Cisgenics and intragenics: boon or bane for crop improvement.

Recent advances in molecular biology and genetic engineering have made it possible to increase agricultural yields when compared to conventional methods. However, lots of challenges are to be addressed due to changing climatic conditions. Although genetically modified organisms (GMOs) have proven their potential in a few crops, but needs to be explored in majority of the field/vegetable crops to overcome food and nutritional security in view of alarming population explosion. In spite of advantages from GMO crops due to the presence of foreign DNA, queries regarding their safety, environmental dangers and health effects needs to be addressed. One of the major environmental issues concerning transgenic crops is the mixing of genetic components across species that cannot hybridize naturally. Due to these limitations, new revolutionary technologies have been developed, such as intragenesis and cisgenesis for the transformation and development of superior plants. While cisgenesis entails genetic modification employing a complete copy of natural genes with their native regulatory components that only belong to sexually compatible species, intragenesis refers to the transfer of unique combinations of genes and regulatory sequence inside the same species. In cisgenesis, the donor genes are the same genes employed in conventional breeding. The two benefits of cisgenics are avoiding linkage drag and making greater use of existing gene alleles. This method significantly shortens the time it takes to breed plants by combining conventional methods with cutting-edge biotechnological tools. Because of this, plant genomes can be altered without causing drastic changes to the whole plant population and the environmental effects of cisgenic plants cannot be compared to those of transgenics. Transgenesis and cisgenesis share the same transformation methods; hence, cisgenic, intragenic and transgenic plants produced through random insertion do not pose any distinct risks with regard to host genome modifications. In contrast, using new genome techniques lessens the dangers related to potential unintentional changes to the host DNA. The use of cisgenesis and intragenesis as alternatives to transgenesis has been restricted to a small number of species due to incomplete understanding of the required regulatory sequences.

Biomedical instrumentation of photoacoustic imaging and quantitative sensing for clinical applications.

Photoacoustic (PA) imaging has been well researched over the last couple of decades and has found many applications in biomedical engineering. This has evinced interest among many scientists in developing this as a compact instrument for biomedical diagnosis. This review discusses various instrumentation developments for PA experimental setups and their applications in the biomedical diagnostic field. It also covers the PA spectral response or PA sensing technique, which uses the spectral information of the PA signal and performs sensing to deliver a fast, cost-effective, and compact screening tool instead of imaging. Primarily, this review provides an overview of PA imaging concepts and the development of hardware instrumentation systems in both the excitation and acquisition stages of this technique. Later, the paper discusses PA sensing, the quantitative spectral parameter extraction from the PA spectrum, and the correlation study of the spectral parameters with the physical parameters of the tissue. This PA sensing technique was used to diagnose various diseases, such as thyroid nodules, breast cancer, renal disorders, and zoonotic diseases, based on the mechanical and biological characteristics of the tissues. The paper culminates with a discussion section that provides future developments that are necessary to take this technique into clinical applications as a quantitative PA imaging technique.

Evaluation of modified RENAL nephrometry score in the prediction of perioperative outcomes of open partial nephrectomy.

