Alternative muscle synergy patterns of upper limb amputees.

Myoelectric hand prostheses are effective tools for upper limb amputees to regain hand functions. Much progress has been made with pattern recognition algorithms to recognize surface electromyography (sEMG) patterns, but few attentions was placed on the amputees' motor learning process. Many potential myoelectric prostheses users could not fully master the control or had declined performance over time. It is possible that learning to produce distinct and consistent muscle activation patterns with the residual limb could help amputees better control the myoelectric prosthesis. In this study, we observed longitudinal effect of motor skill learning with 2 amputees who have developed alternative muscle activation patterns in response to the same set of target prosthetic actions. During a 10-week program, amputee participants were trained to produce distinct and constant muscle activations with visual feedback of live sEMG and without interaction with prosthesis. At the end, their sEMG patterns were different from each other and from non-amputee control groups. For certain intended hand motion, gradually reducing root mean square (RMS) variance was observed. The learning effect was also assessed with a CNN-LSTM mixture classifier designed for mobile sEMG pattern recognition. The classification accuracy had a rising trend over time, implicating potential performance improvement of myoelectric prosthesis control. A follow-up session took place 6 months after the program and showed lasting effect of the motor skill learning in terms of sEMG pattern classification accuracy. The results indicated that with proper feedback training, amputees could learn unique muscle activation patterns that allow them to trigger intended prosthesis functions, and the original motor control scheme is updated. The effect of such motor skill learning could help to improve myoelectric prosthetic control performance.

A comparative review of adenovirus A12 and C5 oncogenes.

Oncogenic viruses contribute to 15% of global human cancers. To achieve that, virus-encoded oncoproteins deregulate cellular transcription, antagonize common cellular pathways, and thus drive cell transformation. Notably, adenoviruses were the first human viruses proven to induce cancers in diverse animal models. Over the past decades, human adenovirus (HAdV)-mediated oncogenic transformation has been pivotal in deciphering underlying molecular mechanisms. Key adenovirus oncoproteins, encoded in early regions 1 (E1) and 4 (E4), co-ordinate these processes. Among the different adenovirus species, the most extensively studied HAdV-C5 displays lower oncogenicity than HAdV-A12. A complete understanding of the different HAdV-A12 and HAdV-C5 oncoproteins in virus-mediated cell transformation, as summarized here, is relevant for adenovirus research and offers broader insights into viral transformation and oncogenesis.

Hybrid approach in sacral sore management with maggot debridement therapy and flap reconstruction.

Sacral sore is a common problem in patients with spinal cord injury. It leads to prolonged hospitalization and recurrent infections which might require repeated surgery to treat. Flap reconstruction allows soft tissue coverage of sacral sore under the premise of infection-free wound base. Maggot debridement therapy (MDT) has been described as an alternative non-surgical management as opposed to the traditional surgical debridement in case of infected sore, reducing number of surgeries under anaesthesia. However, MDT and surgery are not mutually exclusive. In this article we describe a hybrid approach combining MDT and flap reconstruction with multi-disciplinary effort in management of sacral sore, which accelerates wound healing and prevents morbidities, while lowering the risks associated with repeated surgical debridement at the same time.

The adenovirus DNA-binding protein DBP.

Adenoviruses are a group of double-stranded DNA viruses that can mainly cause respiratory, gastrointestinal, and eye infections in humans. In addition, adenoviruses are employed as vector vaccines for combatting viral infections, including SARS-CoV-2, and serve as excellent gene therapy vectors. These viruses have the ability to modulate the host cell machinery to their advantage and trigger significant restructuring of the nuclei of infected cells through the activity of viral proteins. One of those, the adenovirus DNA-binding protein (DBP), is a multifunctional non-structural protein that is integral to the reorganization processes. DBP is encoded in the E2A transcriptional unit and is highly abundant in infected cells. Its activity is unequivocally linked to the formation, structure, and integrity of virus-induced replication compartments, molecular hubs for the regulation of viral processes, and control of the infected cell. DBP also plays key roles in viral DNA replication, transcription, viral gene expression, and even host range specificity. Notably, post-translational modifications of DBP, such as SUMOylation and extensive phosphorylation, regulate its biological functions. DBP was first investigated in the 1970s, pioneering research on viral DNA-binding proteins. In this literature review, we provide an overview of DBP and specifically summarize key findings related to its complex structure, diverse functions, and significant role in the context of viral replication. Finally, we address novel insights and perspectives for future research.

