Triciribine attenuates pathological neovascularization and vascular permeability in a mouse model of proliferative retinopathy.

Proliferative retinopathies are the leading cause of irreversible blindness in all ages, and there is a critical need to identify novel therapies. We investigated the impact of triciribine (TCBN), a tricyclic nucleoside analog and a weak Akt inhibitor, on retinal neurovascular injury, vascular permeability, and inflammation in oxygen-induced retinopathy (OIR). Post-natal day 7 (P7) mouse pups were subjected to OIR, and treated (i.p.) with TCBN or vehicle from P14-P16 and compared with age-matched, normoxic, vehicle or TCBN-treated controls. P17 retinas were processed for flat mounts, immunostaining, Western blotting, and qRT-PCR studies. Fluorescein angiography, electroretinography, and spectral domain optical coherence tomography were performed on days P21, P26, and P30, respectively. TCBN treatment significantly reduced pathological neovascularization, vaso-obliteration, and inflammation marked by reduced TNFα, IL6, MCP-1, Iba1, and F4/80 (macrophage/microglia markers) expression compared to the vehicle-treated OIR mouse retinas. Pathological expression of VEGF (vascular endothelial growth factor), and claudin-5 compromised the blood-retinal barrier integrity in the OIR retinas correlating with increased vascular permeability and neovascular tuft formation, which were blunted by TCBN treatment. Of note, there were no changes in the retinal architecture or retinal cell function in response to TCBN in the normoxia or OIR mice. We conclude that TCBN protects against pathological neovascularization, restores blood-retinal barrier homeostasis, and reduces retinal inflammation without adversely affecting the retinal structure and neuronal function in a mouse model of OIR. Our data suggest that TCBN may provide a novel therapeutic option for proliferative retinopathy.

Sponsorship bias in oncology cost effectiveness analysis.

OBJECTIVES: Cost effectiveness analysis (CEA) has been increasingly used to inform cancer treatment coverage policy making worldwide. The primary objective of this study was to assess the association between industry sponsorship and CEA results in oncology. STUDY DESIGN AND SETTING: All CEAs in oncology used incremental cost per quality-adjusted life year (QALY) as health effect identified from the Tufts CEA Registry since 1976 was analyzed. Descriptive analyses were performed to present and compare the characteristics of CEA funded by industry and non-industry. Robust logistic regression was performed to assess the relationship between the industry sponsorship and cost effective conclusion over a wide range of threshold values. RESULTS: A total of 1537 CEAs in oncology published from 1976 to 2021 were included. There were 387 (25.2%) with the industry sponsorship. CEAs sponsored by the industry were more likely to report ICERs below $50,000/QALY (adjusted odds ratio (OR), 1.91, 95% confidence interval (CI), 1.45-2.51, P < 0.001), $100,000/QALY (2.74, 1.98-3.79, P < 0.001), and $150,000/QALY (3.53, 2.37-5.27, P < 0.001) than studies without industry sponsorship. CONCLUSIONS: Our study suggests that there has been a significant sponsorship bias in CEAs in oncology. This bias could have a profound implication on drug pricing and coverage policy making.

Barriers to Accessing Video-Based Telehealth Appointments at a Community Veterinary Clinic During the COVID-19 Pandemic.

