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The present study aimed to clarify the alternations in alpha-fetoprotein (AFP), phosphorus (Ph), calcium (Ca), and metabolic hormones (Growth hormones (GH), insulin, and thyroid gland hormones) in singleton, twin, and triplet pregnancy in goats. Animals were examined for pregnancy ultrasonographically during mid-pregnancy (6-14 weeks of gestation), and were classified conferring to litter size into singleton (n =55), twin (n=25) and triple (n=6) pregnancy, and non-pregnant status (n=64). Blood samples (5 ml) were collected before ultrasound examination and serum was separated for analysis of alpha-fetoprotein, phosphorus, calcium, and GH, insulin, T3, and T4. The current data showed that the fetal numbers markedly influenced AFP, Ph, Ca, GH, insulin, T3 levels, but did not affect T4 and Ph/Ca ratio. AFP levels were higher in twin (P< 0.05) and triple (P< 0.001) bearing does than in non-pregnant does (56.00±5.00 and 87.00±1.90 vs 3.80±.051 ng/ml). Phosphorus and Ca levels declined with pregnancy, with the substantial decreased in multiple feti compared with non-pregnant does. Growth hormone imminently raised in twine and triple fetuses than non-pregnant does. Insulin levels elevated in triple compared to non- pregnant and singleton (P< 0.005). Serum free T3 levels were lower in single and twin bearing does than non-pregnancy. In conclusion, fetal number markedly influenced the dam metabolic profile and mineral homostatis through altering AFP and metabolic hormones levels during pregnancy in goats.

Obstructive sleep apnea (OSA) is associated with polycystic ovarian syndrome (PCOS), a common cause of infertility. Understanding predictors and outcomes of OSA in women with infertility may guide treatment.A descriptive cross-sectional survey was performed to assess OSA in women presenting to an infertility clinic using validated sleep questionnaires to assess sleep and fertility outcomes. An Infertile-C group (controls with male or tubal factors) and an Infertile-S group (unknown/other infertile causes) were analyzed to assess OSA risk and other sleep disorders (e.g., restless legs syndrome (RLS) and insomnia) with fertility outcomes (time to pregnancy, PCOS, irregular menstruation, and miscarriage).In 258 women, occurrences of OSA diagnosis (6%) and RLS (10%) were reported similar to women of child-bearing age in the general population. PCOS was unassociated with OSA risk. Predictors of OSA risk were BMI, insomnia symptoms, and sleep aid use. Obese women with high OSA risk were more likely to have other comorbidities (e.g., depression). In adjusted models, prior clinical OSA diagnosis was associated with miscarriage (odds ratio: 6.17 (1.24, 30.62), p = 0.026). RLS was associated with irregular menstruation (odds ratio: 3.73 (1.21, 11.53), p = 0.022).Similar to other populations, women with infertility and OSA risk have more health comorbidities and higher BMI and may present with insomnia symptoms. While the data are limited, this study supports the potential associations of OSA and miscarriage. Further work is needed to evaluate OSA in female infertility.

Introduction Kleine Levin Syndrome (KLS), or recurrent hypersomnia, is a rare sleep disorder characterized by recurrent episodes of severe hyper-somnolence lasting several days to several weeks. Because the etiology is unknown, treatment is mostly supportive. Some pharmacologic agents have been attempted to treat symptoms during episodes with limited success. Report of case(s) Patient is a 17 year-old with a history attention-deficit hyperactivity disorder and generalized anxiety disorder who presented to the clinic due to recurrent episodes of severe hypersomnolence associated with derealization and cognitive dysfunction during all episodes, anxiety of being alone, and other symptoms in some episodes such as altered taste affecting appetite, and binge eating. The patient was diagnosed with KLS and tracked episodes which lasted 11-12 days (average) with recurrence every 10-17 days. Labs, 72 hour EEG, MRI and MRA were largely unremarkable. The family declined trial of Lithium. Pharmacogenetic testing showed significant gene-drug interaction with duloxetine requiring higher drug dosage for effects. After psychiatry started duloxetine, the patient experienced a 7 month period without episodes. Then episodes recurred for unclear reason while on duloxetine but with slightly less duration (6-12 days) and shorter time between episodes. Duloxetine was discontinued due to lack of mood effects. Clarithromycin was trialed next for use during episodes without changes. Episodes were tracked for several months with some predictability. Duloxetine was restarted a second time after several months, and the patient showed mild improvement in event duration down to 8-11 days for a few months. Time between episodes also shortened to 8-10 days. Anxiety was only slightly reduced between and during the episodes, though they still continued to struggle with derealization and ability to focus during episodes that effected school and work functioning. Interestingly, they also started to have more insomnia between episodes while on duloxetine. Conclusion KLS is a rare disorder with limited data on effective treatments. To date, this is the first report of a prolonged brief KLS remission with duloxetine. Norepinephrine and serotonin modulation may limit episode duration. More research is needed to determine whether duloxetine can modulate the effects of KLS. Support (if any) None

