Bioelectronic DNA detection of human papillomaviruses using eSensor™: a model system for detection of multiple pathogens

BACKGROUND: We used human papillomaviruses (HPV) as a model system to evaluate the utility of a nucleic acid, hybridization-based bioelectronic DNA detection platform (eSensor™) in identifying multiple pathogens. METHODS: Two chips were spotted with capture probes consisting of DNA oligonucleotide sequences specific for HPV types. Electrically conductive signal probes were synthesized to be complementary to a distinct region of the amplified HPV target DNA. A portion of the HPV L1 region that was amplified by using consensus primers served as target DNA. The amplified target was mixed with a cocktail of signal probes and added to a cartridge containing a DNA chip to allow for hybridization with complementary capture probes. RESULTS: Two bioelectric chips were designed and successfully detected 86% of the HPV types contained in clinical samples. CONCLUSIONS: This model system demonstrates the potential of the eSensor platform for rapid and integrated detection of multiple pathogens

Nutritional Quality of Leaves and Unripe Fruit Consumed as Famine Foods by the Flying Foxes of Samoa

Many tropical herbivores alter their diets throughout the year in response to different levels of food availability. Fruit bats, including Pteropus samoensis Peale and Pteropus tonganus Quoy & Gaimard, are phytophagous species that may increase their consumption of foods such as unripe fruit and leaves in periods of low fruit diversity and volume. These periods include the tropical dry season or following the frequent hurricanes that batter the Samoan Archipelago. We examined the nutritional composition of leaves and immature fruits and compared the levels of organic and mineral nutrients with those of ripe fruit. We used principal components analysis (PCA) to examine patterns of variation in nutrient components of leaves, unripe fruit, and ripe fruit, as well as to compare the mean levels of nutrients. Overall, unripe fruit provided levels of nutrients comparable with those of ripe fruit of the same species for many organic and mineral components. Unripe fruit were only half as rich in iron as ripe fruit, but unripe fruit had high levels of calcium compared with ripe fruit of the same species. Leaves are often cited as a rich source of protein for fruit bats, and our results were consistent with this suggestion. Leaves were also found to be rich in zinc, manganese, and calcium. Therefore, flying foxes and other herbivores probably do not avoid unripe fruits and leaves because of their low nutrient levels. It may be that these famine foods are not normally consumed because of the presence of secondary compounds, low concentrations of palatable sugars, or a distasteful and hard pericarp on unripe fruits

High-Grade Partial and Retracted (less than 2 cm) Proximal Hamstring Ruptures: Nonsurgical Treatment Revisited

BACKGROUND: High-grade partial proximal hamstring tears and complete tears with retraction less than 2 cm are a subset of proximal hamstring injuries where, historically, treatment has been nonoperative. It is unknown how nonoperative treatment compares with operative treatment. HYPOTHESIS: The clinical and functional outcomes of nonoperative and operative treatment of partial/complete proximal hamstring tears were compared. We hypothesize that operative treatment of these tears leads to better clinical and functional results. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective review identified patients with a high-grade partial or complete proximal hamstring rupture with retraction less than 2 cm treated either operatively or nonoperatively from 2007 to 2015. All patients had an initial period of nonoperative treatment. Surgery was offered if patients had continued pain and/or limited function refractory to nonoperative treatment with physical therapy. Outcome measures were each patient\u27s strength perception, ability to return to activity, Lower Extremity Functional Scale (LEFS) score, Short Form-12 (SF-12) physical and mental component outcome scores, distance traversed by a single-leg hop, and Biodex hamstring strength testing. RESULTS: A total of 25 patients were enrolled in the study. The 15 patients who were treated nonoperatively sustained injuries at a mean age of 55.73 +/- 14.83 years and were evaluated 35.47 +/- 30.35 months after injury. The 10 patients who elected to have surgery sustained injuries at 50.40 +/- 6.31 years of age (P = .23) and were evaluated 30.11 +/- 19.43 months after surgery. LEFS scores were significantly greater for the operative group compared with the nonoperative group (77/80 vs 64.3/80; P = .01). SF-12 physical component scores for the operative group were also significantly greater (P = .03). Objectively, operative and nonoperative treatment modalities showed no significant difference in terms of single-leg hop distance compared with each patient\u27s noninjured leg (P = .26) and torque deficit at isokinetic speeds of 60 and 180 deg/s (P = .46 and .70, respectively). CONCLUSION: Patients who undergo operative and nonoperative treatment of high-grade partial and/or complete proximal hamstring tears with \u3c 2 cm retraction demonstrate good clinical and functional outcomes. In our series, 40% of patients treated nonoperatively with physical therapy went on to have surgery. For those patients with persistent pain and/or loss of function despite conservative treatment, surgical repair is a viable treatment option that is met with good results