Introduction: RENAL nephrometry score (RNS) is a standardized system to grade the complexity of renal masses, but it does not correlate well with the perioperative outcomes of open partial nephrectomy (OPN). To overcome these shortcomings, a modified RNS (MRNS) has been proposed. In this study, we evaluated the MRNS and its role in predicting the perioperative outcomes of OPN. Methods: This was a prospective observational study performed at a tertiary care hospital to evaluate the efficacy of MRNS in predicting the perioperative outcomes of OPN. Sixty-four cases were included in the study. Demographic parameters, tumor characteristics, and perioperative outcomes were analyzed. Correlation with the post-operative outcomes and the strengths of MRNS were compared with various other nephrometry scores. Results: The mean age of the patients was 52.89 years, 60.9% were male and 53.1% had a right-sided mass. The comorbidities, body mass index, and performance scores were evenly distributed across the complexity groups (P > 0.05). The mean tumor size was 4.13 cm and the mean MRNS and RNS were 9.45 and 6.1, respectively. 60.9% of the cases had no complications. Major complications (Clavien-Dindo grade [CDG] 3+) were noted in five cases (7.8%). The trifecta of neargin, ischemia, and complications (MICs) score was achieved in 85.9% and was achieved in 71.9% of the cases. MRNS was found to be an independent predictor of the trifecta outcomes (P = 0.04). Receiver-operating characteristic curve of MRNS analyzing the major complications as per the CDG showed an area under the curve of. 804, indicating good prediction of complications by the MRNS. Conclusions: MRNS improves the predicting power of RNS by attributing enhanced scores to key elements and by adding new elements. Also, MRNS has good ability to predict the achievement of the trifecta and MIC.

Infection with Decapod iridescent virus 1: an emerging disease in shrimp culture.

For the last 3 decades the shrimp industries has been plagued by many destructive diseases, which have resulted in severe production and economic losses to many aquaculture countries. These include viral, bacterial and parasitic diseases. Recently, another emerging viral disease is threatening the shrimp culture industry in Asia. The virus originally called Cherax quadricarinatus iridovirus (CQIV) or Shrimp hemocyte iridescent virus (SHIV) and now classified within the proposed genus Decapodiridovirus and formally named as Decapod iridescent virus 1 (DIV1) by International Committee on Taxonomy of Viruses (ICTV). The virus was first detected as early as 2014 from Cherax quadricarinatus samples in Fujian Province and farmed white leg shrimp Penaeus vannamei samples from Zhejiang Province. This review article encompasses the significance of the DIV1 and their implications for the future of the global aquaculture.

Safety of emergency, elective and day case operating during the winter period at East Suffolk and North Essex NHS Foundation Trust: lessons from the outcomes of 4,254 surgical patients from the first COVID-19 wave.

BACKGROUND: There is limited evidence on perioperative outcomes of surgical patients during the COVID-19 pandemic to inform continued operating into the winter period. METHODS: We retrospectively analysed the rate of 30-day COVID-19 transmission and mortality of all surgical patients in the three hospitals in our trust in the East of England during the first lockdown in March 2020. All patients who underwent a swab were swabbed on or 24 hours prior to admission. RESULTS: There were 4,254 patients and an overall 30-day mortality of 0.99%. The excess surgical mortality in our region was 0.29%. There were 39 patients who were COVID-19 positive within 30 days of admission, 12 of whom died. All 12 were emergency admissions with a length of stay longer than 24 hours. There were three deaths among those who underwent day case surgery, one of whom was COVID-19 negative, and the other two were not swabbed but not suspected to have COVID-19. There were two COVID-19 positive elective cases and none in day case elective or emergency surgery. There were no COVID-19 positive deaths in elective or day case surgery. CONCLUSIONS: There was a low rate of COVID-19 transmission and mortality in elective and day case operations. Our data have allowed us to guide patients in the consent process and provided the evidence base to restart elective and day case operating with precautions and regular review. A number of regions will be similarly affected and should perform a review of their data for the winter period and beyond.

Overcoming resistance to BRAFV600E inhibition in melanoma by deciphering and targeting personalized protein network alterations.

BRAFV600E melanoma patients, despite initially responding to the clinically prescribed anti-BRAFV600E therapy, often relapse, and their tumors develop drug resistance. While it is widely accepted that these tumors are originally driven by the BRAFV600E mutation, they often eventually diverge and become supported by various signaling networks. Therefore, patient-specific altered signaling signatures should be deciphered and treated individually. In this study, we design individualized melanoma combination treatments based on personalized network alterations. Using an information-theoretic approach, we compute high-resolution patient-specific altered signaling signatures. These altered signaling signatures each consist of several co-expressed subnetworks, which should all be targeted to optimally inhibit the entire altered signaling flux. Based on these data, we design smart, personalized drug combinations, often consisting of FDA-approved drugs. We validate our approach in vitro and in vivo showing that individualized drug combinations that are rationally based on patient-specific altered signaling signatures are more efficient than the clinically used anti-BRAFV600E or BRAFV600E/MEK targeted therapy. Furthermore, these drug combinations are highly selective, as a drug combination efficient for one BRAFV600E tumor is significantly less efficient for another, and vice versa. The approach presented herein can be broadly applicable to aid clinicians to rationally design patient-specific anti-melanoma drug combinations.