Introduction The pivotal phase 3 REST-ON trial (NCT02720744) evaluated the efficacy and safety of once-nightly sodium oxybate (ON-SXB; FT218), an investigational extended-release formulation for treatment of adults with narcolepsy. In REST-ON, ON-SXB met its 3 coprimary endpoints: improvement in mean sleep latency on the Maintenance of Wakefulness test, Clinical Global Impression-Improvement rating (% much/very much improved), and number of weekly cataplexy attacks at all doses tested (P< 0.001 vs placebo). The safety profile of ON-SXB was consistent with that of immediate-release (IR) SXB. The ongoing RESTORE trial (NCT04451668) is an open-label/switch study evaluating the safety and tolerability of ON-SXB. Methods Participants aged ≥16 years with narcolepsy type 1 or 2 who completed the REST-ON trial, were on stable-dose (≥1 month) IR oxybate, or were oxybate-naive are eligible for RESTORE. Initial doses were 4.5 g/night or equivalent/closest to the previous total IR oxybate dose/night for those switching; incremental adjustments (1.5 g/week; maximum dose, 9 g/night) were allowed. Safety data for participants receiving ≥1 dose of ON-SXB as of 01 July 2022 are reported here. Results This analysis includes interim data from 180 participants (REST-ON participants, n=15 [8.3%]; oxybate-naive, n=35 [19.4%]; switch, n=130 [72.2%]). Most participants are white (n=150 [83.3%]) and female (n=122 [67.8%]); mean age is 35 years [range, 16–84]). Most participants who reported an adverse event (AE; n=105 [58.3%]) had AEs that were mild (61.9%) or moderate (32.3%) in severity. Three participants had serious AEs (abscess, deep vein thrombosis, rib fracture and pneumothorax); all were deemed unrelated to ON-SXB and all 3 participants continued in the study. Adverse drug reactions (ADRs; ie, AEs related/possibly related to study drug) were reported by 76 (42.2%) participants with 6 (3.3%) participants discontinuing ON-SXB owing to ADRs. ADRs occurring in ≥3% of participants were nausea (11.7%), somnolence (6.7%), headache (5%), enuresis (5%), somnambulism (3.9%), dizziness (3.9%), tremor (3.9%), and vomiting (3.3%). Conclusion Interim data from the RESTORE study indicate that ON-SXB is generally well tolerated with a low rate of discontinuation owing to ADRs. If granted final FDA approval, ON-SXB will offer adults with narcolepsy a once-at-bedtime oxybate treatment option. Support (if any) Avadel Pharmaceuticals

This study aimed to (1) identify the status of reproductive tract of repeat-breeder heifers (RBH) ultrasonography, as well as (2) determinethe variations in steroid hormones, oxidative stress biomarkers, and cell-free RNA in serum.These culled animals from400 heifers at the breeding stationwere examined ultrasonography, and whole blood samples were collected. Theultrasonic diagnosed heifers as paraovarian cyst (POC, n=18) associated with genital pathological conditionswere compared with groups of control heifers at follicular(n=6), luteal (n=6), and early pregnant (n=10). The POC appeared as anechoic circumscribed masses located nearby, but separated from the ovary. Follicular number, corpus luteum size, serum cell-free RNA, and ovarian steroids were not affected by POC, although dominant follicle size tended to be lower (P= 0.069)in POC withCL absence (POC-CL). Heifers with POC-CLhad lower MDA levels than pregnant ones. Buffaloes that had POC in the presence of CL (POC+CL) were found to have higher SOD activity than luteal and pregnant cases. Total serum proteinslevels recorded lower valuesin POC+CL compared to that in follicular phase. There was a significant positive relationship between POCsize, and GPx activity and CL size, but negative correlations with dominate follicles size. The POC might interfere with ovarian function, via alterations in antioxidant levels.

Background: Cryptosporidium parvum is a protozoan parasite of medical and veterinary importance that causes neonatal diarrhea in many vertebrate hosts. In this study, we evaluated the efficacy of an affinity-purified antigen as a C. parvum vaccine candidate using ileal and liver tissues of experimentally infected neonatal mice by immunohistochemical profiling and immune scoring of CD4, CD8, Caspase-3, and nuclear factor kappa B (NF-κB). This vaccine was prepared from the C. parvum oocyst antigen using immunoaffinity chromatography with cyanogen bromide-activated Sepharose-4B beads. Thirty neonatal mice were divided into three groups (10 mice/group): (1) nonimmunized noninfected, (2) nonimmunized infected (using gastric tubes with a single dose of 1×105 of C. parvum oocysts in 250 µl PBS solution 1 h before a meal) and (3) immunized (twice with 40 µg/kg of purified C. parvum antigen at 2-week intervals and then infected with 1×105 C. parvum oocysts simultaneously with the second group). After euthanizing the animals on the 10th day, post-infection, their ileal and liver tissues were collected and prepared for immunohistochemistry (IHC) staining to detect CD4, CD8, Caspase-3, and NF-κB levels, which are indicators for T helper cells, cytotoxic T cells, apoptosis, and inflammation, respectively. Results: The IHC results showed that CD4, CD8, Caspase-3, and NF-κB antibodies varied significantly (P <0.001) in both organs in all the groups. We also recorded high CD4 levels and low CD8 antibodies in the nonimmunized noninfected mice tissues, while the opposite was observed in the nonimmunized infected mice tissues. In the immunized infected mice, the CD4 level was higher than CD8 in both organs. While the Caspase-3 levels were higher in the ileal tissue of nonimmunized infected than immunized infected mice ileal tissues, the reverse was seen in the liver tissues of both groups. Furthermore, NF-κB expression was higher in the liver tissues of nonimmunized infected mice than in immunized infected mice tissues. Therefore, the IHC results and immune-scoring program revealed a significant difference (P <0.001) in the CD4, CD8, Caspase-3, and NF-κB antibody levels in both ileal and liver tissues of all mice groups, which might be necessary for immunomodulation in these tissues. Conclusions: The improvement observed in the immunized infected mice suggests that this vaccine candidate might protect against cryptosporidiosis.