Central Sensitization in Patients with Chronic Pain Secondary to Carpal Tunnel Syndrome and Determinants.

Purpose: Central sensitization (CS) is commonly seen in chronic pain disorders, including neuropathic pain. However, there exist inconsistencies concerning the presence of CS in chronic pain secondary to carpal tunnel syndrome (CTS). CS and neuropathic pain manifestations in CTS remain not well established. Therefore, this study aims to investigate the CS and pain profiles in patients with CTS and to explore the potential determinants associated with CS. Patients and Methods: Patients with suspected CTS symptoms lasting 3 months or above and healthy controls were enrolled. History, physical examinations, and nerve conduction studies were employed to confirm the diagnosis and severity of median nerve dysfunction. The central sensitization inventory (CSI) was used to screen CS. Other outcomes included neuropathic pain, CTS-specific symptom severity and functions, emotion, and health-related quality of life. Between-group comparisons were conducted in terms of the CS presence. Logistic regression analysis was performed to identify determinants associated with CS. Results: Over 60% of participants with CTS were found with clinical CS, significantly higher than that in the control group. More than 70% of the CTS participants were identified to have possible or very likely neuropathic pain components. In addition, one-fourth of CTS cases had depression or anxiety. Anxiety was associated with an increased risk of developing CS in CTS (adjusted OR=1.31, 95% CI 1.08-1.59), whereas higher self-perceived general health rating was negatively associated with the presence of CS (adjusted OR=0.92, 95% CI 0.88-0.97) in the multivariate adjusted regression model. Conclusion: CS is prevalent in patients with CTS. Predominant neuropathic pain characteristics were uncovered in CTS patients as well as comorbid psychological distress. Significant association was found between anxiety and CS presence. Self-perceived general health was inversely related to CS. Further research is warranted to explore the mechanisms of anxiety and central pain processing in painful entrapment neuropathy.

Identification of Adenovirus E1B-55K Interaction Partners through a Common Binding Motif.

The adenovirus C5 E1B-55K protein is crucial for viral replication and is expressed early during infection. It can interact with E4orf6 to form a complex that functions as a ubiquitin E3 ligase. This complex targets specific cellular proteins and marks them for ubiquitination and, predominantly, subsequent proteasomal degradation. E1B-55K interacts with various proteins, with p53 being the most extensively studied, although identifying binding sites has been challenging. To explain the diverse range of proteins associated with E1B-55K, we hypothesized that other binding partners might recognize the simple p53 binding motif (xWxxxPx). In silico analyses showed that many known E1B-55K binding proteins possess this amino acid sequence; therefore, we investigated whether other xWxxxPx-containing proteins also bind to E1B-55K. Our findings revealed that many cellular proteins, including ATR, CHK1, USP9, and USP34, co-immunoprecipitate with E1B-55K. During adenovirus infection, several well-characterized E1B-55K binding proteins and newly identified interactors, including CSB, CHK1, and USP9, are degraded in a cullin-dependent manner. Notably, certain binding proteins, such as ATR and USP34, remain undegraded during infection. Structural predictions indicate no conservation of structure around the proposed binding motif, suggesting that the interaction relies on the correct arrangement of tryptophan and proline residues.

Adenovirus E1B-55K controls SUMO-dependent degradation of antiviral cellular restriction factors.

IMPORTANCE: Human adenoviruses (HAdVs) generally cause mild and self-limiting diseases of the upper respiratory and gastrointestinal tracts but pose a serious risk to immunocompromised patients and children. Moreover, they are widely used as vectors for vaccines and vector-based gene therapy approaches. It is therefore vital to thoroughly characterize HAdV gene products and especially HAdV virulence factors. Early region 1B 55 kDa protein (E1B-55K) is a multifunctional HAdV-encoded oncoprotein involved in various viral and cellular pathways that promote viral replication and cell transformation. We analyzed the E1B-55K dependency of SUMOylation, a post-translational protein modification, in infected cells using quantitative proteomics. We found that HAdV increases overall cellular SUMOylation and that this increased SUMOylation can target antiviral cellular pathways that impact HAdV replication. Moreover, we showed that E1B-55K orchestrates the SUMO-dependent degradation of certain cellular antiviral factors. These results once more emphasize the key role of E1B-55K in the regulation of viral and cellular proteins in productive HAdV infections.

