Mesenchymal stromal cells modulate infection and inflammation in the uterus and mammary gland.

The use of mesenchymal stromal cells (MSCs) is emerging as an efficacious and safe treatment for many infectious and non-infectious inflammatory diseases in human and veterinary medicine. Such use could be done to treat mastitis and metritis, which are the most common disease conditions affecting dairy cows leading to considerable economic losses and reduced animal welfare. Currently, both disease conditions are commonly treated using local and systemic administration of antibiotics. However, this strategy has many disadvantages including low cure rates and the public health hazards. Looking for alternative approaches, we investigated the properties of MSCs using in-vitro mammary and endometrial cell systems and in-vivo mastitis and metritis murine model systems. In-vitro, co-culture of mammary and uterus epithelial cells constructed with NF-kB reporter system, the master regulator of inflammation, demonstrated their anti-inflammatory effects in response to.LPS. In vivo, we challenge animals with field strains of mammary and utero pathogenic Escherichia coli and evaluated the effects of local and systemic application of MSC in the animal models. Disease outcome was evaluated using histological analysis, bacterial counts and gene expression of inflammatory markers. We show that MSC treatment reduced bacterial load in metritis and significantly modulated the inflammatory response of the uterus and mammary gland to bacterial infection. Most notably are the immune modulatory effects of remotely engrafted intravenous MSCs, which open new avenues to the development of MSC-based cell-free therapies.

Sporadic Burkitt Lymphoma Presenting with Middle Cranial Fossa Masses with Sphenoid Bony Invasion and Acute Pancreatitis in a Child.

Acute pancreatitis in children is usually due to infection, trauma, or anatomical abnormalities and is rarely due to obstruction from malignancy. Sporadic Burkitt lymphoma (BL) is an aggressive non-Hodgkin B-cell lymphoma that usually involves the bowel or pelvis, with isolated cases presenting as acute pancreatitis. We report a case of BL in a 12-year-old male presenting as acute pancreatitis with obstructive jaundice and a right middle cranial fossa mass invading the sphenoid bone. The common bile duct in this case was dilated to 21 mm in diameter on abdominal ultrasound and to 26 mm on magnetic resonance cholangiopancreatography (MRCP), significantly greater than any value reported in the literature for BL. Given the rapidly progressing nature of BL, we emphasize the importance of recognizing heterogeneous presentations of this disease to improve patient survival. We also conclude that it is important to consider malignancy in a child with acute pancreatitis, particularly in the presence of obstructive jaundice or multisystem involvement. Other Presentations. This case report has no prior publications apart from the abstract being accepted to the 2020 SIOP (International Society of Pediatric Oncology) meeting and 2020 ASPHO conference (canceled due to the COVID-19 pandemic) and subsequently published as an abstract only in Pediatric Blood and Cancer. We have also presented the abstract as a poster presentation at our institution's (NYU Langone Hospital-Long Island, previously known as NYU Winthrop) annual research day conference in 2020.

Seasonal variation of respiratory viral infections: a comparative study between children with cancer undergoing chemotherapy and children without cancer.

Respiratory viral infections (RVIs) affect children year-round, with seasonal-specific patterns. Pediatric oncology patients are uniquely vulnerable to infection, but whether this predisposes them to different patterns of RVIs than healthy children is unknown. There is also limited data on the impact of RVIs on cancer patients. We conducted a retrospective study of children ages 1-21 with cancer presenting to the clinic and emergency department (ED) and a randomly selected subset of patients without cancer presenting to the ED who had positive nasopharyngeal viral polymerase chain reactions at our institution from 2014 to 2019. Sixty-seven cancer patients (206 RVI episodes) and 225 pediatric non-cancer patients (237 RVI episodes) were included. Human rhino/enterovirus (HRE) was the most common infection in both groups in the spring, summer, and fall. In the winter, the most common RVI was influenza in cancer patients verses respiratory syncytial virus in non-cancer patients. On age-adjusted analysis, the likelihood of detecting coronavirus in the winter, HRE in the spring and fall, and parainfluenza in the summer was significantly greater in cancer patients (OR = 2.60, 2.52, 5.73, 3.59 respectively). Among cancer RVI episodes, 50% received parenteral antibiotics, 22% were severely neutropenic, 22% had chemotherapy delays for a median of six days, 16% were hospitalized, and 6% received intravenous immunoglobulin. We conclude that there are differences in the seasonal patterns of RVIs between children with and without cancer. RVIs also cause significant morbidity in children with cancer.

Haploseek: a 24-hour all-in-one method for preimplantation genetic diagnosis (PGD) of monogenic disease and aneuploidy.