This study was aimed to evaluate the yearly incidence of pediatric narcolepsy prior to and following the 2009 H1N1 pandemic and to evaluate seasonal patterns of narcolepsy onset and associations with H1N1 influenza infection in the United States. This was a multicenter retrospective study with prospective follow-up. Participants were recruited from members of the Pediatric Working Group of the Sleep Research Network including 22 sites across the United States. The main outcomes were monthly and yearly incident cases of childhood narcolepsy in the United States, and its relationship to historical H1N1 influenza data. A total of 950 participants were included in the analysis; 487 participants were male (51.3%). The mean age at onset of excessive daytime sleepiness (EDS) was 9.6 ± 3.9 years. Significant trend changes in pediatric narcolepsy incidence based on EDS onset (p

Caregivers frequently report poor quality of life (QOL) in children with sleep-disordered breathing (SDB). Our objective is to assess the correlation between caregiver- and child-reported QOL in children with mild SDB and identify factors associated with differences between caregiver and child report.Analysis of baseline data from a multi-institutional randomized trial.Pediatric Adenotonsillectomy Trial for Snoring, where children with mild SDB (obstructive apnea-hypopnea index3) were randomized to observation or adenotonsillectomy.The Pediatric Quality of Life Inventory (PedsQL) assessed baseline global QOL in participating children 5 to 12 years old and their caregivers. Caregiver and child scores were compared. Multivariable regression assessed whether clinical factors were associated with differences between caregiver and child report.PedsQL scores were available for 309 families (mean child age, 7.0 years). The mean caregiver-reported PedsQL score was higher at 75.2 (indicating better QOL) than the mean child-reported score of 67.9 (Caregiver- and child-reported global QOL in children with SDB was weakly correlated, more so for young children. In pediatric SDB, child-perceived QOL may be poorer than that reported by caregivers. Further research is needed to assess whether similar trends exist for disease-specific QOL metrics.

Introduction Restless Sleep Disorder (RSD) is characterized by frequent nocturnal movements of large muscle groups or a complaint of restless sleep by observers with associated daytime dysfunction.1 RSD, like other movement disorders of sleep, is associated with low iron stores.2 Children with RSD have increased NREM sleep instability and a propensity for parasomnia.2 No reports to date have demonstrated the use of iron therapy for parasomnia in patients with RSD. Furthermore, studies are limited in very young children with this disorder as they currently fall outside proposed diagnostic criteria.1 Report of Cases: A 2 year-old male presented to the sleep clinic with parental complaints of nightly sleep initiation and maintenance difficulty, mild snoring, restless sleep, episodes of sleepwalking and night terrors multiple times per week. Symptoms worsened over 6 months and were associated with daytime irritability and behavioral problems. Sleep quality measures assessed progress between visits: the PROMIS Sleep Disturbance (PROMIS SD) and Sleep Related Impairment (PROMIS SRI). Serum ferritin was initially 20ug/L. Polysmnogram demonstrated no significant sleep related breathing disorder, a large muscle group movement index of 14, periodic limb movement index of 3. Initial treatment included oral iron therapy, scheduled awakenings, and hypnotic dose melatonin. The sleep psychologist addressed limit setting and negative sleep associations with improved insomnia symptoms but parasomnia and restless sleep continued. The parent noted reduction in both movements and parasomnia frequency after one month of iron therapy. After a 3 month period on treatment, the parent reported complete cessation of the parasomnia, drastic reduction in restlessness, and near resolution of insomnia. Sleep quality measure PROMIS SD improved by 11, demonstrating reduced sleep disturbance. PROMIS SRI did not change. Ferritin level increased to 47ug/L. Conclusion RSD in a very young child with NREM parasomnia responded to oral iron therapy improving overall sleep quality. This case demonstrates the relationship between relative iron deficiency, RSD and associated parasomnia. Support (If Any) 1. DelRosso LM, Ferri R, Allen RP, et al. Consensus diagnostic criteria for a newly defined pediatric sleep disorder: restless sleep disorder(RSD).SleepMed.2020;75:335-340. 2. Leung W, Singh I, McWilliams S, Stockler S, Ipsiroglu OS. Iron deficiency and sleep - A scoping review. SleepMedRev.2020;51:101274