Objective: To assess veterinary needs of clients with low socioeconomic status during the COVID-19 pandemic, to explore the impact of the pandemic on marginalized communities, and to understand perceptions regarding barriers and incentives of telehealth appointments as a method to increase care access. Sample: 205 active Community Veterinary Medicine Clinic clients at Tufts at Tech Community Veterinary Clinic in Worcester, MA. Procedures: This cross-sectional study used a survey-based method to assess veterinary needs of clients with low socioeconomic status during the COVID-19 pandemic. The survey measured client perceptions regarding potential barriers and incentives of telehealth appointments. Participants were randomly sampled from a list of active clients and completed the survey either by email or over the phone. The survey was available in both English and Spanish. Clients who completed the questionnaire received credit for a free examination. Results: A total of 205 clients submitted survey responses. Factors affecting access to veterinary care were impacted by the COVID-19 pandemic. Access to reliable internet in the home was reported by 87% (n = 177) of participants. Digital access was correlated with education when controlling for race, income, age, and gender. Education was predictive of comfort with using video-chat (χ2 = 65, df = 24, p ≤ 0.01) and of whether or not clients reported need for assistance for using video-chat (χ2 = 52, df = 18, p ≤ 0.01). Patient education level was significantly predictive of wanting to use telehealth for at least one type of appointment (p ≤ 0.05). Conclusions and Clinical Relevance: The findings indicate that implementing telehealth services at this Community Medicine Clinic is feasible for much of the active clientele and offers a new avenue to provide veterinary care during times of social distancing restrictions and beyond.

Folliculitis Decalvans and Lichen Planopilaris Phenotypic Spectrum: A Case Report.

The folliculitis decalvans (FD) and lichen planopilaris (LPP) phenotypic spectrum combines biphasic features of FD and LPP. It is characterized by successive or concomitant occurrence of pustules, crusts, follicular tufts, perifollicular erythema, perifollicular scales, and cicatricial alopecia and includes mixed histologic features of both FD and LPP. Here, we report the case of a 33-year-old female patient with a 30-year history of FD-LPP phenotypic spectrum lesions.

Unique Behavioral Strategies Adopted by Gravid Ghost Crab Ocypode gaudichaudii to Overcome Dehydration Stress while Minimizing Predation Risks.

Semi-terrestrial crabs require continual access to water to maintain life-sustaining processes such as circulation and feeding. When they emerge from their burrows during low tide to forage, they face the problem of dehydration as they leave the dampness of their burrows. While foraging above ground, water uptake is elicited through capillary action via the hydrophilic setae near the base of the crab's body. Extruded eggs that are borne on the abdominal flap of females tend to obstruct the contact of the setae with the wet sediment. The behavioral adaptations that enable the gravid female painted ghost crab, Ocypode gaudichaudii, to overcome dehydration stress and minimize predation risks at a sandy shore in Playa Venao, Panama were studied using field observations. Comparison of the morphometric measurements of setal tufts between 30 male and 30 female crabs was made to determine if there were morphological adaptations. Analysis of the water uptake behavior from video footage showed that gravid crabs spent a longer duration on water uptake than crabs that did not carry eggs. For the first time, masquerading behavior of a gravid O. gaudichaudii was observed, in which the crab minimized predatory detection by freezing its movement next to a stone enroute to the lower shore during the day. There was no sexual dimorphism in the length and width of the setal tufts between the male and female adult crabs. The results of this study provide the first evidence that the water-uptake behavior in gravid O. gaudichaudii is dependent on behavioral adaptations, as setal tuft morphology does not differ between the sexes.

Structural Abnormalities of the Central Retina in Neurofibromatosis Type 2.

INTRODUCTION: This case-control study seeks to systematically characterize the central retinal findings in a large cohort of patients with neurofibromatosis type 2 (NF2) using spectral domain optical coherence tomography (SD-OCT) as well as the examination of the potential use of this technique as a diagnostic tool in NF2. METHODS: Fifty-four patients with an NF2 diagnosis seen in a quaternary national service were age- and gender-matched to 55 controls from the normal population. Two masked assessors categorized SD-OCT images using predefined abnormalities: retinal tufts, epiretinal membrane (ERM) appearance, retinal hamartoma, and foveal contour. Specificity, sensitivity, and positive and negative predictive values were calculated for each retinal abnormality. Trends of retinal abnormalities with NF2 genetic severity groups (1. tissue mosaic; 2A. mild classic; 2B. moderate classic; and 3. severe) were investigated. RESULTS: We found retinal abnormalities in 26 patients with NF2 (48%) and 2 control patients (4%); retinal tufts were the most common abnormality therein (43%) and were not seen in controls. The specificity and sensitivity of the graded abnormalities on OCT scans in NF2 were 96% and 48%, respectively, with a positive predictive value of 93%. In our cohort, retinal tufts had a specificity of 100%, a sensitivity of 43%, and a positive predictive value of 100%. Retinal hamartomas were seen only in NF2 patients (35% sensitivity and 100% specificity). ERMs had 96% specificity and 13% sensitivity. The proportion of patients with retinal abnormalities increased statistically significantly with NF2 genetic severity; all patients within the 3. severe genetic severity had an abnormal SD-OCT. DISCUSSION/CONCLUSION: We present a systematic study of central retinal abnormalities in an NF2 population as seen on SD-OCT imaging. Our results show a high frequency of retinal abnormalities that are readily detected by SD-OCT imaging. The presence of retinal tufts may be a novel marker of NF2 with both high specificity and a positive predictive value for NF2, compared to other well-known ocular features of NF2, and may have a place in the NF2 diagnostic criteria.

