior to their index cases (fetal autopsy cases associated with CHI). Despite the absence of CHI in their initial pregnancies, the placentas displayed positive C4d staining with grades of 1+, 3+, and 3+, respectively. These results suggest the presence of complement activation and antibody-mediated rejection in placentas from their prior pregnancies without CHI. Three of the 5 women received immunomodulatory therapy after experiencing pregnancy losses associated with CHI. After treatment, 2 of these women had live births at 35 and 37 gestational weeks, respectively, while the third had a stillbirth at 25 gestational weeks. The severity of CHI and the degree of C4d staining in the placentas decreased in all 3 cases following immunomodulatory therapies. Specifically, the level of C4d staining decreased from 3+ to 2+, 2+ to 0+, and 3+ to 1+ in these 3 cases, respectively. DISCUSSION: In women with a history of recurrent pregnancy loss associated with CHI, C4d immunostaining was present in the placentas from their previous non-CHI pregnancies, suggesting activation of the classical complement pathway and antibody-mediated reaction in their prior non-CHI pregnancies before the development of CHI in subsequent pregnancies. Immunomodulatory therapy may improve pregnancy outcomes by reducing complement activation, as shown by the reduction of C4d immunopositivity in the placentas after immunomodulatory treatment. Although we believe that the study provides valuable insights, we acknowledge that there are limitations to the findings. Therefore, to further elucidate the pathogenesis of CHI, additional research efforts with a collaborative and multidisciplinary approach are necessary.

Time Required for Gross Examination of Routine Second and Third Trimester Singleton Placentas by Pathologists' Assistants.

INTRODUCTION: In both Canada and the United States, workload measurement for anatomic pathology is mainly based on complexity and clinical significance of specimens, with gross examination being a considerable contributor. While Pathologists' Assistants (PAs) play an increasing role in gross examination, there is little known regarding the time required for PAs to complete grossing tasks. This information is essential for effective staffing and workload management in pathology laboratories. The objective of our study was to determine the time required for PAs to gross second and third trimester singleton placentas in a large tertiary hospital with a significant perinatal pathology service. MATERIALS AND METHODS: For our study, 7 certified PAs each grossed a minimum of 10 second and third trimester singleton placentas using a standard placental grossing protocol, an electronic laboratory information system, and voice recognition dictation software. Placental specimens requiring photography, sampling for ancillary studies, or immediate pathologist's consultation were excluded. We calculated average and standard deviation of grossing times for each PA, overall average grossing time, and 95% confidence interval using a mixed linear regression model. We analyzed the impact of PA job experience, degree obtained, and number of blocks prepared on overall average in a multivariate analysis. RESULTS: The mean grossing times for each PA ranged from 11.0 (standard deviation [sd] = 2.0) to 17.8 (sd = 4.5) minutes. The overall average grossing time was 14.5 minutes, with a 95% confidence interval of 11.7 to 17.3 minutes. In multivariate analysis, an increase in the number of blocks prepared was significantly associated with longer overall average grossing time. If 4 blocks were prepared consistently, the model predicted a slightly lower overall average of 13.3 minutes, with a 95% confidence interval of 10.9 to 15.7 minutes. DISCUSSION: To our knowledge, our study is the first to objectively report time required for PAs to perform gross examinations of routine second and third trimester singleton placentas. The methodology of our study is replicable and can be applied to other specimen types and laboratory settings. Previously, estimated grossing times for specimens were primarily based on retrospective surveys, which were susceptible to recall errors and subjectivity. However, our study demonstrates objective data collection is achievable. Furthermore, the data collected from this study offer valuable insights into the accuracy of previous and current pathology workload models for second and third trimester singleton placentas.

"Decoding MH"-A de-stigmatization campaign in the Hong Kong Police Force.

Police officers are under high level of stress given the intense and emergent work nature. If left untreated, their mental wellbeing would be at risk and work performance compromised. However, mental health stigma is common among police officers and is perpetuated by factors like police cultures emphasizing toughness and self-reliance. In view of this, since 2016, the Hong Kong Police Force had launched a holistic campaign for Force members which was the first among law enforcement organizations in Hong Kong, aiming to reduce stigma, by enhancing mental health knowledge and decreasing negative attitudes and behaviors towards mental health issues. The programme incorporated standardised trainings of the Mental Health First Aid course with examples modified to the local police context, and psychoeducation via the use of digital medium and sharing by public figures. Positive feedback was received. It was foreseen that the campaign effects would increase Force members' awareness of their mental health, encourage help-seeking and facilitate officers' decision making when encountering crises in the community.