The human adenovirus E1B-55K oncoprotein coordinates cell transformation through regulation of DNA-bound host transcription factors.

The multifunctional adenovirus E1B-55K oncoprotein can induce cell transformation in conjunction with adenovirus E1A gene products. Previous data from transient expression studies and in vitro experiments suggest that these growth-promoting activities correlate with E1B-55K-mediated transcriptional repression of p53-targeted genes. Here, we analyzed genome-wide occupancies and transcriptional consequences of species C5 and A12 E1B-55Ks in transformed mammalian cells by combinatory ChIP and RNA-seq analyses. E1B-55K-mediated repression correlates with tethering of the viral oncoprotein to p53-dependent promoters via DNA-bound p53. Moreover, we found that E1B-55K also interacts with and represses transcription of numerous p53-independent genes through interactions with transcription factors that play central roles in cancer and stress signaling. Our results demonstrate that E1B-55K oncoproteins function as promiscuous transcriptional repressors of both p53-dependent and -independent genes and further support the model that manipulation of cellular transcription is central to adenovirus-induced cell transformation and oncogenesis.

The adenoviral E4orf3/4 is a regulatory polypeptide with cell transforming properties in vitro.

The human adenovirus species C type 5 (HAdV-C5) early region 4 (E4) encodes several distinct polypeptides, defined as E4orf1 to E4orf6/7 according to the order and arrangement of the corresponding open reading frames (ORFs). All E4 gene products operate through a complex network of interactions with key viral and cellular regulatory proteins involved in transcription, apoptosis, cell cycle control, and DNA repair. Here, we generated a set of virus mutants carrying point mutations in the individual E4 genes. The phenotypic characterizations of these mutants revealed that mutations of these ORFs had no or only moderate effects on virus replication. Even a triple mutant that fails to produce E4orf3, E4orf4, and the yet uncharacterized alternatively spliced E4orf3/4 fusion protein, was replicating to wild type levels. The E4orf3/4 protein consists of the N-terminal 33 amino acid residues from E4orf3 and the C-terminal 28 amino acid residues from E4orf4. Intriguingly, we found that, similar to E4orf3, E4orf3/4 possesses properties that support the E1A/E1B-induced transformation of primary rodent cells. These results identify and functionally characterize E4orf3/4 and conclude that E4orf3/4 is another E4 region protein that is dispensable for virus replication but promotes the E1A/E1B-induced transformation of primary rodent cells.

Global Transcriptome Analyses of Cellular and Viral mRNAs during HAdV-C5 Infection Highlight New Aspects of Viral mRNA Biogenesis and Cytoplasmic Viral mRNA Accumulations.

It is well established that human adenoviruses such as species C, types 2 and 5 (HAdV-C2 and HAdV-C5), induce a nearly complete shutoff of host-cell protein synthesis in the infected cell, simultaneously directing very efficient production of viral proteins. Such preferential expression of viral over cellular genes is thought to be controlled by selective nucleocytoplasmic export and translation of viral mRNA. While detailed knowledge of the regulatory mechanisms responsible for the translation of viral mRNA is available, the viral or cellular mechanisms of mRNA biogenesis are not completely understood. To identify parameters that control the differential export of viral and cellular mRNAs, we performed global transcriptome analyses (RNAseq) and monitored temporal nucleocytoplasmic partitioning of viral and cellular mRNAs during HAdV-C5 infection of A549 cells. Our analyses confirmed previously reported features of the viral mRNA expression program, as a clear shift in viral early to late mRNA accumulation was observed upon transition from the early to the late phase of viral replication. The progression into the late phase of infection, however, did not result in abrogation of cellular mRNA export; rather, viral late mRNAs outnumbered viral early and most cellular mRNAs by several orders of magnitude during the late phase, revealing that viral late mRNAs are not selectively exported but outcompete cellular mRNA biogenesis.