Cobb's Tufts: A Systematic Review.

Cobb's tufts, also known as iris vascular tufts (IVT) and iris microhemangiomas (IMH), are coils of tightly clustered, minute blood vessels at the iris pupillary border. This study aimed to analyze previous literature and provide an update on Cobb's tufts. A systematic literature review was carried out by interrogating PubMed, Google Scholar, Cochrane, and Embase databases. Full-text English language articles of any year were included in this study. A total of 38 articles fulfilled our inclusion criteria. A total of 115 reported cases of Cobb's tufts were incorporated into our review. The age of the patients ranged between 36 and 86 years. No sex or racial predisposition was noted. Most patients had no history of trauma, surgery, or blood dyscrasia. The majority of cases are asymptomatic and bilateral unless a spontaneous hyphema occurs, which most commonly presents as blurred vision. The etiology of this condition remains uncertain; however, a higher incidence has been shown in systemic conditions such as myotonic dystrophy and diabetes. Fluorescein angiography can be utilized to investigate tufts. Management includes treatment of raised intraocular pressure, observation for single bleeds, laser therapy for recurrent hyphemas, and lastly, iridectomy, which is considered in cases of recurrence following laser treatment.

Redescription of Naineris aurantiaca (Müller, 1858) and designation of a neotype from the Brazilian coast (Annelida: Orbiniidae).

The genus Naineris differs from other genera of the Orbiniidae in that all its species possess a rounded prostomium and one or two achaetous rings. Currently, 21 species of this genus have been described worldwide, five of which are recorded from Brazil. Naineris aurantiaca is the only species originally described from the Brazilian coast and the original description is the only record of this species. The description is short and vague, making identification difficult. From recent samples obtained in the type locality of Florianópolis, Brazil, we were able to study specimens of Naineris aurantiaca and redescribe the species. Diagnostic characters for this species are the presence of pre- and post-branchial papillae, anterior branchiae in thoracic segments considerably smaller than those of the rest of the body, distinct dorsal sensory organ from chaetiger 12 onwards, the chaetal arrangement of the thoracic neuropodia (crenulated capillaries in a lower oblique row, uncini in an upper oblique row, subuluncini in two anterior transverse rows, and acicular spines in a posterior row), interramal papillae only present on abdominal parapodia, and the presence of furcate chaetae in the abdominal notopodia. Here, we designate a neotype for the species and discuss the morphological variations we observed among specimens.

Active iris vascular tufts bleeding successfully treated with argon laser photocoagulation.

