Integration of temporal and spatial patterning generates neural diversity.

In the Drosophila optic lobes, 800 retinotopically organized columns in the medulla act as functional units for processing visual information. The medulla contains over 80 types of neuron, which belong to two classes: uni-columnar neurons have a stoichiometry of one per column, while multi-columnar neurons contact multiple columns. Here we show that combinatorial inputs from temporal and spatial axes generate this neuronal diversity: all neuroblasts switch fates over time to produce different neurons; the neuroepithelium that generates neuroblasts is also subdivided into six compartments by the expression of specific factors. Uni-columnar neurons are produced in all spatial compartments independently of spatial input; they innervate the neuropil where they are generated. Multi-columnar neurons are generated in smaller numbers in restricted compartments and require spatial input; the majority of their cell bodies subsequently move to cover the entire medulla. The selective integration of spatial inputs by a fixed temporal neuroblast cascade thus acts as a powerful mechanism for generating neural diversity, regulating stoichiometry and the formation of retinotopy.

Identification of enhancers that drive the spatially restricted expression of Vsx1 and Rx in the outer proliferation center of the developing Drosophila optic lobe.

Combinatorial spatial and temporal patterning of stem cells is a powerful mechanism for the generation of neural diversity in insect and vertebrate nervous systems. In the developing Drosophila medulla, the neural stem cells of the outer proliferation center (OPC) are spatially patterned by the mutually exclusive expression of three homeobox transcription factors: Vsx1 in the center of the OPC crescent (cOPC), Optix in the main arms (mOPC), and Rx in the posterior tips (pOPC). These spatial factors act together with a temporal cascade of transcription factors in OPC neuroblasts to specify the greater than 80 medulla cell types. Here, we identify the enhancers that are sufficient to drive the spatially restricted expression of the Vsx1 and Rx genes in the OPC. We show that removal of the cOPC enhancer in the Muddled inversion mutant leads to the loss of Vsx1 expression in the cOPC. Analysis of the evolutionarily conserved sequences within these enhancers suggests that direct repression by Optix may restrict the expression of Vsx1 and Rx to the cOPC and pOPC, respectively.

Investigating Barriers to Completion of Postpartum Tubal Ligation: A Retrospective Chart Review.

OBJECTIVES: To identify the completion rate for postpartum tubal ligation (PPTL) and predictors of noncompletion of PPTL in a central New Jersey population. METHODS: We conducted a retrospective chart review at a tertiary care center in New Jersey for patients delivering during an 18-month period. We used the electronic medical record to identify all of the patients who had documented desire for a PPTL at the time of admission. We calculated the rate of PPTL completion and identified predictors of completion and risk factors for noncompletion. We recorded any documented reasons for cancellation and choice of contraception after noncompletion. RESULTS: Of 626 women who requested PPTL on admission, 508 (81.2%) procedures were performed. The most common reasons for noncompletion were patient changing her mind (38.1%) and unknown/not documented (22.9%). Cesarean delivery was the strongest predictor of completion, with 93.4% completion among cesarean deliveries compared with 65.6% among vaginal deliveries (P < 0.01). Lack of insurance also was associated with noncompletion (P < 0.01). There was no difference in body mass index (P = 0.75), gravidity (P = 0.99), parity (P = 0.72), or high-risk status (P = 0.47) between completed and noncompleted PPTL. CONCLUSIONS: Cesarean delivery is a strong predictor of PPTL completion, most likely because of easier availability of the operating room, anesthesia, and ancillary staff. Body mass index, gravidity, and parity are not associated with PPTL completion. Future research should focus on exploring whether this association is system, provider, or patient dependent.

Binary cell fate decisions and fate transformation in the Drosophila larval eye.

The functionality of sensory neurons is defined by the expression of specific sensory receptor genes. During the development of the Drosophila larval eye, photoreceptor neurons (PRs) make a binary choice to express either the blue-sensitive Rhodopsin 5 (Rh5) or the green-sensitive Rhodopsin 6 (Rh6). Later during metamorphosis, ecdysone signaling induces a cell fate and sensory receptor switch: Rh5-PRs are re-programmed to express Rh6 and become the eyelet, a small group of extraretinal PRs involved in circadian entrainment. However, the genetic and molecular mechanisms of how the binary cell fate decisions are made and switched remain poorly understood. We show that interplay of two transcription factors Senseless (Sens) and Hazy control cell fate decisions, terminal differentiation of the larval eye and its transformation into eyelet. During initial differentiation, a pulse of Sens expression in primary precursors regulates their differentiation into Rh5-PRs and repression of an alternative Rh6-cell fate. Later, during the transformation of the larval eye into the adult eyelet, Sens serves as an anti-apoptotic factor in Rh5-PRs, which helps in promoting survival of Rh5-PRs during metamorphosis and is subsequently required for Rh6 expression. Comparably, during PR differentiation Hazy functions in initiation and maintenance of rhodopsin expression. Hazy represses Sens specifically in the Rh6-PRs, allowing them to die during metamorphosis. Our findings show that the same transcription factors regulate diverse aspects of larval and adult PR development at different stages and in a context-dependent manner.