Self-referencing circular dichroism ion yield measurements for improved statistics using femtosecond laser pulses.

The combination of circular dichroism with laser mass spectrometry via the measurement of ion yields is a powerful tool in chiral recognition, but the measured anisotropies are generally weak. The method presented in this contribution reduces the measurement error significantly. A common path optical setup generates a pair of counter-rotating laser foci in the interaction region of a time-of-flight spectrometer. As the space focus condition is fulfilled for both foci individually, this becomes a twin-peak ion source with well separated and sufficiently resolved mass peaks. The individual control of polarization allows for in situ correction of experimental fluctuations measuring circular dichroism. Our robust optical setup produces reliable and reproducible results and is applicable for dispersion sensitive femtosecond laser pulses. In this contribution, we use 3-methyl-cyclopentanone as a prototype molecule to illustrate the evaluation procedure and the measurement principle.

Combinatorial effects of trans-cinnamaldehyde with fluoride and chlorhexidine on Streptococcus mutans.

AIMS: The aim of this study was to investigate the effects of trans-cinnamaldehyde (TC) and its synergistic activity with chlorhexidine (CHX) and fluoride against Streptococcus mutans. METHODS AND RESULTS: Streptococcus mutans UA159 was treated with TC alone and in combination with CHX or sodium fluoride. The synergy profile was analysed using the Zero Interaction Potency model. TC showed strong synergism (synergy score of 21·697) with CHX, but additive effect (synergy score of 5·298) with fluoride. TC and the combinations were tested for acid production (glycolytic pH drop) and biofilm formation by S. mutans, and nitric oxide production in macrophages. TC significantly inhibited sucrose-dependent biofilm formation and acid production by S. mutans. Mechanistic studies were carried out by qRT-PCR-based transcriptomic studies which showed that TC acts by impairing genes related to metabolism, quorum sensing, bacteriocin expression, stress tolerance and biofilm formation. CONCLUSIONS: trans-Cinnamaldehyde potentiates CHX and sodium fluoride in inhibiting S. mutans biofilms and virulence through multiple mechanisms. This study sheds significant new light on the potential to develop TC as an anti-caries treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: Oral diseases were classified as a 'silent epidemic' in the US Surgeon General's Report on Oral Health. Two decades later, >4 billion people are still affected worldwide by caries, having significant effects on the quality of life. There is an urgent need to develop novel compounds and strategies to combat dental caries. Here, we prove that TC downregulates multiple pathways and potentiates the CHX and fluoride to prevent S. mutans biofilms and virulence. This study sheds significant new light on the potential to develop TC in combination with CHX or fluoride as novel treatments to arrest dental caries.

Peptide decorated glycolipid nanomicelles for drug delivery across the blood-brain barrier (BBB).

This interdisciplinary research highlights the engineering of glycolipid nanomicelles with surface modification using a BBB crossing peptide for in vivo drug delivery especially for glioma therapy. We demonstrated an eco-friendly, green synthesis of a nanomicelle followed by felicitous characterization which substantiates the merits of the drug delivery system.

Ebselen has lithium-like effects on central 5-HT2A receptor function.

