TORTS-FAMILY RELATIONSHIP-CHILD\u27S RIGHT TO RECOVER FOR ENTICEMENT OF PARENT FROM HOME

Plaintiff, a six year old girl, sued to recover damages alleged to have been sustained as a result of defendant\u27s enticing her mother from the family home. Plaintiff contended that as a child and member of the family she had a legally protected right to maintenance of the family relationship. Defendant answered that no tort had been committed, since no right in the plaintiff was recognized at common law and that to recognize such a right would amount to judicial legislation. From a judgment in favor of plaintiff, defendant appealed. Held, affirmed. Allowing a child a right of action against one enticing his parent from the home neither changes any rule of law nor upsets any precedent. Miller v. Monsen, (Minn. 1949) 37 N.W. (2d) 543

Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons

Elucidating how the brain's serotonergic network mediates diverse behavioral actions over both relatively short (minutes–hours) and long period of time (days–weeks) remains a major challenge for neuroscience. Our relative ignorance is largely due to the lack of technologies with robustness, reversibility, and spatio-temporal control. Recently, we have demonstrated that our chemogenetic approach (eg, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) provides a reliable and robust tool for controlling genetically defined neural populations. Here we show how short- and long-term activation of dorsal raphe nucleus (DRN) serotonergic neurons induces robust behavioral responses. We found that both short- and long-term activation of DRN serotonergic neurons induce antidepressant-like behavioral responses. However, only short-term activation induces anxiogenic-like behaviors. In parallel, these behavioral phenotypes were associated with a metabolic map of whole brain network activity via a recently developed non-invasive imaging technology DREAMM (DREADD Associated Metabolic Mapping). Our findings reveal a previously unappreciated brain network elicited by selective activation of DRN serotonin neurons and illuminate potential therapeutic and adverse effects of drugs targeting DRN neurons

Adenomatous Polyposis Coli Regulates Axon Arborization and Cytoskeleton Organization via Its N-Terminus

Conditional deletion of APC leads to marked disruption of cortical development and to excessive axonal branching of cortical neurons. However, little is known about the cell biological basis of this neuronal morphological regulation. Here we show that APC deficient cortical neuronal growth cones exhibit marked disruption of both microtubule and actin cytoskeleton. Functional analysis of the different APC domains revealed that axonal branches do not result from stabilized β-catenin, and that the C-terminus of APC containing microtubule regulatory domains only partially rescues the branching phenotype. Surprisingly, the N-terminus of APC containing the oligomerization domain and the armadillo repeats completely rescues the branching and cytoskeletal abnormalities. Our data indicate that APC is required for appropriate axon morphological development and that the N-terminus of APC is important for regulation of the neuronal cytoskeleton

90Y-clivatuzumab tetraxetan with or without low-dose gemcitabine: A phase Ib study in patients with metastatic pancreatic cancer after two or more prior therapies

AbstractBackgroundFor patients with metastatic pancreatic adenocarcinoma, there are no approved or established treatments beyond the 2nd line. A Phase Ib study of fractionated radioimmunotherapy was undertaken in this setting, administering 90Y-clivatuzumab tetraxetan (yttrium-90-radiolabelled humanised antibody targeting pancreatic adenocarcinoma mucin) with or without low radiosensitising doses of gemcitabine.MethodsFifty-eight patients with three (2–7) median prior treatments were treated on Arm A (N=29, 90Y-clivatuzumab tetraxetan, weekly 6.5mCi/m2doses×3, plus gemcitabine, weekly 200mg/m2 doses×4 starting 1week earlier) or Arm B (N=29, 90Y-clivatuzumab tetraxetan alone, weekly 6.5mCi/m2doses×3), repeating cycles after 4-week delays. Safety was the primary endpoint; efficacy was also evaluated.ResultsCytopaenias (predominantly transient thrombocytopenia) were the only significant toxicities. Fifty-three patients (27 Arm A, 26 Arm B, 91% overall) completed ⩾1 full treatment cycles, with 23 (12 Arm A, 11 Arm B; 40%) receiving multiple cycles, including seven (6 Arm A, 1 Arm B; 12%) given 3–9 cycles. Two patients in Arm A had partial responses by RECIST criteria. Kaplan–Meier overall survival (OS) appeared improved in Arm A versus B (hazard ratio [HR] 0.55, 95% CI: 0.29–0.86; P=0.017, log-rank) and the median OS for Arm A versus Arm B increased to 7.9 versus 3.4months with multiple cycles (HR 0.32, P=0.004), including three patients in Arm A surviving >1year.ConclusionsClinical studies of 90Y-clivatuzumab tetraxetan combined with low-dose gemcitabine appear feasible in metastatic pancreatic cancer patients beyond 2nd line and a Phase III trial of this combination is now underway in this setting

A rapid and sensitive system for recovery of nucleic acids from Mycobacteria sp. on archived glass slides