Substantial Decline in Invasive Pneumococcal Disease During Coronavirus Disease 2019 Pandemic in Hong Kong.

Compared with other countries, a more substantial decrease in the incidence of invasive pneumococcal disease was observed in Hong Kong, which is most likely attributable to the proactive mass adoption of face masks by the public. Human behavioral changes, particularly mask wearing, should be considered as an additional preventive strategy against invasive pneumococcal disease.

In Vitro Susceptibility of Typhoidal, Nontyphoidal, and Extended-Spectrum-ß-Lactamase-Producing Salmonella to Ceftolozane/Tazobactam.

Both typhoidal and nontyphoidal salmonellae are included in the top 15 drug-resistant threats described by the U.S. Centers for Disease Control and Prevention. There is an urgent need to look for alternative antibiotics for the treatment of Salmonella infections. We used the broth microdilution test to examine the in vitro susceptibilities of typhoidal and nontyphoidal salmonellae, including isolates positive for extended-spectrum ß-lactamase (ESBL), to ceftolozane/tazobactam and six other antibiotics. Of the 313 (52 typhoidal and 261 nontyphoidal) Salmonella isolates tested, 98.7% were susceptible to ceftolozane/tazobactam. Based on the overall MIC50/90 values, Salmonella isolates were more susceptible to ceftolozane/tazobactam (0.25/0.5 mg/L) than all the comparator agents: ampicillin (≥64/≥64 mg/L), levofloxacin (0.25/1 mg/L), azithromycin (4/16 mg/L), ceftriaxone (≤0.25/4 mg/L), chloramphenicol (8/≥64 mg/L), and trimethoprim/sulfamethoxazole (1/≥8 mg/L). Comparison of the activities of the antimicrobial agents against nontyphoidal Salmonella isolates according to their serogroups showed that ceftolozane/tazobactam had the highest activity (100%) against Salmonella serogroup D, G, I, and Q isolates, whereas the lowest activity (85.7%) was observed against serogroup E isolates. All 10 ESBL-producing Salmonella isolates (all nontyphoidal), of which 8 were CTX-M-55 producers and 2 were CTX-M-65 producers, were sensitive to ceftolozane/tazobactam, albeit with MIC50/90 values higher (1/2 mg/L) than those for non-ESBL producers (0.25/0.5 mg/L). In summary, our data indicate that ceftolozane/tazobactam is active against most strains of both typhoidal and nontyphoidal salmonellae and also against ESBL-producing salmonellae.

ERS statement on paediatric long-term noninvasive respiratory support.

Long-term noninvasive respiratory support, comprising continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV), in children is expanding worldwide, with increasing complexities of children being considered for this type of ventilator support and expanding indications such as palliative care. There have been improvements in equipment and interfaces. Despite growing experience, there are still gaps in a significant number of areas: there is a lack of validated criteria for CPAP/NIV initiation, optimal follow-up and monitoring; weaning and long-term benefits have not been evaluated. Therapeutic education of the caregivers and the patient is of paramount importance, as well as continuous support and assistance, in order to achieve optimal adherence. The preservation or improvement of the quality of life of the patient and caregivers should be a concern for all children treated with long-term CPAP/NIV. As NIV is a highly specialised treatment, patients are usually managed by an experienced paediatric multidisciplinary team. This statement written by experts in the field of paediatric long-term CPAP/NIV aims to emphasise the most recent scientific input and should open up new perspectives and research areas.

Genotype-related respiratory progression in Duchenne muscular dystrophy-A multicenter international study.