BACKGROUND AND PURPOSE: Lithium's antidepressant action may be mediated by inhibition of inositol monophosphatase (IMPase), a key enzyme in Gq -protein coupled receptor signalling. Recently, the antioxidant agent ebselen was identified as an IMPase inhibitor. Here, we investigated both ebselen and lithium in models of the 5-HT2A receptor, a Gq -protein coupled receptor involved in lithium's actions. EXPERIMENTAL APPROACH: 5-HT2A receptor function was assessed in mice by measuring the behavioural (head-twitches, ear scratches) and molecular (cortical immediate early gene [IEG] mRNA; Arc, c-fos, Egr2) responses to 5-HT2A receptor agonists. Ebselen and lithium were administered either acutely or repeatedly prior to assessment of 5-HT2A receptor function. Because lithium and 5-HT2A receptor antagonists augment the action of selective serotonin reuptake inhibitors (SSRIs), ebselen was tested for this activity by co-administration with the SSRI citalopram in microdialysis (extracellular 5-HT) experiments. KEY RESULTS: Acute and repeated administration of ebselen inhibited behavioural and IEG responses to the 5-HT2A receptor agonist DOI. Repeated lithium also inhibited DOI-evoked behavioural and IEG responses. In comparison, a selective IMPase inhibitor (L-690330) attenuated the behavioural response to DOI whereas glycogen synthase kinase inhibitor (AR-A014418) did not. Finally, ebselen enhanced the increase in extracellular 5-HT induced by citalopram, and also increased regional brain 5-HT synthesis. CONCLUSIONS AND IMPLICATIONS: Our data demonstrated lithium-mimetic effects of ebselen in different experimental models of 5-HT2A receptor function, probably mediated by IMPase inhibition. This evidence of lithium-like neuropharmacological effects of ebselen adds further support for the clinical testing of ebselen in mood disorders, including as an antidepressant augmenting agent.

Regulation of monocyte induced cell migration by the RNA binding protein, FXR1.

FXR1 belongs to a family of RNA-binding proteins that play critical roles in post-transcriptional regulation of gene expression in immunity, development and cancer. FXR1 is associated with regulation of specific mRNAs in myocytes and macrophages. In quiescent cells (> 24 h of extended serum-starvation, ∼30-48 h or more), a spliced isoform of FXR1, FXR1a, promotes translation of the cytokine TNFα, independent of the effects of RNA levels. Here we examined the role of FXR1 in THP1 human monocytic leukemic cells that were grown in serum, as well as in early (24 h) serum-starvation conditions that demonstrates differences in gene expression mechanisms and is distinct from quiescent (> 24 h extended serum-starvation) cells. Global RNA profiling, conducted to investigate the role of FXR1 on mRNA levels, revealed that FXR1 affects levels of specific mRNAs in serum-grown and in early 24 h serum-starvation conditions. FXR1 decreases levels of several mRNAs, including as previously identified, CDKN1A (p21CIP1 or p21) mRNA in serum-grown cells. Interestingly, we find that FXR1 positively regulates mRNA levels of specific cytokines and chemokines in serum-grown and in early 24 h serum-starvation conditions. These include IL1ß and CCL2 that control cell migration. Accordingly, depletion and overexpression of FXR1 decreased and increased levels of CCL2 mRNA. Consistent with the reduced levels of IL1ß, CCL2 and other chemokines upon FXR1 depletion, our data reveal that depletion of FXR1 decreases the ability of these cells to induce cell migration of neighboring monocytic cells. These data reveal a new role of FXR1 in controlling induction of monocyte migration.

Brain-computer interface devices for patients with paralysis and amputation: a meeting report.