PURPOSE: Iris vascular tufts (IVT) are rare biomicroscopic capillary outgrowths from the pupillary margins. Patients are usually asymptomatic until presenting with blurred vision due to spontaneous hyphema or with raised intraocular pressure. CASE REPORT: A 61-year-old woman presented to eye casualty with left eye (LE) blurred vision and discomfort for 1 day. Her external ocular examination was unremarkable and visual acuity was 6/6 in the right eye (RE) and 6/9 in the LE. Biomicroscopic examination revealed a 2-mm hyphema in her LE and bilateral multiple small IVT and active bleeding from IVT at the pupillary margin of the LE at the 5 o'clock position. Diagnosis of LE active bleeding from IVT was made and she underwent argon laser photocoagulation directed at the source of bleeding. The bleeding stopped immediately after the second burn. She was followed up for 3 months; her visual acuity was 6/5 and 6/6 in the RE and LE, respectively, with no further problems. CONCLUSIONS: Iris vascular tufts are benign and recurrent hemorrhages are unlikely. Therefore, definitive argon laser photocoagulation or surgical treatment are reserved to arrest further episodes of hyphema. Our case demonstrates the effective use of argon laser photocoagulation to completely arrest active bleeding from IVT and excellent recovery of hyphema with no further problems for 5 years.

Phospho-AXL is widely expressed in glioblastoma and associated with significant shorter overall survival.

Receptor tyrosine kinase AXL (RTK-AXL) is regarded as a suitable target in glioblastoma (GBM) therapy. Since AXL kinase inhibitors are about to get approval for clinical use, patients with a potential benefit from therapy targeting AXL need to be identified. We therefore assessed the expression pattern of Phospho-AXL (P-AXL), the biologically active form of AXL, in 90 patients with newly diagnosed GBM, which was found to be detectable in 67 patients (corresponding to 74%). We identified three main P-AXL expression patterns: i) exclusively in the tumor vasculature (13%), ii) in areas of hypercellularity (35%), or iii) both, in the tumor vasculature and in hypercellular areas of the tumor tissue (52%). Pattern iii) is associated with significant decrease in overall survival (Hazard ratio 2.349, 95% confidence interval 1.069 to 5.162, *p=0.03). Our data suggest that P-AXL may serve as a therapeutic target in the majority of GBM patients.

"Subpial Fan Cell" - A Class of Calretinin Neuron in Layer 1 of Adult Monkey Prefrontal Cortex.

Layer 1 of the cortex contains populations of neurochemically distinct neurons and afferent fibers which markedly affect neural activity in the apical dendritic tufts of pyramidal cells. Understanding the causal mechanisms requires knowledge of the cellular architecture and synaptic organization of layer 1. This study has identified eight morphological classes of calretinin immunopositive (CRet+) neurons (including Cajal-Retzius cells) in layer 1 of the prefrontal cortex (PFC) in adult monkey (Macaca fasicularis), with a distinct class - termed "subpial fan (SPF) cell" - described in detail. SPF cells were rare horizontal unipolar CRet+ cells located directly beneath the pia with a single thick primary dendrite that branched into a characteristic fan-like dendritic tree tangential to the pial surface. Dendrites had spines, filamentous processes and thorny branchlets. SPF cells lay millimeters apart with intralaminar axons that ramified widely in upper layer 1. Such cells were GABA immunonegative (-) and occurred in areas beyond PFC. Interspersed amidst SPF cells displaying normal structural integrity were degenerating CRet+ neurons (including SPF cells) and clumps of lipofuscin-rich cellular debris. The number of degenerating SPF cells increased during adulthood. Ultrastructural analyses indicated SPF cell somata received asymmetric (A - presumed excitatory) and symmetric (S - presumed inhibitory) synaptic contacts. Proximal dendritic shafts received mainly S-type and distal shafts mostly A-type input. All dendritic thorns and most dendritic spines received both synapse types. The tangential areal density of SPF cell axonal varicosities varied radially from parent somata - with dense clusters in more distal zones. All boutons formed A-type contacts with CRet- structures. The main post-synaptic targets were dendritic shafts (67%; mostly spine-bearing) and dendritic spines (24%). SPF-SPF cell innervation was not observed. Morphometry of SPF cells indicated a unique class of CRet+/GABA- neuron in adult monkey PFC - possibly a subtype of persisting Cajal-Retzius cell. The distribution and connectivity of SPF cells suggest they act as integrative hubs in upper layer 1 during postnatal maturation. The main synaptic output of SPF cells likely provides a transminicolumnar excitatory influence across swathes of apical dendritic tufts - thus affecting information processing in discrete patches of layer 1 in adult monkey PFC.