Promising results in a 3-year follow-up for adults undergoing a one-stage surgery for residual talipes equinovarus as part of a humanitarian mission in Vietnam.

BACKGROUND: Rigid talipes equinovarus (TEV) is a complex foot deformity in which the foot is fixed in a plantarflexed, inverted, and adducted position. This pathology has the potential to severely limit basic life activities, which can be devastating for patients in developing countries. The objective of this study was to present the outcomes of patients with mature bones presenting with severe rigid TEV deformity who were operated on during a humanitarian mission to Vietnam using a single lateral approach and a simple and inexpensive fixation technique. METHODS: This is a retrospective analysis of prospectively collected data. We analyzed the outcomes of patients who underwent surgery for a severe rigid TEV that prevented them from walking minimal distances unaided. All feet were fixed in a non-plantigrade position. The surgeries were conducted as part of two International Extremity Project (IEP) missions in Can Tho, Vietnam (2013 and 2018). Pre- and post-operative AOFAS scores were compared using the paired sample t-test. RESULTS: We operated on 14 feet of 12 patients, 6 (50%) of whom were males, aged 34.42 ± 11.7 (range 12 to 58). Four patients were followed for three months, two patients were followed for 12 months, and eight patients were followed for three years. On the final follow-up visit of each patient, all 14 operated feet were plantigrade with good alignment, and patients reported an improvement in daily activity. After 3 years of follow-up, the mean AOFAS score of eight patients with available data improved by 42.88 ± 3.91 points (95% CI 39.61 to 46.14, P < 0.01). Our patients also reported an improvement in mobility. At the final follow-up examination, no recurrence of the deformity was observed in any of the patients. CONCLUSIONS: Using low-technical surgical modalities, we were able to achieve plantigrade and walkable feet in patients with mature bones who had fixed rigid equinovarus. LEVEL OF EVIDENCE: Level IV- Case Series.

A Single Amino Acid Switch in the Adenoviral DNA Binding Protein Abrogates Replication Center Formation and Productive Viral Infection.

Adenoviruses are very efficient high-capacity vaccine vectors and are common gene delivery systems. Despite their extensive use in preclinical models and clinical trials over the past decades, adenoviral vectors still require optimization. To achieve that, more thorough characterizations of adenoviral genes and gene products, as well as pathogen-host interactions, are indispensable. The adenoviral DNA binding protein (DBP) is a key regulatory protein involved in various cellular and viral processes. Here, we show that single amino acid exchange mutations in human adenovirus C5 (HAdV-C5) DBP strongly influence adenoviral replication by altering interaction with the cellular ubiquitination machinery. Specifically, phenotypic analyses of DBP mutants demonstrate that single amino acid substitutions can regulate interactions with the cellular USP7 deubiquitinase, impede viral DNA synthesis, and completely abolish viral late protein expression and progeny production. Importantly, cells infected with the DBP mutant UBM5 consistently lack DBP-positive replication centers (RCs), which are usually formed during the transition from the early to the late phase of infection. Our findings demonstrate that DBP regulates a key step at the onset of the late phase of infection and that this activity is unambiguously linked to the formation and integrity of viral RCs. These data provide the experimental basis for future work that targets DBP and its interference with the formation of viral RCs during productive infection. Consequently, this work will have immediate impact on DNA virus and adenovirus research in general and, potentially, also on safety optimization of existing and development of novel adenoviral vectors and anti-adenoviral compounds. IMPORTANCE To further understand the biology of human adenoviruses (HAdVs) and to optimize HAdVs for use in prophylactic and therapeutic therapies, a thorough understanding of key viral proteins is paramount. As one of the essential HAdV proteins, the DNA binding protein DBP plays important roles in various steps of the viral replication cycle. In this work, we aimed at deciphering the role of single amino acid exchange mutations in the HAdV-C5 DBP on interaction with the cellular deubiquitinase USP7 and regulation of viral replication. We identify interaction with USP7, viral replication center formation, and viral progeny production as potently regulated steps of the viral life cycle that are affected by these few and distinct mutations in DBP.