OBJECTIVE: The Food and Drug Administration's (FDA) Center for Devices and Radiological Health (CDRH) believes it is important to help stakeholders (e.g., manufacturers, health-care professionals, patients, patient advocates, academia, and other government agencies) navigate the regulatory landscape for medical devices. For innovative devices involving brain-computer interfaces, this is particularly important. APPROACH: Towards this goal, on 21 November, 2014, CDRH held an open public workshop on its White Oak, MD campus with the aim of fostering an open discussion on the scientific and clinical considerations associated with the development of brain-computer interface (BCI) devices, defined for the purposes of this workshop as neuroprostheses that interface with the central or peripheral nervous system to restore lost motor or sensory capabilities. MAIN RESULTS: This paper summarizes the presentations and discussions from that workshop. SIGNIFICANCE: CDRH plans to use this information to develop regulatory considerations that will promote innovation while maintaining appropriate patient protections. FDA plans to build on advances in regulatory science and input provided in this workshop to develop guidance that provides recommendations for premarket submissions for BCI devices. These proceedings will be a resource for the BCI community during the development of medical devices for consumers.

Novel dengue virus inhibitor 4-HPR activates ATF4 independent of protein kinase R-like Endoplasmic Reticulum Kinase and elevates levels of eIF2α phosphorylation in virus infected cells.

Infections by dengue virus (DENV) are increasing worldwide, with an urgent need for effective anti-DENV agents. We recently identified N-(4-hydroxyphenyl) retinamide (4-HPR), an anti-DENV agent effective against all 4 serotypes of DENV in cell culture, and in a lethal mouse model for DENV infection (Fraser et al., 2014b). Although identified as an inhibitor of DENV non-structural protein 5 (NS5) recognition by host nuclear import proteins, the precise impact and mode of action of 4-HPR in effecting DENV clearance remains to be defined. Significantly, concurrent with decreased viral RNA and infectious DENV in 4-HPR-treated cells, we previously observed specific up-regulation of transcripts representing the Protein Kinase R-like Endoplasmic Reticulum Kinase (PERK) arm of the unfolded protein response (UPR) pathway upon 4-HPR addition. Here we pursue these findings in detail, examining the role of specific PERK pathway components in DENV clearance. We demonstrate that 4-HPR-induced nuclear localization of Activating Transcription Factor 4 (ATF4), a pathway component downstream from PERK, occurs in a PERK-independent manner, implying activation instead occurs through Integrated Stress Response (ISR) kinases. Significantly, ATF4 does not appear to be required for the antiviral activity of 4-HPR, suggesting transcriptional events induced by ATF4 do not drive the 4-HPR-induced antiviral state. Instead, we demonstrate that 4-HPR induces phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), a target of ISR kinases which controls translation attenuation, and confirm the importance of phosphorylated-eIF2α in DENV infection using guanabenz, a specific inhibitor of eIF2α dephosphorylation. This study provides the first detailed insight into the cellular effects modulated by 4-HPR in DENV-infected cells, critical to progressing 4-HPR towards the clinic.

Farnesol quells oxidative stress, reactive gliosis and inflammation during acrylamide-induced neurotoxicity: Behavioral and biochemical evidence.

Acrylamide (ACR) is an industrial pollutant, to which humans are exposed through chemicals associated with day to day human life and contributes to neurological disorders. The role of reactive gliosis upon toxic insults remains paradoxical, and the immunomodulatory events during ACR intoxication remain obscure. In view of this, the present study investigated ACR-induced (20mg/kgb.wt for 4weeks) neurodegeneration in the context of oxidative stress and associated inflammatory events and the ability of farnesol, a sesquiterpene, to mitigate reactive gliosis in the brain of Swiss albino mice. Farnesol supplementation (100mg/kgb.wt.) showed a marked improvement in gait performance, neuromuscular function and fine motor coordination and attenuated ACR-induced diminution in glutathione (GSH) with parallel reduction in lipid peroxidation (LPO), protein carbonyls, hydroxide, hydroperoxide and nitrite levels. Farnesol treatment significantly ameliorated ACR-mediated histological aberrations and reactive gliosis by downregulating Glial fibrillary acidic protein (GFAP) and Ionizsed calcium-binding adapter molecule-1 ​(Iba-1) in the cortex, hippocampus and striatum. Further, ACR stimulated increase in levels of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß) and inducible form of nitric oxide synthase (iNOS) were considerably decreased by farnesol. In conclusion, our findings indicate that farnesol exerts neuroprotective efficacy during ACR-induced neuropathology by suppressing reactive gliosis and associated inflammatory events.