The field of diagnostics continues to advance rapidly with a variety of novel approaches, mainly dependent upon high technology platforms. Nonetheless much diagnosis, particularly in developing countries, still relies upon traditional methods such as microscopy. Biological material, particularly nucleic acids, on archived glass slides is a potential source of useful information both for diagnostic and epidemiological purposes. There are significant challenges faced when examining archived samples in order that an adequate amount of amplifiable DNA can be obtained. Herein, we describe a model system to detect low numbers of bacterial cells isolated from glass slides using (laser capture microscopy) LCM coupled with PCR amplification of a suitable target. Mycobacterium smegmatis was used as a model organism to provide a proof of principle for a method to recover bacteria from a stained sample on a glass slide using a laser capture system. Ziehl-Neelsen (ZN) stained cells were excised and catapulted into tubes. Recovered cells were subjected to DNA extraction and pre-amplified with multiple displacement amplification (MDA). This system allowed a minimum of 30 catapulted cells to be detected following a nested real-time PCR assay, using rpoB specific primers. The combination of MDA and nested real-time PCR resulted in a 30-fold increase in sensitivity for the detection of low numbers of cells isolated using LCM. This study highlights the potential of LCM coupled with MDA as a tool to improve the recovery of amplifiable nucleic acids from archived glass slides. The inclusion of the MDA step was essential to enable downstream amplification. This platform should be broadly applicable to a variety of diagnostic applications and we have used it as a proof of principle with a Mycobacterium sp. model system

FOLFIRINOX Induction Therapy for Stage 3 Pancreatic Adenocarcinoma

ABSTRACT Background. Reports show that FOLFIRINOX therapy for pancreatic ductal adenocarcinoma (PDAC) results in objective response rates two to threefold higher than those of other regimens. This study aimed to assess response and resection rates for locally unresectable (stage 3) patients initially treated with induction FOLFIRINOX. Methods. The institutional cancer database was queried for patients treated with induction FOLFIRINOX therapy between 2010 and 2013. Patients were included in the study if they were treated at the authors' institution for stage 3 PDAC (locally unresectable) that had been adjudicated at a weekly multidisciplinary tumor board. Results. The study identified 101 patients. The median age was 64 years (range 37-81 years), and the median followup period was 12 months (range 3-37 months). The patients received a median of six cycles (range 1-20 cycles) of induction FOLFIRINOX. No grade 4 or 5 toxicity was recorded. At the initial restaging (median of 3 months after diagnosis), 23 patients (23 %) had developed distant metastases, 15 patients (15 %) had undergone resection, and 63 patients (63 %) had proceeded to chemoradiation. In the group of 63 patients who had proceeded to chemoradiation (median of 9 months after diagnosis), an additional 16 patients (16 %) had undergone resection, and 5 patients (5 %) had developed metastases. A partial radiographic response was observed in 29 % of all the patients, which was associated with ability to perform resection (p = 0.004). The median overall survival time was 11 months for the group that progressed with FOLFIRINOX and 26 months for the group that did not progress. Conclusion. Nearly one third of the patients who had been initially identified as having stage 3 pancreatic carcinoma and had been treated with FOLFIRINOX responded radiographically and underwent tumor resection. A recently completed phase 3 randomized trial for stage 4 pancreatic ductal adenocarcinoma (PDAC) identified FOL-FIRINOX as superior to gemcitabine in terms of radiographic response together with improved progression-free and overall survival. 1 Patients who received FOLFIRINOX experienced a 32 % objective response rate (ORR) compared with 9 % in the gemcitabine arm of the study, which correlated with survival benefit (median overall and progression-free survival, 11 and 6 versus 7 and 3 months, respectively). Retrospective studies of patients with both borderline resectable PDAC (stages 1 and 2) and stage 3 disease (locally unresectable) also have suggested an ORR of approximately 30 % with FOLFIRINOX. 2,3 The reported ORR from non-FOLFIRINOX regimens has generally been in the range of 10 %, including the results of a phase

Urocortin-1 within the Centrally-Projecting Edinger-Westphal Nucleus Is Critical for Ethanol Preference

Converging lines of evidence point to the involvement of neurons of the centrally projecting Edinger-Westphal nucleus (EWcp) containing the neuropeptide Urocortin-1 (Ucn1) in excessive ethanol (EtOH) intake and EtOH sensitivity. Here, we expanded these previous findings by using a continuous-access, two-bottle choice drinking paradigm (3%, 6%, and 10% EtOH vs. tap water) to compare EtOH intake and EtOH preference in Ucn1 genetic knockout (KO) and wild-type (WT) mice. Based on previous studies demonstrating that electrolytic lesion of the EWcp attenuated EtOH intake and preference in high-drinking C57BL/6J mice, we also set out to determine whether EWcp lesion would differentially alter EtOH consumption in Ucn1 KO and WT mice. Finally, we implemented well-established place conditioning procedures in KO and WT mice to determine whether Ucn1 and the corticotropin-releasing factor type-2 receptor (CRF-R2) were involved in the rewarding and aversive effects of EtOH (2 g/kg, i.p.). Results from these studies revealed that (1) genetic deletion of Ucn1 dampened EtOH preference only in mice with an intact EWcp, but not in mice that received lesion of the EWcp, (2) lesion of the EWcp dampened EtOH intake in Ucn1 KO and WT mice, but dampened EtOH preference only in WT mice expressing Ucn1, and (3) genetic deletion of Ucn1 or CRF-R2 abolished the conditioned rewarding effects of EtOH, but deletion of Ucn1 had no effect on the conditioned aversive effects of EtOH. The current findings provide strong support for the hypothesis that EWcp-Ucn1 neurons play an important role in EtOH intake, preference, and reward

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research