INTRODUCTION/AIMS: Mutations amenable to skipping of specific exons have been associated with different motor progression in Duchenne muscular dystrophy (DMD). Less is known about their association with long-term respiratory function. In this study we investigated the features of respiratory progression in four DMD genotypes relevant in ongoing exon-skipping therapeutic strategies. METHODS: This was a retrospective longitudinal study including DMD children followed by the UK NorthStar Network and international AFM Network centers (May 2003 to October 2020). We included boys amenable to skip exons 44, 45, 51, or 53, who were older than 5 years of age and ambulant at first recorded visit. Subjects who were corticosteroid-naive or enrolled in interventional clinical trials were excluded. The progression of respiratory function (absolute forced vital capacity [FVC] and calculated as percent predicted [FVC%]) was compared across the four subgroups (skip44, skip45, skip51, skip53). RESULTS: We included 142 boys in the study. Mean (standard deviation) age at first visit was 8.6 (2.5) years. Median follow-up was 3 (range, 0.3-8.3) years. In skip45 and skip51, FVC% declined linearly from the first recorded visit. From the age of 9 years, FVC% declined linearly in all genotypes. Skip44 had the slowest (2.7%/year) and skip51 the fastest (5.9%/year) annual FVC% decline. The absolute FVC increased progressively in skip44, skip45, and skip51. In skip53, FVC started declining from 14 years of age. DISCUSSION: The progression of respiratory dysfunction follows different patterns for specific genotype categories. This information is valuable for prognosis and for the evaluation of exon-skipping therapies.

An fMRI study of cognitive planning before and after symptom provocation in pediatric obsessive-compulsive disorder.

BACKGROUND: Pediatric obsessive-compulsive disorder (OCD) has been associated with poorer planning in laboratory, school and home settings. It is unclear whether this impairment is a standalone cognitive issue or the result of OCD symptoms. No study has examined the influence of provoked distress on planning performance and neural correlates in pediatric OCD. METHODS: Before and after a symptom provocation task, youth with OCD (n = 23; 9 boys; mean age ± standard deviation 15.1 ± 2.6 years) and matched healthy controls (n = 23) completed the Tower of London task during functional MRI scanning. RESULTS: During planning, participants with OCD recruited the left superior frontal gyrus to a greater extent than healthy controls after symptom provocation (group × time point interaction; t 44 = 5.22, p < 0.001). In a seeded, region of interest-constrained, functional connectivity analysis, we identified greater connectivity between the left superior frontal gyrus and the right middle frontal gyrus, left precuneus and left inferior parietal lobule in participants with OCD than healthy controls. We also identified greater connectivity between the right amygdala and right medial frontal gyrus in patients with OCD than healthy controls, but only before symptom provocation. LIMITATIONS: The fixed-order design of the study and the number of participants taking medication (n = 20) should be noted. CONCLUSION: Participants with OCD demonstrated greater amygdalar-cortical connectivity before symptom provocation, while sustaining greater recruitment and connectivity of task-related planning areas throughout the task. These results suggest that brain activity and connectivity is altered after symptom provocation, in the absence of impaired planning performance.

Patient Experiences at California Crisis Pregnancy Centers: A Mixed-Methods Analysis of Online Crowd-Sourced Reviews, 2010-2019.

OBJECTIVES: Crisis pregnancy centers (CPCs) are nonprofit antiabortion organizations that claim provision of pregnancy resources. With the Reproduction Freedom, Accountability, Comprehensive Care, and Transparency Act repealed, CPCs are no longer mandated to share information on state-funded family planning and abortion services. As patients increasingly seek healthcare guidance online, we evaluated crowd-sourced reviews of CPCs using the social networking site Yelp. METHODS: CPCs were identified with the CPC Map, a geo-based location resource. Of California's 145 CPCs, 84% had Yelp pages, and 619 reviews (2010-2019) were extracted. Thematic codes were individually applied to 220 excerpts and then analyzed in detail using thematic analysis to capture emergent themes related to motivations for and experiences of CPCs. To ensure thematic saturation, we applied a natural language-processing technique called the meaning extraction method to computationally derive themes of discussion from all of the extracted posts. RESULTS: Motivations to seek care from CPCs included pregnancy confirmation, gaps in healthcare coverage, parenting and emotional support, and abortion care. A review of experiences reveal that CPC faith-based practice garnered both positive- and negative-based experiences. Reviewers also articulated inaccurate medical information, lack of transparency, and reduced options at CPCs. CONCLUSIONS: This is the first study to analyze California CPCs using a social media platform. Pregnant patients turn to social media to share experiences about pregnancy resources, to find healthcare providers, and to increase transparency of services. This content provides valuable insight into the concerns of pregnant patients and offers an intimate view of California CPCs at a time when no federal regulations are in place.

