Rapid Innate Defensive Responses of Mice to Looming Visual Stimuli

Much of brain science is concerned with understanding the neural circuits that underlie specific behaviors. While the mouse has become a favorite experimental subject, the behaviors of this species are still poorly explored. For example, the mouse retina, like that of other mammals, contains ∼20 different circuits that compute distinct features of the visual scene [1 and 2]. By comparison, only a handful of innate visual behaviors are known in this species—the pupil reflex [3], phototaxis [4], the optomotor response [5], and the cliff response [6]—two of which are simple reflexes that require little visual processing. We explored the behavior of mice under a visual display that simulates an approaching object, which causes defensive reactions in some other species [7 and 8]. We show that mice respond to this stimulus either by initiating escape within a second or by freezing for an extended period. The probability of these defensive behaviors is strongly dependent on the parameters of the visual stimulus. Directed experiments identify candidate retinal circuits underlying the behavior and lead the way into detailed study of these neural pathways. This response is a new addition to the repertoire of innate defensive behaviors in the mouse that allows the detection and avoidance of aerial predators

High-Impact Mechanical Loading Increases Bone Material Strength in Postmenopausal Women-A 3-Month Intervention Study.

Bone adapts to loading in several ways, including redistributing bone mass and altered geometry and microarchitecture. Because of previous methodological limitations, it is not known how the bone material strength is affected by mechanical loading in humans. The aim of this study was to investigate the effect of a 3-month unilateral high-impact exercise program on bone material properties and microarchitecture in healthy postmenopausal women. A total of 20 healthy and inactive postmenopausal women (aged 55.6 ± 2.3 years [mean ± SD]) were included and asked to perform an exercise program of daily one-legged jumps (with incremental number, from 3×10 to 4×20 jumps/d) during 3 months. All participants were asked to register their performed jumps in a structured daily diary. The participants chose one leg as the intervention leg and the other leg was used as control. The operators were blinded to the participant's choice of leg for intervention. The predefined primary outcome was change in bone material strength index (BMSi), measured at the mid tibia with a handheld reference probe indentation instrument (OsteoProbe). Bone microstructure, geometry, and density were measured with high-resolution peripheral quantitative computed tomography (XtremeCT) at the ultradistal and at 14% of the tibia bone length (distal). Differences were analyzed by related samples Wilcoxon signed rank test. The overall compliance to the jumping program was 93.6%. Relative to the control leg, BMSi of the intervention leg increased 7% or 0.89 SD (p = 0.046), but no differences were found for any of the XtremeCT-derived bone parameters. In conclusion, a unilateral high-impact loading program increased BMSi in postmenopausal women rapidly without affecting bone microstructure, geometry, or density, indicating that intense mechanical loading has the ability to rapidly improve bone material properties before changes in bone mass or structure. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc

Ventromedial hypothalamic neurons control a defensive emotion state

Defensive behaviors reflect underlying emotion states, such as fear. The hypothalamus plays a role in such behaviors, but prevailing textbook views depict it as an effector of upstream emotion centers, such as the amygdala, rather than as an emotion center itself. We used optogenetic manipulations to probe the function of a specific hypothalamic cell type that mediates innate defensive responses. These neurons are sufficient to drive multiple defensive actions, and required for defensive behaviors in diverse contexts. The behavioral consequences of activating these neurons, moreover, exhibit properties characteristic of emotion states in general, including scalability, (negative) valence, generalization and persistence. Importantly, these neurons can also condition learned defensive behavior, further refuting long-standing claims that the hypothalamus is unable to support emotional learning and therefore is not an emotion center. These data indicate that the hypothalamus plays an integral role to instantiate emotion states, and is not simply a passive effector of upstream emotion centers

Comparison of Free Gingival Graft and Modified Apical Repositioned Flap Techniques to Create Attached Gingiva: Long-Term (2 Years) Retrospective Study