Efficacy of melatonin in term neonatal models of perinatal hypoxia‐ischaemia

OBJECTIVE: Neonatal encephalopathy (NE) is an important cause of mortality and disability worldwide. Therapeutic hypothermia (HT) is an effective therapy, however not all babies benefit. Novel agents are urgently needed to improve outcomes. Melatonin in preclinical studies has promising neuroprotective properties. This meta-analysis assessed the efficacy of melatonin in term animal models of NE on cerebral infarct size, neurobehavioural tests and cell death. METHODS: A literature search was carried out using Embase, MEDLINE and Web of Science (31 May 2021). We identified 14 studies and performed a meta-analysis with a random effects model using standardised mean difference (SMD) as the effect size. The risk of bias was assessed using the Systematic Review Centre for Laboratory animal Experimentation tool and publication bias was assessed with funnel plots, and adjusted using trim and fill analysis. Subgroup and meta-regression analyses were performed to assess the effects of study design variables. RESULTS: We observed significant reduction in brain infarct size (SMD -2.05, 95% CI [-2.93, -1.16]), improved neurobehavioural outcomes (SMD -0.86, 95% CI [-1.23, -0.53]) and reduction in cell death (SMD -0.60, 95% CI [-1.06, -0.14]) favouring treatment with melatonin. Neuroprotection was evident as a single therapy and combined with HT. Subgroup analysis showed greater efficacy with melatonin given before or immediately after injury and with ethanol excipients. The overall effect size remained robust even after adjustment for publication bias. INTERPRETATION: These studies demonstrate a significant neuroprotective efficacy of melatonin in term neonatal models of hypoxia-ischaemia, and suggest melatonin is a strong candidate for translation to clinical trials in babies with moderate-severe NE

Efficacy of melatonin in term neonatal models of perinatal hypoxia-ischaemia

OBJECTIVE: Neonatal encephalopathy (NE) is an important cause of mortality and disability worldwide. Therapeutic hypothermia (HT) is an effective therapy, however not all babies benefit. Novel agents are urgently needed to improve outcomes. Melatonin in preclinical studies has promising neuroprotective properties. This meta-analysis assessed the efficacy of melatonin in term animal models of NE on cerebral infarct size, neurobehavioural tests and cell death. METHODS: A literature search was carried out using Embase, MEDLINE and Web of Science (31 May 2021). We identified 14 studies and performed a meta-analysis with a random effects model using standardised mean difference (SMD) as the effect size. The risk of bias was assessed using the Systematic Review Centre for Laboratory animal Experimentation tool and publication bias was assessed with funnel plots, and adjusted using trim and fill analysis. Subgroup and meta-regression analyses were performed to assess the effects of study design variables. RESULTS: We observed significant reduction in brain infarct size (SMD -2.05, 95% CI [-2.93, -1.16]), improved neurobehavioural outcomes (SMD -0.86, 95% CI [-1.23, -0.53]) and reduction in cell death (SMD -0.60, 95% CI [-1.06, -0.14]) favouring treatment with melatonin. Neuroprotection was evident as a single therapy and combined with HT. Subgroup analysis showed greater efficacy with melatonin given before or immediately after injury and with ethanol excipients. The overall effect size remained robust even after adjustment for publication bias. INTERPRETATION: These studies demonstrate a significant neuroprotective efficacy of melatonin in term neonatal models of hypoxia-ischaemia, and suggest melatonin is a strong candidate for translation to clinical trials in babies with moderate-severe NE

Tau PET and multimodal brain imaging in patients at risk for chronic traumatic encephalopathy.

ObjectiveTo characterize individual and group-level neuroimaging findings in patients at risk for Chronic Traumatic Encephalopathy (CTE).MethodsEleven male patients meeting criteria for Traumatic Encephalopathy Syndrome (TES, median age: 64) underwent neurologic evaluation, 3-Tesla MRI, and PET with [18F]-Flortaucipir (FTP, tau-PET) and [11C]-Pittsburgh compound B (PIB, amyloid-PET). Six patients underwent [18F]-Fluorodeoxyglucose-PET (FDG, glucose metabolism). We assessed imaging findings at the individual patient level, and in group-level comparisons with modality-specific groups of cognitively normal older adults (CN). Tau-PET findings in patients with TES were also compared to a matched group of patients with mild cognitive impairment or dementia due to Alzheimer's disease (AD).ResultsAll patients with TES sustained repetitive head injury participating in impact sports, ten in American football. Three patients met criteria for dementia and eight had mild cognitive impairment. Two patients were amyloid-PET positive and harbored the most severe MRI atrophy, FDG hypometabolism, and FTP-tau PET binding. Among the nine amyloid-negative patients, tau-PET showed either mildly elevated frontotemporal binding, a "dot-like" pattern, or no elevated binding. Medial temporal FTP was mildly elevated in a subset of amyloid-negative patients, but values were considerably lower than in AD. Voxelwise analyses revealed a convergence of imaging abnormalities (higher FTP binding, lower FDG, lower gray matter volumes) in frontotemporal areas in TES compared to controls.ConclusionsMildly elevated tau-PET binding was observed in a subset of amyloid-negative patients at risk for CTE, in a distribution consistent with CTE pathology stages III-IV. FTP-PET may be useful as a biomarker of tau pathology in CTE but is unlikely to be sensitive to early disease stages