Protein-Protein Interactions Facilitate E4orf6-Dependent Regulation of E1B-55K SUMOylation in HAdV-C5 Infection.

The human adenovirus type C5 (HAdV-C5) E1B-55K protein is a multifunctional regulator of HAdV-C5 replication, participating in many processes required for maximal virus production. Its multifunctional properties are primarily regulated by post-translational modifications (PTMs). The most influential E1B-55K PTMs are phosphorylation at highly conserved serine and threonine residues at the C-terminus, and SUMO conjugation to lysines 104 (K104) and 101 (K101) situated in the N-terminal region of the protein, which have been shown to regulate each other. Reversible SUMO conjugation provides a molecular switch that controls key functions of the viral protein, including intracellular trafficking and viral immune evasion. Interestingly, SUMOylation at SUMO conjugation site (SCS) K104 is negatively regulated by another multifunctional HAdV-C5 protein, E4orf6, which is known to form a complex with E1B-55K. To further evaluate the role of E4orf6 in the regulation of SUMO conjugation to E1B-55K, we analyzed different virus mutants expressing E1B-55K proteins with amino acid exchanges in both SCS (K101 and K104) in the presence or absence of E4orf6. We could exclude phosphorylation as factor for E4orf6-mediated reduction of E1B-55K SUMOylation. In fact, we demonstrate that a direct interaction between E1B-55K and E4orf6 is required to reduce E1B-55K SUMOylation. Additionally, we show that an E4orf6-mediated decrease of SUMO conjugation to K101 and K104 result in impaired co-localization of E1B-55K and SUMO in viral replication compartments. These findings indicate that E4orf6 inhibits E1B-55K SUMOylation, which could favor assembly of E4orf6-dependent E3 ubiquitin ligase complexes that are known to degrade a variety of host restriction factors by proteasomal degradation and, thereby, promote viral replication.

Cultural Validation of the Chinese Central Sensitization Inventory in Patients with Chronic Pain and its Predictive Ability of Comorbid Central Sensitivity Syndromes.

BACKGROUND: Central sensitization (CS) is frequently reported in chronic pain, and the central sensitization inventory (CSI) is popularly used to assess CS. However, a validated Chinese CSI is lacking and its predictive ability for the comorbidity of central sensitivity syndromes (CSSs) remains unclear. Hence, this study aimed to generate the Chinese CSI (CSI-C) with cultural adaptation and examine its psychometric properties. METHODS: The CSI-C was formulated through forward and backward translation, panel review and piloting and then validated among patients with chronic pain (n = 235). Its internal consistency, test-retest reliability, and concurrent validity were measured. An exploratory factor analysis (EFA) was performed for the construct validity. Receiver operating characteristic (ROC) analysis was employed to determine the discriminative ability in the presence of comorbidity of CSSs. RESULTS: About 70% of the participants in the study experienced at least mild CS symptoms. CSI-C demonstrates a high internal consistency (Cronbach's alpha = 0.896) and excellent test-retest reliability (ICC = 0.932). CSI-C scoring was significantly correlated with pain intensity (r = 0.188), EQ-5D index (r = -0.375), anxiety (r=0.525), and depression (r = 0.467). The EFA generated a 5-factor model, including physical symptoms, emotional distress, hypersensitivity syndromes and so on. An CSI cutoff of 42 had a sensitivity of 71.4% and a specificity of 70% for identifying chronic pain patients with ≥2 CSSs. CONCLUSION: The CS manifestations are prevalent in those with persistent pain. CSI-C is a reliable and valid instrument for measuring CS. A CSI score ≥42 may predict the comorbidity of 2 or above CSSs in patients with chronic pain.

GAUSS - genesis of asteroids and evolution of the solar system: A sample return mission to Ceres.