PURPOSE: To develop an economical, user-friendly, and accurate all-in-one next-generation sequencing (NGS)-based workflow for single-cell gene variant detection combined with comprehensive chromosome screening in a 24-hour workflow protocol. METHODS: We subjected single lymphoblast cells or blastomere/blastocyst biopsies from four different families to low coverage (0.3×-1.4×) genome sequencing. We combined copy-number variant (CNV) detection and whole-genome haplotype phase prediction via Haploseek, a novel, user-friendly analysis pipeline. We validated haplotype predictions for each sample by comparing with clinical preimplantation genetic diagnosis (PGD) case results or by single-nucleotide polymorphism (SNP) microarray analysis of bulk DNA from each respective lymphoblast culture donor. CNV predictions were validated by established commercial kits for single-cell CNV prediction. RESULTS: Haplotype phasing of the single lymphoblast/embryo biopsy sequencing data was highly concordant with relevant ground truth haplotypes in all samples/biopsies from all four families. In addition, whole-genome copy-number assessments were concordant with the results of a commercial kit. CONCLUSION: Our results demonstrate the establishment of a reliable method for all-in-one molecular and chromosomal diagnosis of single cells. Important features of the Haploseek pipeline include rapid sample processing, rapid sequencing, streamlined analysis, and user-friendly reporting, so as to expedite clinical PGD implementation.

Microbiota manipulation for weight change.

Manipulation of the intestinal microbiota has been linked to weight changes and obesity. To explore the influence of specific agents that alter the intestinal flora on weight in different patient groups we conducted a meta-analysis of randomized controlled trials (RCTs) reporting on the effects of probiotics, prebiotics, synbiotics, and antibiotics on weight. We searched the Pubmed and Cochrane Library databases for trials on adults, children, and infants evaluating the effects of these substances on weight. Our primary outcome was weight change from baseline. Standardized mean differences (SMDs) with 95% confidence intervals were calculated. We identified and included 13 adult, 17 children, and 23 infant RCTs. Effects were opposite among adults and children, showing weight loss among adults (SMD -0.54 [-0.83, -0.25)) and minor weight gains among children (SMD 0.20 [0.04, 0.36]) and infants (SMD 0.30 [-0.01, 0.62]) taking mainly Lactobacillus probiotic supplements. Heterogeneity was substantial in the adult and infant analyses and could not be explained by intervention or patient characteristics. Azithromycin administration in children with pulmonary disease was associated with weight gain (SMD 0.39 [0.24, 0.54]), without heterogeneity. A high risk of selective reporting and attrition bias was detected across the studies, making it difficult to draw firm conclusions. Overall, our meta-analysis suggests that there may be a role for probiotics in promoting weight loss in adults and weight gain in children, however additional studies are needed. Though we cannot recommend antibiotic administration for weight manipulation, its use provides advantageous weight gain in children with cystic fibrosis and bronchiectasis.

Analysis of multiple positive feedback paradigms demonstrates a complete absence of LH surges and GnRH activation in mice lacking kisspeptin signaling.

Kisspeptin stimulates gonadotropin-releasing hormone (GnRH) neurons via the kisspeptin receptor, Kiss1r. In rodents, estrogen-responsive kisspeptin neurons in the rostral hypothalamus have been postulated to mediate estrogen-induced positive feedback induction of the preovulatory luteinizing hormone (LH) surge. However, conflicting evidence exists regarding the ability of mice lacking Kiss1r to display LH surges in response to exogenous hormones. Whether the discrepancy reflects different mouse strains used and/or utilization of different surge-induction paradigms is unknown. Here, we tested multiple hormonal paradigms in one Kiss1r knockout (KO) model to see which paradigms, if any, could generate circadian-timed LH surges. Kiss1r KO and wild-type (WT) females were ovariectomized, given sex steroids in various modes, and assessed several days later for LH levels in the morning or evening (when surges occur). Serum LH levels were very low in all morning animals, regardless of genotype or hormonal paradigm. In each paradigm, virtually all WT females displayed clear LH surges in the evening, whereas none of the KO females demonstrated LH surges. The lack of LH surges in KO mice reflects a lack of GnRH secretion rather than diminished pituitary responsiveness from a lifetime lack of GnRH exposure because KO mice responded to GnRH priming with robust LH secretion. Moreover, high cfos-GnRH coexpression was detected in WT females in the evening, whereas low cfos-GnRH coexpression was present in KO females at all time points. Our findings conclusively demonstrate that WT females consistently display LH surges under multiple hormonal paradigms, whereas Kiss1r KO mice do not, indicating that kisspeptin-Kiss1r signaling is mandatory for GnRH/LH surge induction.

Endoreduplication preferentially occurs at the proximal side of the abscission zone during abscission of tomato leaf.

Endoreduplication is a cell cycle variant in which multiple rounds of DNA replication occur without subsequent mitosis, resulting in polyploid cells. Although cells with endoreduplicated nuclei were ubiquitously distributed throughout the abscission zone (AZ) of tomato leaf before abscission induction by ethylene, endoreduplication was detected mostly on the proximal side of the AZ after induction. The possible association between endoreduplication and intensive membrane trafficking in cells at the proximal side of the AZ is discussed.