Attitudes about marijuana use, potential risks, and legalization: a single-center survey of pregnant women.

OBJECTIVE: There is an association between recreational marijuana use in pregnancy and legalization. As more states legalize marijuana, its use in pregnancy may increase. The objective of this study was to evaluate pregnant women's knowledge and opinions about marijuana use, potential risks, and legalization. METHODS: A cross-sectional survey of pregnant women at a regional perinatal center in New Jersey was performed from January-December 2019. Pregnant subjects were invited to complete a voluntary, anonymous 23-question survey about marijuana use in pregnancy, potential risks, and legalization. Subjects were excluded if they could not read in English or Spanish. Survey questions were based on a 5-point Likert scale (1 = strongly agree, 2 = agree, 3 = neutral, 4 = disagree, and 5 = strongly disagree). Likelihood of agreeing or disagreeing with potential risks, with neutral responses as the reference, were estimated based on the relative risk (RR) (95% confidence interval [CI]). Associations were examined with prior tobacco/marijuana use and education level. RESULTS: During the study period, approximately 1133 consecutive patients were approached and 843 completed the study (74.4% response rate). The majority of participants were English-speaking, college educated, and employed. 204 (25.2%) reported prior marijuana use and 36 (4.5%) reported marijuana use during pregnancy. Overall, pregnant women had poor knowledge about potential risks of marijuana use in pregnancy. Although 234 (29.0%) patients were opposed to legalization, more than 90% of pregnant subjects indicated that they would be more likely to use marijuana in pregnancy if it were legalized. Associations of marijuana risks by prior tobacco use showed that nonsmokers had more awareness about risks. Nonsmokers had higher likelihood of agreeing that marijuana use may be harmful to a pregnancy (RR 1.41, 95% CI 1.12-1.76), may hurt the growth of a baby (RR 1.36, 95% CI 1.07-1.74), may cause preterm birth (RR 1.18, 95% CI 1.00-1.40), and may hurt a child's ability to learn (RR 1.20, 95% CI 0.95-1.51). Similar trends were observed for subjects who reported no prior marijuana use and for subjects with more than high school education. CONCLUSIONS: The majority of surveyed pregnant women demonstrated poor knowledge about the possible risks of marijuana in pregnancy and indicated that they would be more likely to use marijuana in pregnancy if it were legalized. As the use of marijuana increases, providers should focus on educating their patients about potential risks associated with marijuana use in pregnancy while additional research is needed to clarify associated risks.

Measuring compliance with a maternal fetal medicine obesity protocol: a secondary analysis.

BACKGROUND: Current trends in patient safety include protocolization of care with assumed compliance to the protocol by health care providers. In 2016, Schuster et al. found that implementation of a protocol for management of obese pregnant patients that included delivery by estimated due date (EDD) actually resulted in a decrease in cesarean deliveries. Although compliance to the aspect of the protocol that affected the primary outcome of that study was evaluated, compliance to every aspect of the protocol was not analyzed. Recent studies have suggested improvements in protocol outcomes when compliance is measured. Therefore, we sought to evaluate compliance to the other aspects of the Geisinger Maternal Fetal Medicine obesity protocol (MOP). OBJECTIVE: The objective of this study was to identify compliance with all elements of the Geisinger MOP and identify areas for potential improvement with regards to compliance. STUDY DESIGN: We performed a secondary analysis of the original study to evaluate compliance with protocol aspects during the study period. Ninety-seven patients were randomly selected for chart review. We assessed compliance with each element of the protocol, including early diabetes screening, fetal monitoring, growth ultrasounds, and delivery by EDD using simple statistics. RESULTS: By obesity class, compliance was as follows: for class I obese patients, compliance with early diabetes screening was 30% (12/36 patients). For class II obese patients, compliance with early diabetes screening was 57.1% (12/21 patients), and compliance with serial growth ultrasounds was 85.7% (18/21 patients). For class III obese patients, compliance with early diabetes screening was 74.4% (29/39 patients), compliance with serial growth ultrasounds was 84.6% (33/39 patients), compliance with nonstress tests was 82.0% (32/39 patients). Compliance with the recommendation for delivery by estimated due date was 95% (37/39 class III obese patients). CONCLUSION: Although compliance was excellent with delivery by EDD, compliance with remaining recommendations was low. This suggests additional interventions are important to maintain compliance.