NSC-87877 inhibits DUSP26 function in neuroblastoma resulting in p53-mediated apoptosis.

Dual specificity protein phosphatase 26 (DUSP26) is overexpressed in high-risk neuroblastoma (NB) and contributes to chemoresistance by inhibiting p53 function. In vitro, DUSP26 has also been shown to effectively inhibit p38 MAP kinase. We hypothesize that inhibiting DUSP26 will result in decreased NB cell growth in a p53 and/or p38-mediated manner. NSC-87877 (8-hydroxy-7-[(6-sulfo-2-naphthyl)azo]-5-quinolinesulfonic acid), a novel DUSP26 small molecule inhibitor, shows effective growth inhibition and induction of apoptosis in NB cell lines. NB cell lines treated with small hairpin RNA (shRNA) targeting DUSP26 also exhibit a proliferation defect both in vitro and in vivo. Treatment of NB cell lines with NSC-87877 results in increased p53 phosphorylation (Ser37 and Ser46) and activation, increased activation of downstream p38 effector proteins (heat shock protein 27 (HSP27) and MAP kinase-activated protein kinase 2 (MAPKAPK2)) and poly ADP ribose polymerase/caspase-3 cleavage. The cytotoxicity resulting from DUSP26 inhibition is partially reversed by knocking down p53 expression with shRNA and also by inhibiting p38 activity with SB203580 (4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine). In an intrarenal mouse model of NB, NSC-87877 treatment results in decreased tumor growth and increased p53 and p38 activity. Together, these results suggest that DUSP26 inhibition with NSC-87877 is an effective strategy to induce NB cell cytotoxicity in vitro and in vivo through activation of the p53 and p38 mitogen-activated protein kinase (MAPK) tumor-suppressor pathways.

A New Classification System for Unilateral Cleft Lip and Palate Infants to assist Presurgical Infant Orthopedics.

The proposed advantages of pre-surgical naso-alveolar moulding (PNAM) are easy primary lip repair which heals under minimum tension reducing the scar formation and improving the aesthetic results in addition to reshaping of alar cartilage and improvement of nasal symmetry.However, the anatomy and alveolar morphology varies for each cleft child; the procedure for PNAM differs accordingly. In an attempt to categorize unilateral cleft lip and palate cases as per anatomical variations, a new classification system has been proposed. This classification aims to give an insight in unilateral cleft morphology based on which modification in PNAM procedure could be done.

A small-molecule inhibitor of UBE2N induces neuroblastoma cell death via activation of p53 and JNK pathways.

Neuroblastoma (NB) is the most common extracranial neoplasm in children. In NB, loss of p53 function is largely due to cytoplasmic sequestration rather than mutation. Ubiquitin-conjugating enzyme E2 N (UBE2N), also known as Ubc13, is an E2 ubiquitin-conjugating enzyme that promotes formation of monomeric p53 that results in its cytoplasmic translocation and subsequent loss of function. Therefore, inhibition of UBE2N may reactivate p53 by promoting its nuclear accumulation. Here, we show that NSC697923, a novel UBE2N inhibitor, exhibits potent cytotoxicity in a panel of NB cell lines evidenced by its ability to induce apoptosis. In p53 wild-type NB cells, NSC697923 induced nuclear accumulation of p53, which led to its increased transcriptional activity and tumor suppressor function. Interestingly, in p53 mutant NB cells, NSC697923 induced cell death by activating JNK pathway. This effect was reversible by blocking JNK activity with its selective inhibitor, SP600125. More importantly, NSC697923 impeded cell growth of chemoresistant LA-N-6 NB cell line in a manner greater than conventional chemotherapy drugs doxorubicin and etoposide. NSC697923 also revealed in vivo antitumor efficacy in NB orthotopic xenografts. Taken together, our results suggest that UBE2N is a potential therapeutic target in NB and provide a basis for the rational use of UBE2N inhibitors like NSC697923 as a novel treatment option for NB patients.