Clinical features, disease activity and outcomes of Malaysian children with paediatric systemic lupus erythematosus: A cohort from a tertiary centre.

BACKGROUND: Paediatric systemic lupus erythematosus is a rare autoimmune disease with a wide spectrum of clinical presentation in different populations. We present a cohort of paediatric systemic lupus erythematosus in Malaysia where the disease features and outcomes are still largely unknown. METHODS: A retrospective review of all paediatric systemic lupus erythematosus patients with at least 6 months follow-up at Selayang Hospital from 2004 to 2016. Epidemiological, clinical and outcome data were collected and analysed. RESULTS: A total of 141 paediatric systemic lupus erythematosus patients, 87.9% females, were followed up for a median 6.3 years (interquartile range 3.6-9.0). The median age at diagnosis was 10.8 years (interquartile range 9.0-12.0 years), positive family history of systemic lupus erythematosus was present in 12.1% and the majority (61.7%) were of Malay ethnicity. Common presentations included fever (87.2%), vasculitic rash (72.3%) and lethargy (69.5%). At diagnosis, leukopenia (51.1%), thrombocytopenia (41.8%) and cutaneous lupus (56%) predominate with significant renal involvement (39.7%). Renal (45.4%), liver (26%) and the central nervous system (17%) were important major organs involved during the course of the disease. At diagnosis, almost all (99.3%) patients had high disease activity (mean Systemic Lupus Erythematosus Disease Activity Index score 20.1 ± 9.6). The majority (62.4%) achieved remission or low disease activity after 6 months, maintained over the next 10 years. Damage occurred early (39.1% at 1 year) and increased with time. Ocular damage was the most common side effect (29%) and was predominantly corticosteroid related (93%). Growth retardation was significant (38.2%) with no gonadal failure or secondary malignancies. End-stage renal disease occurred in 3.1% patients whereas 53.1% had sustained renal remission. Overall mortality was 1.4%. CONCLUSION: Despite high disease activity at diagnosis, the majority had good sustained response to treatment with low overall mortality. However, there was progressive accrual of organ damage, highlighting the need for further research and refinements into therapies for paediatric systemic lupus erythematosus.

The unhealthy = tasty belief is associated with BMI through reduced consumption of vegetables: A cross-national and mediational analysis.

Obesity is one of the greatest public health challenges of modern times and its prevalence is increasing worldwide. With food so abundant in developed countries, many people face a conflict between desires for short-term taste and the goal of long-term health, multiple times a day. Recent research suggests that consumers often resolve these conflicts based on their lay beliefs about the healthiness and tastiness of food. Consequently, such lay beliefs can play critical roles not just in food choice but also weight gain. In this research, we show, across six countries and through mediation analysis, that adults who believe that tasty food is unhealthy (the Unhealthy = Tasty Intuition, or "UTI"; Raghunathan, Naylor, & Hoyer 2006) are less likely to consume healthy food, and thereby have a higher body mass index (BMI). In Study 1, we conducted a cross-sectional survey in five countries (Australia, Germany, Hong Kong, India, and the UK), and found that greater strength of belief in UTI was associated with higher BMI, and this relationship was mediated by lower consumption of fruits and vegetables. The observed patterns largely converged across the sampled Western and Asian-Pacific countries. In Study 2, we teased apart the mediating role of vegetable versus fruit consumption and also addressed the issue of reversed causality by predicting BMI with a measure of UTI belief taken 30 months previously. We found that vegetable consumption, but not fruit consumption, mediated the association between UTI belief and BMI. Our findings contribute to the literature by showing how lay beliefs about food can have pervasive and long-lasting effects on dietary practices and health worldwide. Implications for public policy and health practitioners are discussed.

Massive ascites and severe pulmonary hypoplasia in a premature infant with meconium peritonitis and congenital cytomegalovirus infection.

