Superior Capsule Reconstruction Is a Viable Option for Patients with Symptomatic, Isolated, and Irreparable Supraspinatus Tears.

PURPOSE: To evaluate the outcome of superior capsular reconstruction for isolated subscapularis tears using a decellularized porcine allograft as a superior capsular reconstruction. METHODS: Patients who had symptomatic tears of supraspinatus who had failed to improve a conservative rehabilitation program were included. Previous surgery to the shoulder was not a bar to inclusion. Patients were assessed preoperatively and postoperatively with the Oxford Shoulder Score (OSS), the single assessment numeric evaluation (SANE) score, as well as clinically assessed for their shoulder range of motion (ROM). Patients were followed up with in-person clinic appointments for the first year, followed by a postal questionnaire and telephone consultation at a minimum of 2 years following surgery. RESULTS: Twenty patients (11 males and 9 females) with a mean age of 67.5 years were included (range: 54-72 years). The average follow-up period was 31 months (24-50). The mean improvement in OSS was 14 points (P < .001), SANE score was 27 points (P < .01). Significant improvements in mean ROM were recorded (flexion 80.7°; P < .001; abduction: 81°; P < .001; external rotation: 31°; P < .001). Six patients suffered SCR failures diagnosed by magnetic resonance imaging, despite this they still recorded improvements in recorded OSS, SANE and ROM (excluding external rotation). Patient demographics for failed superior capsule reconstruction (SCR) highlighted smoking and revision surgery as risk factors. CONCLUSIONS: SCR appears to be a viable option for patients with symptomatic, isolated, and irreparable tears of the supraspinatus. Our results demonstrate that there are significant improvements in outcome scores and active range of motion, even in the subgroup in whom postoperative structural failure of the SCR was identified. We recommend caution in patients who have previously failed rotator cuff repair and in heavy smokers. LEVEL OF EVIDENCE: Level IV, therapeutic case series

Amyloid-beta induced CA1 pyramidal cell loss in young adult rats is alleviated by systemic treatment with FGL, a neural cell adhesion molecule-derived mimeticPeptide

Increased levels of neurotoxic amyloid-beta in the brain are a prominent feature of Alzheimer’s disease. FG-Loop (FGL), a neural cell adhesion molecule-derived peptide that corresponds to its second fibronectin type III module, has been shown to provide neuroprotection against a range of cellular insults. In the present study impairments in social recognition memory were seen 24 days after a 5 mg/15 µl amyloid-beta(25–35) injection into the right lateral ventricle of the young adult rat brain. This impairment was prevented if the animal was given a systemic treatment of FGL. Unbiased stereology was used to investigate the ability of FGL to alleviate the deleterious effects on CA1 pyramidal cells of the amyloid-beta(25–35) injection. NeuN, a neuronal marker (for nuclear staining) was used to identify pyramidal cells, and immunocytochemistry was also used to identify inactive glycogen synthase kinase 3beta (GSK3β) and to determine the effects of amyloid-beta(25–35) and FGL on the activation state of GSK3β, since active GSK3β has been shown to cause a range of AD pathologies. The cognitive deficits were not due to hippocampal atrophy as volume estimations of the entire hippocampus and its regions showed no significant loss, but amyloid-beta caused a 40% loss of pyramidal cells in the dorsal CA1 which was alleviated partially by FGL. However, FGL treatment without amyloid-beta was also found to cause a 40% decrease in CA1 pyramidal cells. The action of FGL may be due to inactivation of GSK3β, as an increased proportion of CA1 pyramidal neurons contained inactive GSK3β after FGL treatment. These data suggest that FGL, although potentially disruptive in nonpathological conditions, can be neuroprotective in disease-like conditions

Transparent predictive modelling of the twin screw granulation process using a compensated interval type-2 fuzzy system

In this research, a new systematic modelling framework which uses machine learning for describing the granulation process is presented. First, an interval type-2 fuzzy model is elicited in order to predict the properties of the granules produced by twin screw granulation (TSG) in the pharmaceutical industry. Second, a Gaussian mixture model (GMM) is integrated in the framework in order to characterize the error residuals emanating from the fuzzy model. This is done to refine the model by taking into account uncertainties and/or any other unmodelled behaviour, stochastic or otherwise. All proposed modelling algorithms were validated via a series of Laboratory-scale experiments. The size of the granules produced by TSG was successfully predicted, where most of the predictions fit within a 95% confidence interval

Characteristics of Multi-Component Formulation Granules Formed using Distributive Mixing Elements in Twin Screw Granulation

This work examines the influence of pharmaceutical powder formulation characteristics on granule properties formed using distributive mixing elements (DMEs) in twin screw granulation. High and low drug dose formulations with three different active pharmaceutical ingredients (APIs) were considered. The type and concentration of the API in the formulation significantly affected the dry blend particle size distribution and the wet blend dynamic yield strength. However, despite the differences in blend properties, the granule size distributions were not significantly affected by the type of API used. The granule size distributions were solely functions of the liquid-to-solid ratio and the screw element geometry. However, the granule porosities were observed to be dependent on both the liquid-to-solid ratio and the dynamic yield strength of the blends. This work is the first to study the influence of drug loading and API type on the granule attributes produced using distributive mixing elements