Cross-Sectional Associations between Empirically-Derived Dietary Patterns and Indicators of Disease Risk among University Students.

The transition from adolescence to adulthood is a unique period during which lifelong dietary habits are shaped. Dietary patterns (DPs) among young adults attending college have not been adequately described, and associations between DPs and indicators of disease risk are not well understood in this age group. Dietary data were collected from undergraduates participating in the Tufts Longitudinal Health Study (TLHS; 1998-2007) by Food Frequency Questionnaire (FFQ; n = 1323). DPs were derived using principal components analysis with varimax rotation. Scree plots; eigenvalues; factor loadings; and previous studies were used to determine and label the DPs retained. Cross-sectional relationships between DP scores and anthropometric measures (percent body fat (PBF) and (BMI) and lipid biomarkers (total; HDL and LDL cholesterol; and triglycerides) were assessed with multivariable regression models; adjusted for demographics; physical activity; smoking; intention to gain/lose weight; and total energy intake. Effect modification by sex was tested. Three DPs were identified: Prudent; Western; and Alcohol. Greater adherence to the Prudent DP was associated with favorable anthropometric outcomes. The Alcohol DP was associated with a favorable lipid profile. Associations between the Western DP and blood lipids differed by sex; with unfavorable impact observed only among males. Our findings add to the literature linking DPs in young adults with measurable adiposity and cardiometabolic outcomes; suggesting that improving nutrition among college students could reduce chronic disease risk.

Tarantulas (Araneae: Theraphosidae) use different adhesive pads complementarily during climbing on smooth surfaces: experimental approach in eight arboreal and burrower species.

Tarantulas are large spiders with adhesive setae on their legs, which enable them to climb on smooth vertical surfaces. The mechanism proposed to explain adhesion in tarantulas is anisotropic friction, where friction is higher when the leg pushes than when it pulls. However, previous studies and measurements of adhesion in theraphosids were performed using dead specimens. To test their ability to climb, we studied static friction of live theraphosid spiders on different surfaces and at different inclines. We compared burrower with arboreal species to test the hypothesis of higher friction in arboreal tarantulas. We found a complementary participation of claw tufts and scopula of anterior and posterior legs when the tarantula climbs. The mechanics of climbing in association with the biological characteristics of the species are discussed.

The politics of Golden Rice.

Genetic knowledge applicable to crop improvement has erupted over the past 60 years, and the techniques of introducing genes from one organism to another have enabled new varieties of crops not achievable by previously available methodologies of crop breeding. Research and particularly development of these GMO-crops to a point where they are useful for growers and consumers in most countries is subject to complex national and international rules arising out of the UN's Cartagena Protocol on Biosafety to the Convention on Biological Diversity, with 167 country signatories. (The USA and Canada are not signatories.) The Protocol was developed based on concerns initially expressed in the 1970's that such technology presented unusual risks to man and the environment. Those ideas have comprehensively and authoritatively been proven to be wrong. The Protocol has nevertheless spawned significant regulatory obstacles to the development of GMO-crop technology at great cost to global society and in conflict with many other UN objectives. The suspicion induced by the Protocol is also widely used, overtly or covertly, for political purposes. These points are illustrated by reference to the not-for-profit Golden Rice project.

Intratumoral peripheral small papillary tufts: a diagnostic clue of renal tumors associated with Birt-Hogg-Dubé syndrome.