Telemedicine for contraceptive counseling: Patient experiences during the early phase of the COVID-19 pandemic in New York City.

OBJECTIVE: During theCOVID-19 pandemic, many clinicians increased provision of telemedicine services. This study describes patient experiences with telemedicine for contraceptive counseling during the COVID-19 pandemic in New York City. STUDY DESIGN: This is a mixed-methods study which includes a web-based or phone survey and in-depth phone interviews with patients who had telemedicine visits for contraception. RESULTS: A total of 169 patients had eligible telemedicine visits between April 1 and June 30, 2020. Of these, 86 (51%) responded to the survey, and 23 (14%) participated in the interviews. We found that 86% of survey respondents were very satisfied with the telemedicine visit, and 63% said it completely met their needs. A majority (73%) strongly agreed that these visits should be maintained after the COVID-19 pandemic, and half (51%) would be very likely to choose them over in-person visits. In-depth interviews highlighted the convenience of telemedicine, especially for those with work or parenting responsibilities. Although some patients had in-person visits after telehealth, many appreciated the counseling they received remotely, and found the subsequent in-person visits more efficient. Patients identified visits that do not require physical exams as ideal visits for telehealth, and some hoped that all or most of their future visits would be telehealth visits. Many patients (43%) expressed a preference for phone over video visits. CONCLUSIONS: Patients reported an overall positive experience with telemedicine visits for contraceptive counseling during the COVID-19 pandemic. They appreciated the convenience of telemedicine visits and valued the virtual counseling experience. IMPLICATIONS: Health care providers who initiated or expanded telemedicine services for contraceptive counseling during the COVID-19 pandemic should consider continuing to offer them after the pandemic. At the policy level, these findings favor expanding access to telemedicine and providing reimbursement for virtual visits, including telephone visits.

Considerations for management of interstitial ectopic pregnancies: two case reports.

BACKGROUND: Conventional treatment of interstitial pregnancies includes systemic methotrexate, direct methotrexate injection, wedge resection, or hysterectomy. We present two cases of interstitial pregnancies that were successfully managed by different minimally invasive surgical techniques. We also report the novel use of hysteroscopic urologic stone retrieval forceps in the transvaginal removal of persistent products of conception after systemic methotrexate for an interstitial pregnancy. CASE PRESENTATION: Case 1 was a 28-year-old gravida 1 white woman at 8 weeks gestation; she was diagnosed with a left interstitial pregnancy. After laparoscopic confirmation of the interstitial pregnancy, successful ultrasound-guided suction dilation and curettage was performed. Case 2 was a 33-year-old gravida 3 para 1021 (one term pregnancy, no preterm pregnancies, one ectopic pregnancy and one spontaneous miscarriage, and one living child) Hispanic woman with persistent products of conception after systemic methotrexate for a left interstitial pregnancy. She underwent hysteroscopic-guided removal of the persistent products of conception, which was possible due to novel use of urologic stone retrieval forceps. CONCLUSIONS: Successful minimally invasive treatment of interstitial pregnancies may be possible in certain cases. Collaboration between different specialties continues to be important for improving minimally invasive options.

MPS1 kinase as a potential therapeutic target in medulloblastoma.

Medulloblastoma is the most common type of malignant brain tumor that affects children. Although recent advances in chemotherapy and radiation have improved outcomes, high-risk patients perform poorly with significant morbidity. Gene expression profiling has revealed that monopolar spindle 1 (MPS1) (TTK1) is highly expressed in medulloblastoma patient samples compared to that noted in normal cerebellum. MPS1 is a key regulator of the spindle assembly checkpoint (SAC), a mitotic mechanism specifically required for proper chromosomal alignment and segregation. The SAC can be activated in aneuploid cancer cells and MPS1 is overexpressed in many types of cancers. A previous study has demonstrated the effectiveness of inhibiting MPS1 with small-molecule inhibitors, but the role of MPS1 in medulloblastoma is unknown. In the present study, we demonstrated that MPS1 inhibition by shRNA or with a small-molecule drug, NMS-P715, resulted in decreased cell growth, inhibition of clonogenic potential and induction of apoptosis in cells belonging to both the Shh and group 3 medulloblastoma genomic signature. These findings highlight MPS1 as a rational therapeutic target for medulloblastoma.