Background: Meconium peritonitis (MP) is an infrequent prenatal complication. Association between MP and pulmonary hypoplasia has never been reported. Case Report: A female infant with antenatally diagnosed MP and ascites was delivered at 36 gestational weeks. She died shortly after birth due to pulmonary insufficiency. Autopsy confirmed the presence of MP and ascites, and additionally revealed intestinal malrotation, volvulus, necrosis and perforation, and pulmonary hypoplasia. Congenital cytomegalovirus (CMV) infection was also noted. This was an unexpected finding as the mother was tested negative for CMV IgM at 26 gestational weeks after sonographic detection of fetal ascites. Conclusions: This is the first reported case of lethal pulmonary hypoplasia in a neonate with MP-associated ascites complicated by congenital CMV infection. This case illustrates that a negative maternal CMV IgM might not be sufficient to rule out congenital CMV, and that a concomitant infectious etiology should always be considered even when a primary cause for fetal ascites (e.g., MP in this case) is identified.

Atypical Prenatal Ultrasound Presentation and Neuropathological Findings in a Neonate With Alpha Thalassemia Major: A Case Report.

Alpha thalassemia major is a hemoglobinopathy caused by the inactivation or deletion of all 4 α-globin alleles. We describe a case of α-thalassemia major with atypical ultrasound and neuropathological findings. The mother had her first prenatal visit at 27 4/7 gestational weeks. Ultrasound revealed a hydropic fetus with multiple anomalies. However, the middle cerebral artery peak systolic velocity (MCA-PSV) suggested that the likelihood of fetal anemia was low. Given the poor prognosis of hydrops fetalis, the parents opted for termination of pregnancy. The neonate died shortly after birth. Autopsy revealed a markedly hydropic female infant with severe limb reduction defects and, in contrast to what was suggested by the prenatal MCA-PSV measurement, unequivocal signs of severe anemia. The brain showed diffuse white matter gliosis. Genetic testing subsequently identified HBA1 and HBA2 deletions, consistent with α-thalassemia major. This case highlights the potential pitfall of MCA-PSV, which is nowadays considered the gold standard for noninvasive detection of fetal anemia. In addition, this is 1 of 2 published case reports detailing neuropathological findings in a fetus or neonate with α-thalassemia major and the first to link α-thalassemia major with diffuse white matter gliosis.

Factors associated with high strain in caregivers of Alzheimer's disease (AD) in Malaysia.

A cross-sectional study design involving a total of 230 participants, recruited through Alzheimer's Disease Foundation Malaysia (ADFM), was adopted to access and correlate caregiver strain index (CSI) and resilience (RES) levels of the AD caregivers with various patients' and caregivers' factors. Findings revealed that 77.7% of caregivers had a high level of stress, and there was a significant negative correlation between RES and CSI (P < 0.001). Care recipients' physical function was negatively associated with CSI level. Caregivers' gender and employment status were not directly associated with CSI but were significantly associated with caregivers' RES level. Among the mediator variables, years of care was related to increase CSI and adult-children of AD patients experienced a higher level of caregiver strain compared to the other caregiver groups (P = 0.025). Thus, interventions to improve the family caregivers' RES level, and support for AD patients will be helpful in lowering the strains of AD caregivers.

A tricyclic pyrrolobenzodiazepine produced by Klebsiella oxytoca is associated with cytotoxicity in antibiotic-associated hemorrhagic colitis.

Cytotoxin-producing Klebsiella oxytoca is the causative agent of antibiotic-associated hemorrhagic colitis (AAHC). Recently, the cytotoxin associated with AAHC was identified as tilivalline, a known pentacyclic pyrrolobenzodiazepine (PBD) metabolite produced by K. oxytoca Although this assertion of tilivalline's role in AAHC is supported by evidence from animal experiments, some key aspects of this finding appear to be incompatible with toxicity mechanisms of known PBD toxins. We therefore hypothesized that K. oxytoca may produce some other uncharacterized cytotoxins. To address this question, we investigated whether tilivalline alone is indeed necessary and sufficient to induce cytotoxicity or whether K. oxytoca also produces other cytotoxins. LC-MS- and NMR-based metabolomic analyses revealed the presence of an abundant tricyclic PBD, provisionally designated kleboxymycin, in the supernatant of toxigenic K. oxytoca strains. Moreover, by generating multiple mutants with gene deletions affecting tilivalline biosynthesis, we show that a tryptophanase-deficient, tilivalline-negative K. oxytoca mutant induced cytotoxicity in vitro similar to tilivalline-positive K. oxytoca strains. Furthermore, synthetic kleboxymycin exhibited greater than 9-fold higher cytotoxicity than tilivalline in TC50 cell culture assays. We also found that the biosynthetic pathways for kleboxymycin and tilivalline appear to overlap, as tilivalline is an indole derivative of kleboxymycin. In summary, our results indicate that tilivalline is not essential for inducing cytotoxicity observed in K. oxytoca-associated AAHC and that kleboxymycin is a tilivalline-related bacterial metabolite with even higher cytotoxicity.