Characterization of NAADP-mediated calcium signaling in human spermatozoa.

Ca(2+) signaling in spermatozoa plays a crucial role during processes such as capacitation and release of the acrosome, but the underlying molecular mechanisms still remain unclear. Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca(2+)-releasing second messenger in a variety of cellular processes. The presence of a NAADP synthesizing enzyme in sea urchin sperm has been previously reported, suggesting a possible role of NAADP in sperm Ca(2+) signaling. In this work we used in vitro enzyme assays to show the presence of a novel NAADP synthesizing enzyme in human sperm, and to characterize its sensitivity to Ca(2+) and pH. Ca(2+) fluorescence imaging studies demonstrated that the permeable form of NAADP (NAADP-AM) induces intracellular [Ca(2+)] increases in human sperm even in the absence of extracellular Ca(2+). Using LysoTracker, a fluorescent probe that selectively accumulates in acidic compartments, we identified two such stores in human sperm cells. Their acidic nature was further confirmed by the reduction in staining intensity observed upon inhibition of the endo-lysosomal proton pump with Bafilomycin, or after lysosomal bursting with glycyl-l-phenylalanine-2-naphthylamide. The selective fluorescent NAADP analog, Ned-19, stained the same subcellular regions as LysoTracker, suggesting that these stores are the targets of NAADP action.

Current status of presurgical infant orthopaedic treatment for cleft lip and palate patients: A critical review.

Rehabilitation of cleft lip and palate (CLP) patients is a challenge for all the concerned members of the cleft team, and various treatment modalities have been attempted to obtain aesthetic results. Presurgical infant orthopaedics (PSIO) was introduced to reshape alveolar and nasal segments prior to surgical repair of cleft lip. However, literature reports lot of controversy regarding the use of PSIO in patients with CLP. Evaluation of long-term results of PSIO can provide scientific evidence on the efficacy and usefulness of PSIO in CLP patients. The aim was to assess the scientific evidence on the efficiency of PSIO appliances in patients with CLP and to critically analyse the current status of PSIO. A PubMed search was performed using the terms PSIO, presurgical nasoalveolar moulding and its long-term results and related articles were selected for the review. The documented studies report no beneficial effect of PSIO on maxillary arch dimensions, facial aesthetics and in the subsequent development of dentition and occlusion in CLP patients. Nasal moulding seems to be more beneficial and effective in unilateral cleft lip and palate patients with better long-term results.

Chronic sensory-motor activity in behaving animals using regenerative multi-electrode interfaces.

Regenerative peripheral nerve interfaces have been proposed as viable alternatives for the natural control and feel of robotic prosthetic limbs. We have developed a Regenerative Multi-electrode Interface (REMI) that guides re-growing axons through an electrode array deployed in the lumen of a nerve guide. While acute studies have shown the use of the REMI in the rat sciatic nerve, the quality of chronic signal recording has not been reported. Here we show that implantation of this interface in the sciatic nerve is stable with high quality recordings up to 120 days and failures mainly attributable to abiotic factors related to pedestal detachment and wire breakage. We further tested the interfacing of REMI with fascicles of the sciatic nerve that primarily innervate muscles (tibial) and skin (sural). When implanted into the tibial nerve, bursting activity was observed synchronous to stepping. However, implantation of REMI into the sural nerve failed due to its small size. While fascicles smaller than 300 µm are a challenge for regenerative interfacing, we show that a modified REMI can be used in an insertion mode to record sensory signals from skin. In summary, the REMI represents an effective tool for recording firing patterns of specific axon types during voluntary movement, which may be used to improve the motor control and sensory feedback in closed loop control systems for robotic prosthesis.