The Beneficial Effects of Melatonin Administration Following Hypoxia-Ischemia in Preterm Fetal Sheep

Melatonin (MLT) is an endogenous hormone that controls circadian cycle. MLT has additional important properties that make it appealing as a neuroprotective agent—it is a potent anti-oxidant, with anti-apoptotic and anti-inflammatory properties. MLT is safe for administration during pregnancy or to the newborn after birth, and can reduce white matter brain injury under conditions of chronic fetal hypoxia. Accordingly, in the current study, we examined whether an intermediate dose of MLT could restore white matter brain development when administered after an acute hypoxic ischemic (HI) insult in preterm fetal sheep. Fifteen fetal sheep at 95–98 days gestation were instrumented with femoral artery and vein catheters, and a silastic cuff placed around the umbilical cord. At 102 days gestation, the cuff was inflated, causing complete umbilical cord occlusion for 25 min in 10 fetuses, to induce acute severe HI. Five HI fetuses received intravenous MLT for 24 h beginning at 2 h after HI. The remaining five fetuses were administered saline alone. Ten days after HI, the fetal brain was collected from each animal and white and gray matter neuropathology assessed. HI caused a significant increase in apoptotic cell death (TUNEL+), activated microglia (Iba-1+), and oxidative stress (8-OHdG+) within the subventricular and subcortical white matter. HI reduced the total number of oligodendrocytes and CNPase+ myelin density. MLT administration following HI decreased apoptosis, inflammation and oxidative stress within the white matter. MLT had intermediate benefits for the developing white matter: it increased oligodendrocyte cell number within the periventricular white matter only, and improved CNPase+ myelin density within the subcortical but not the striatal white matter. MLT administration following HI was also associated with improved neuronal survival within the cortex. Neuropathology in preterm infants is complex and mediated by multiple mechanisms, including inflammation, oxidative stress and apoptotic pathways. Treatment with MLT presents a safe approach to neuroprotective therapy in preterm infants but appears to have brain region-specific benefits within the white matter

What sets lower limits to phytoplankton stocks in high-nitrate, low-chlorophyll regions of the open ocean?

Phytoplankton biomass in high-nitrate, low-chlorophyll (HNLC) ocean regions exhibits a pronounced stability: variation occurs only within a narrow range of values. The magnitude of this variation has profound ecological and geochemical consequences. While mechanisms believed to set the upper limits to HNLC phytoplankton biomass (iron limitation, microherbivore grazing) have received much recent attention, mechanisms setting the lower limits are largely unknown. The demonstrated importance of planktonic micrograzers, largely protists, in removing phytoplankton biomass in HNLC regions suggests that micrograzer behavioral and physiological capabilities may hold the key. This will be the case at any level of phytoplankton cell division greater than zero, regardless of the extent of growth rate limitation by resource (e.g. iron, light) availability. Indeed, HNLC plankton dynamics models almost universally include several biological responses that set lower phytoplankton biomass limits and confer temporal stability, including substantial feeding thresholds, zero micrograzer metabolic costs, and no micrograzer mortality at low food levels. Laboratory observations of these same biological responses in protist grazers are equivocal. There are no direct observations of substantive feeding thresholds, and many heterotrophic protists exhibit significant rates of respiration and mortality (cell lysis) at very low food levels. We present several candidate explanations for the discrepancy between laboratory observations and model biological 'requirements'. Firstly, laboratory-derived rate measurements may be biased by use of species and prey concentrations that are not representative of HNLC communities. Secondly, model micrograzer features may be a proxy for other stabilizing phenomena such as spatial heterogeneity ('patchiness') or carnivory (top-down control of rnicroherbivores), though a logical analysis indicates that neither is likely to provide robust stabilization of lower phytoplankton biomass limits. Lastly, the highly plastic feeding capabilities of protist grazers, which include switching between phytoplankton and alternative prey such as bacteria, detritus, and other microherbivores, are a probable locus for stabilization of biomass limits. The extent to which such behavioral plasticity functions on the level of individuals or of species assemblages is unknown. We advocate a coupled modeling and experimental approach to further progress in understanding this key feature of HNLC ecosystems.Keywords: Planktonic food webs, Phytoplankton, Microzooplankton, Plankton dynamics models, Feeding behavior, Grazer