Objective: An ideal anatomical component for maintaining gingival health is the attached gingiva. Increasing the width of the attached gingiva can be achieved using the predictable surgical methods of the modified apically repositioned flap (MARF) and the free gingival graft (FGG). Methods: Fifteen (female) systemically and periodontally healthy patients were enrolled for this study. The treatment of a total of 21 teeth with recession in the lower jaw, absence of bone dehiscence, and attached gingiva ranging from a minimum of 0.5 mm to a maximum of 1.5 mm was conducted through FGG and modified apical positioned flap techniques. These procedures were randomly selected. Pocket depth on probing, gingival recession (GR), clinical attachment loss, bleeding index on probing, attached gingival width (AGW), keratinized tissue width and plaque index values were recorded before the surgical procedure and repeated at the 3rd month, 1st and 2nd years. Results: The changes in GR levels at baseline, 3 months, first and second year in both the FGG and MARF groups were statistically significant (p=0.001; p<0.05). The changes observed in AGW levels at baseline, 3 months, first and second year in both MARF and FGG groups were statistically significant (p=0.001; p<0.05). Conclusion: Both techniques have been shown to result in a statistically significant increase in the width of keratinized tissue and the amount of attached gingiva in the long term

Case report of radiation-induced lung injury with trastuzumab emtansine: the lung also matters

With an increase in the number of agents used concurrently with radiotherapy (RT), a new research area has emerged regarding toxicity. Here, we present a case of a 47-year-old woman presenting with radiation-induced lung injury (RILI) that occurred six months after the end of RT with concomitant and sequential use of trastuzumab-emtansine (T-DM1) with RT. The patient’s T-DM1 treatment was discontinued because of RILI. Antibiotic and methylprednisolone treatments were started. The steroid dose was gradually tapered and completely discontinued after full recovery. If new agents are used concurrently with RT, the toxicity profile of new agents should be kept in mind

Endovascular Stent Grafting for Aortic Arch Aneurysm in Aortoiliac Occlusive Disease following Aortic Arch Debranching and Aortobifemoral Reconstruction

Treatment of thoracic aortic aneurysms constitutes high mortality and morbidity rates despite improvements in surgery, anesthesia, and technology. Endovascular stent grafting may be an alternative therapy with lower risks when compared with conventional techniques. However, sometimes the branches of the aortic arch may require transport to the proximal segments prior to successful thoracic aortic endovascular stent grafting. Atherosclerosis is accounted among the etiology of both aneurysms and occlusive diseases that can coexist in the same patient. In these situations stent grafting may even be more complicated. In this report, we present the treatment of a 92-year-old patient with aortic arch aneurysm and proximal descending aortic aneurysm. For successful thoracic endovascular stent grafting, the patient needed an alternative route other than the native femoral and iliac arteries for the deployment of the stent graft. In addition, debranching of left carotid and subclavian arteries from the aortic arch was also required for successful exclusion of the thoracic aneurysm

Disease progression of WHIM syndrome in an international cohort of 66 pediatric and adult patients

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Roles of Retinal Circuits in the Innate Visual Behaviors of Mice

Much of brain science is concerned with understanding the neural circuits that underlie specific behaviors. While the mouse has become a favorite experimental subject, the behaviors of this species are still poorly explored, posing a challenge for understanding the neural basis for visual behaviors. We approach this problem first, by exploring the visual responses of mice of mice to visual stimuli, second by genetically ablating specific cell types in the retina and testing the effects on visual behaviors. We show that mice respond to the visual display of an approaching object by either initiating escape or by freezing for an extended period. We then use genetic means to ablate specific cell classes in the retina to dissect the roles of these classes in the looming avoidance behavior and two other visual behaviors: optokinetic reflex (OKR) and pupillary light reflex (PLR). We show that a class of cells including the alpha retinal ganglion cells are necessary for the looming avoidance behavior, while this class has minor roles in the pupillary constriction and optokinetic reflex. By contrast another cell class, starburst amacrine cells, are crucial for the optokinetic reflex and are dispensable for the looming avoidance and pupil reflexes. Our results suggest that mouse retina possesses neural circuits that are specialized for specific visual functions, such as avoiding an aerial predator, moving head to minimize retinal slip and constricting the pupil to limit light input to the retina.Biology, Molecular and Cellula