Molecular and functional characterization of tumor-induced factor (TIF): Hamster homolog of CXCL3 (GROγ) displays tumor suppressive activity.

Previously our lab has created a mouse ovarian xenograft model of copy number variation (CNV)-mediated G protein-coupled receptor (GPCR) MAS-driven tumorigenesis, and RNA profiling identified a putative chemokine tumor-induced factor (Tif). Sequence analysis and chemotactic study suggested that Tif was likely to be a hamster homolog of human GROγ (CXCL3) [IJC 125 (2009): 1316-1327]. In the present study, we report the molecular and functional characterization of the Tif gene. Genomic study of CHO-K1 cells indicated that Tif gene consisted of 4 exons, characterized with an antisense B1 element which is embedded in the fourth exon. Two Tif transcripts were identified which shared identical sequences except that a string of 71-nt derived from the antisense B1 element was deficient in the shorter transcript. Of interests, B1-like RNA ladder was detected in xenografts. Functional studies showed that TIF induced chemotaxis and neovessel formation. Pharmacological studies suggested that TIF activated Gi-coupled CXCR2 and induced both calcium mobilization and ERK1/2 phosphorylation, and suppressed forskolin-stimulated cAMP accumulation. In addition, secreted matured TIF functioned as an autocrine factor and promoted anchorage-independent growth. Unexpectedly, TIF delayed the onset of tumor formation, possibly via suppressing proliferation of stromal fibroblasts. However, TIF did not exert any inhibitory effect on tumor growth. Potentially, TIF could be used for preventing cancer relapse.

Tsukamurella ocularis sp. nov. and Tsukamurella hominis sp. nov., isolated from patients with conjunctivitis in Hong Kong.

Three bacterial strains, HKU63T, HKU64 and HKU65T, were isolated from the conjunctival swabs of three patients with conjunctivitis in Hong Kong. The three strains were aerobic, Gram-stain-positive, catalase-positive, non-sporulating and non-motile bacilli and exhibited unique biochemical profiles distinguishable from closely related Tsukamurella species. 16S rRNA gene sequence analysis revealed that the three strains shared identical sequences with each other, being most closely related to Tsukamurella tyrosinosolvens and Tsukamurella pulmonis, sharing 99.9 % sequence identity. Sequence analysis of three additional housekeeping genes, groEL, secA and rpoB, revealed 100 % nucleotide sequence identity between HKU63T and HKU64, 94.2-97.0 % nucleotide sequence identities between HKU63T/HKU64 and HKU65T and the three strains shared 82.9-98.9 % sequence identities with other currently recognized Tsukamurella species. DNA-DNA hybridization confirmed that they were distinct from other known species of the genus Tsukamurella(23.0±4.2 to 50.7±3.7 % DNA-DNA relatedness), of which HKU63T and HKU64 represented the same species (≥95.2±4.8 % DNA-DNA relatedness) while HKU65T represented another species. Fatty acid, mycolic acid, cell-wall sugar and peptidoglycan analyses showed that they were typical of members of Tsukamurella. The G+C content of strains HKU63T, HKU64 and HKU65T were 71.3±1.9, 71.3±2.0 and 71.2±2.3 mol% (mean±sd; n=3), respectively. A novel species, Tsukamurella ocularis sp. nov. is proposed to accommodate strains HKU63T and HKU64, with HKU63T (=JCM 31969T=DSM 105034T) designated as the type strain whilst another novel species, Tsukamurella hominis sp. nov., is proposed to accommodate the third strain, HKU65T, which is designated as the type strain (=JCM 31971T=DSM 105036T).