In this article, we searched for the common histologic characteristic of renal tumors in patients with Birt-Hogg-Dubé syndrome (BHDS). We selected 6 patients with histologically confirmed renal tumor in BHDS. Germline FLCN gene mutation has been identified in 5 patients. Multifocality and bilaterality of the renal tumors were pathologically or radiologically confirmed in 5 and 2 cases, respectively. Histologic subtypes of the dominant tumor included 3 previously described hybrid oncocytic tumors, one composite chromophobe/papillary/clear cell renal cell carcinoma (RCC) and one unclassified RCC resembling hybrid chromophobe/clear cell RCC. In one case, chromophobe RCC and clear cell RCC were separately observed. Small papillary lesions located in the peripheral area of the tumor, which we designated as intratumoral peripheral small papillary tufts, were identified in all patients. In conclusion, multifocality/bilaterality of renal tumors, discordance of histologic subtypes, and the presence of intratumoral peripheral small papillary tufts may be important clues to identify BHDS-associated renal tumors.

A comparative study on component volumes from outer to inner dental enamel in relation to enamel tufts.

BACKGROUND AND AIM: Dental enamel presents marked mechanical properties gradients from outer to inner enamel, a region lacking component volumes profiles. Tufts, structures of inner enamel, have been shown to play a role in enamel resilience. We aimed at comparing component volumes from inner to outer enamel in relation to enamel tufts. MATERIALS AND METHODS: Transversal ground sections from the cervical half of unerupted human third molars (n=10) were prepared and histological points were selected along transversal lines (extending from innermost to outer enamel) traced across tufts and adjacent control areas without tufts. Component volumes were measured at each histological point. RESULTS: Component volumes ranges were: 70.6-98.5% (mineral), 0.02-20.78% (organic), 3.8-9.8% (total water), 3-9% (firmly bound water), and 0.02-3.3% (loosely bound water). Inner enamel presented the lowest mineral volumes and the highest non-mineral volumes. Mineral, water and organic contents differed as a function of the distance from innermost enamel but not between the tuft and control lines. Tufts presented opaqueness in polarizing microscopy (feature of fracture lines). Organic volume gradient correlated with a relatively flat profile of loosely bound water. Inner, but not outer enamel, rehydrated after air-dried enamel was heated to 50°C and re-exposed to room conditions, as predicted by the organic/water gradient profiles. CONCLUSIONS: Component volumes vary markedly from outer to inner enamel, but not between areas with or without tufts (that behave like fracture lines under polarizing microscopy).

[Iris microhaemangiomas: presentation of a case]. / Microhemangiomas iridianos: a propósito de un caso.

CASE REPORT: A 74 year-old woman present with blurry vision of 12 hour duration in her right eye, and with no other symptoms. Biomicroscopic examination revealed a 3 mm hyphaema in her right eye and multiple nodular structures in the pupillary margin of both eyes. DISCUSSION: Iris tufts are vascular anomalies unrelated to ischaemia that must be included in the differential diagnosis of spontaneous hyphaema.

Catalogue of tooth brush head designs.

PURPOSE: Manual toothbrushes (MTBs) and power toothbrushes (PTBs) are effective oral physiotherapy aids for plaque removal. End-rounded bristles are safer and reduce damage to oral tissues. Nylon bristles are more effective in plaque removal because the bristle is stiffer than natural bristles. In the last 10 years the number of options for MTBs and PTBs has expanded significantly and there is very little information providing a reference frame for the design characteristics of the heads. The present in vitro study characterized a variety of MTB and PTB heads to provide a reference library for other research comparisons which might be made. METHODS: Various commercial MTB and PTB heads were used to characterize the following: bristle size, shape, diameter, number of tufts, number of bristles per tuft and surface characteristics. Photographs were collected from the side, at 45 degrees and the top of each toothbrush (TB) head using a scanning electron microscope and digital camera. Images were analyzed (Soft Imaging System) for bristle features and designs. One-way ANOVA (p ≤ 0.05) was performed to detect differences among TB types within MTB and PTB groups and between pooled values for MTB and PTB groups. RESULTS: There were significant differences (p ≤ 0.05) in toothbrush bristle diameter and bristle shape. In contrast, there were no significant differences between PTB vs. MTB in regards to bristle diameter, bristle count and tuft count. CONCLUSION: The results suggest that although there are wide variations in toothbrush head designs, significant differences were found only in relation to bristle diameter and shape.