Electrophysiological Heterogeneity of Fast-Spiking Interneurons: Chandelier versus Basket Cells

In the prefrontal cortex, parvalbumin-positive inhibitory neurons play a prominent role in the neural circuitry that subserves working memory, and alterations in these neurons contribute to the pathophysiology of schizophrenia. Two morphologically distinct classes of parvalbumin neurons that target the perisomatic region of pyramidal neurons, chandelier cells (ChCs) and basket cells (BCs), are generally thought to have the same "fast-spiking" phenotype, which is characterized by a short action potential and high frequency firing without adaptation. However, findings from studies in different species suggest that certain electrophysiological membrane properties might differ between these two cell classes. In this study, we assessed the physiological heterogeneity of fast-spiking interneurons as a function of two factors: species (macaque monkey vs. rat) and morphology (chandelier vs. basket). We showed previously that electrophysiological membrane properties of BCs differ between these two species. Here, for the first time, we report differences in ChCs membrane properties between monkey and rat. We also found that a number of membrane properties differentiate ChCs from BCs. Some of these differences were species-independent (e.g., fast and medium afterhyperpolarization, firing frequency, and depolarizing sag), whereas the differences in the first spike latency between ChCs and BCs were species-specific. Our findings indicate that different combinations of electrophysiological membrane properties distinguish ChCs from BCs in rodents and primates. Such electrophysiological differences between ChCs and BCs likely contribute to their distinctive roles in cortical circuitry in each species. © 2013 Povysheva et al

When a 520 million-year-old Chengjiang fossil meets a modern micro-CT - a case study

The 520 million-year-old Chengjiang biota of China (UNESCO World Heritage) presents the earliest known evidence of the so-called Cambrian Explosion. Studies, however, have mainly been limited to the information exposed on the surface of the slabs. Thus far, structures preserved inside the slabs were accessed by careful removal of the matrix, in many cases with the unfortunate sacrifice of some "less important" structures, which destroys elements of exceptionally preserved specimens. Here, we show for the first time that microtomography (micro-CT) can reveal structures situated inside a Chengjiang fossil slab without causing any damage. In the present study a trilobitomorph arthropod (Xandarella spectaculum) can be reliably identified only with the application of micro-CT. We propose that this technique is an important tool for studying three-dimensionally preserved Chengjiang fossils and, most likely, also those from other biota with a comparable type of preservation, specifically similar iron concentrations

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn^(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn^(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn^(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here

Origins of Cortical GABAergic Neurons in the Cynomolgus Monkey

In human most cortical γ-aminobutyric acidergic (GABAergic) neurons are produced in the proliferative zones of the dorsal telencephalon in contrast to rodents. We report that in cynomolgus monkey fetuses cortical GABAergic neurons are generated in the proliferative zones of the dorsal telencephalon, in addition to the proliferative region of the ventral telencephalon, the ganglionic eminence (GE), however, with a temporal delay. GABAergic neuron progenitors labeled for Mash1 and GAD65 were present mainly in the GE at embryonic days (E) 47–55, and in the entire dorsal telencephalon at E64–75. These progenitors within the dorsal telencephalon are generated locally rather than in the GE. The ventral and dorsal lineages of cortical GABAergic neurons display different laminar distribution. Early generated GABAergic neurons from the GE mostly populate the marginal zone and subplate, whereas cortical plate GABAergic neurons originate from both ventral and dorsal telencephalon. A differential regulation of the two GABA synthesizing enzymes (GAD65 and GAD67) parallels GABAergic neuron differentiation. GAD65 is preferentially expressed in GABAergic progenitors and migrating neurons, GAD67 in morphologically differentiated neurons. Therefore, the dorsal telencephalic origin of cortical GABAergic neurons is not human-specific but appears as a former event in the ascent of evolution that could provide GABAergic neurons to an expending neocortex

Prelimbic and Infralimbic Prefrontal Cortex Interact during Fast Network Oscillations

Background: The medial prefrontal cortex has been implicated in a variety of cognitive and executive processes such as decision making and working memory. The medial prefrontal cortex of rodents consists of several areas including the prelimbic and infralimbic cortex that are thought to be involved in different aspects of cognitive performance. Despite the distinct roles in cognitive behavior that have been attributed to prelimbic and infralimbic cortex, little is known about neuronal network functioning of these areas, and whether these networks show any interaction during fast network oscillations. Methodology/Principal Findings: Here we show that fast network oscillations in rat infralimbic cortex slices occur at higher frequencies and with higher power than oscillations in prelimbic cortex. The difference in oscillation frequency disappeared when prelimbic and infralimbic cortex were disconnected. Conclusions/Significance: Our data indicate that neuronal networks of prelimbic and infralimbic cortex can sustain fast network oscillations independent of each other, but suggest that neuronal networks of prelimbic and infralimbic cortex ar