The goal of Project GAUSS (Genesis of Asteroids and evolUtion of the Solar System) is to return samples from the dwarf planet Ceres. Ceres is the most accessible candidate of ocean worlds and the largest reservoir of water in the inner Solar System. It shows active volcanism and hydrothermal activities in recent history. Recent evidence for the existence of a subsurface ocean on Ceres and the complex geochemistry suggest past habitability and even the potential for ongoing habitability. GAUSS will return samples from Ceres with the aim of answering the following top-level scientific questions: What is the origin of Ceres and what does this imply for the origin of water and other volatiles in the inner Solar System?What are the physical properties and internal structure of Ceres? What do they tell us about the evolutionary and aqueous alteration history of dwarf planets?What are the astrobiological implications of Ceres? Is it still habitable today?What are the mineralogical connections between Ceres and our current collections of carbonaceous meteorites?

Are mindfulness treatments effective for pain in cancer patients? A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Mindfulness-based interventions (MBIs) have been recently applied in pain management and cancer care. However, inconsistencies exist concerning the effectiveness of MBIs on pain control among cancer patients. Therefore, this study aimed to examine the efficacy of MBIs on pain in cancer patients via a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: Databases (MEDLINE, PubMed, Embase, CINAHL, PsycINFO, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) were searched using key terms related to pain, cancer and mindfulness. The primary outcome was pain intensity. Standardized mean difference (SMD) of each outcome with 95% confidence interval (95% CI) was calculated. The quality of evidence was assessed by GRADE assessment. RESULTS: Ten RCTs with 843 participants were included. Significant pooled effects of MBIs on pain intensity were found at both short-term (SMD = -0.19, 95% CI [-0.33 to -0.04]) and long-term (SMD = -0.20, 95% CI [-0.35 to -0.05]) follow-up, whereas no significance was observed for pain interference. In subgroup analyses, significant intervention effects were only seen in clinic-based MBIs compared to remote MBIs, and pooled effects of MBIs in attenuating pain were discovered relative to passive rather than active comparators. GRADE ratings showed moderate certainty of evidence in MBIs for pain intensity but low for pain interference. CONCLUSIONS: The efficacy of MBIs in reducing pain intensity among cancer patients was revealed in this meta-analysis, albeit with a small effect size. Future research is warranted to optimize mindfulness treatment for pain control in cancer patients with high methodological quality and a large sample size. SIGNIFICANCE: The effect of MBIs on pain in cancer patients was demonstrated in our analysis, albeit with small effect sizes. High-quality RCTs are needed to verify the efficacy of MBIs on cancer patients or survivors with pain complaints. Future trials should take into account the specific pain outcome measures (pain intensity or pain interference), the approach of intervention provision (clinic-based or remote MBI, group or individual practice), the duration and frequency of interventions and the comparators (passive or active control arms).

Conserved E1B-55K SUMOylation in Different Human Adenovirus Species Is a Potent Regulator of Intracellular Localization.

Over the past decades, studies on the biology of human adenoviruses (HAdVs) mainly focused on the HAdV prototype species C type 5 (HAdV-C5) and revealed fundamental molecular insights into mechanisms of viral replication and viral cell transformation. Recently, other HAdV species are gaining more and more attention in the field. Reports on large E1B proteins (E1B-55K) from different HAdV species showed that these multifactorial proteins possess strikingly different features along with highly conserved functions. In this work, we identified potential SUMO-conjugation motifs (SCMs) in E1B-55K proteins from HAdV species A to F. Mutational inactivation of these SCMs demonstrated that HAdV E1B-55K proteins are SUMOylated at a single lysine residue that is highly conserved among HAdV species B to E. Moreover, we provide evidence that E1B-55K SUMOylation is a potent regulator of intracellular localization and p53-mediated transcription in most HAdV species. We also identified a lysine residue at position 101 (K101), which is unique to HAdV-C5 E1B-55K and specifically regulates its SUMOylation and nucleo-cytoplasmic shuttling. Our findings reveal important new aspects on HAdV E1B-55K proteins and suggest that different E1B-55K species possess conserved SCMs while their SUMOylation has divergent cellular effects during infection. IMPORTANCE E1B-55K is a multifunctional adenoviral protein and its functions are highly regulated by SUMOylation. Although functional consequences of SUMOylated HAdV-C5 E1B-55K are well studied, we lack information on the effects of SUMOylation on homologous E1B-55K proteins from other HAdV species. Here, we show that SUMOylation is a conserved posttranslational modification in most of the E1B-55K proteins, similar to what we know about HAdV-C5 E1B-55K. Moreover, we identify subcellular localization and regulation of p53-dependent transcription as highly conserved SUMOylation-regulated E1B-55K functions. Thus, our results highlight how HAdV proteins might have evolved in different HAdV species with conserved domains involved in virus replication and differing alternative functions and interactions with the host cell machinery. Future research will link these differences and similarities to the diverse pathogenicity and organ tropism of the different HAdV species.

Animal Models in Human Adenovirus Research.

Human adenovirus (HAdV) infections cause a wide variety of clinical symptoms, ranging from mild upper respiratory tract disease to lethal outcomes, particularly in immunocompromised individuals. To date, neither widely available vaccines nor approved antiadenoviral compounds are available to efficiently deal with HAdV infections. Thus, there is a need to thoroughly understand HAdV-induced disease, and for the development and preclinical evaluation of HAdV therapeutics and/or vaccines, and consequently for suitable standardizable in vitro systems and animal models. Current animal models to study HAdV pathogenesis, persistence, and tumorigenesis include rodents such as Syrian hamsters, mice, and cotton rats, as well as rabbits. In addition, a few recent studies on other species, such as pigs and tree shrews, reported promising data. These models mimic (aspects of) HAdV-induced pathological changes in humans and, although they are relevant, an ideal HAdV animal model has yet to be developed. This review summarizes the available animal models of HAdV infection with comprehensive descriptions of virus-induced pathogenesis in different animal species. We also elaborate on rodent HAdV animal models and how they contributed to insights into adenovirus-induced cell transformation and cancer.

Can Tho Transfer Technique: Extensor Hallucis Longus to Tibialis Anterior Tenodesis for Footdrop.

BACKGROUND: Footdrop, or the inability to actively dorsiflex the foot, may result from numerous pathologic conditions, including poliomyelitis and cerebral palsy. Although the gait of patients with footdrop can be improved by performing an extensor hallucis longus (EHL) to tibialis anterior (TA) tendon transfer, the success rate of this procedure is relatively low. METHODS: Seven paralytic patients with footdrop were surgically treated using a new buttonhole-type technique that involves passing a loop of the EHL through a TA split using umbilical tape and suturing at the four corners of the EHL attaching to the TA while the foot is dorsiflexed. RESULTS: Eight years after surgery, all three patients who were available for follow-up displayed active dorsiflexion, improved mobility, and a palpable TA-EHL tenodesis, with no cockup deformity. CONCLUSIONS: This new approach, which we term Can Tho transfer, improves the mechanical strength of TA-EHL tenodesis.

Differential Regulation of Cellular FAM111B by Human Adenovirus C Type 5 E1 Oncogenes.

The adenovirus type 5 (HAdV-C5) E1 transcription unit encodes regulatory proteins that are essential for viral replication and transformation. Among these, E1A and E1B-55K act as key multifunctional HAdV-C5 proteins involved in various steps of the viral replication cycle and in virus-induced cell transformation. In this context, HAdV-C5-mediated dysregulations of cellular factors such as the tumor suppressors p53 and pRB have been intensively investigated. However, cellular components of downstream events that could affect infection and viral transformation are widely unknown. We recently observed that cellular FAM111B is highly regulated in an E1A-dependent fashion. Intriguingly, previous reports suggest that FAM111B might play roles in tumorigenesis, but its exact functions are not known to date. Here, we set out to investigate the role of FAM111B in HAdV-C5 infections. We found that (i) FAM111B levels are upregulated early and downregulated late during infection, that (ii) FAM111B expression is differentially regulated, that (iii) FAM111B expression levels depend on the presence of E1B-55K and E4orf6 and that (iv) a FAM111B knockdown increases HAdV-C5 replication. Our data indicate that FAM111B acts as an anti-adenoviral host factor that is involved in host cell defense mechanisms in productive HAdV-C5 infection. Moreover, these findings suggest that FAM111B might play an important role in the host antiviral immune response that is counteracted by HAdV-C5 E1B-55K and E4orf6 oncoproteins.