Use of scapular tip flaps in the reconstruction of head and neck defects: a systematic review and meta-analysis.

Scapular tip flaps (STF) may be used as an alternative to traditional methods of reconstruction of head and neck cancer (HNC) defects. This study aimed to establish the success and complication rates for STF in HNC reconstruction. A literature search was conducted on PubMed, BMJ Journals, DARE, EMBASE databases and Cochrane (CENTRAL) register. (Registry CRD42023428012). A total of 23 studies fulfilled the inclusion criteria with 474 patients who underwent reconstructive procedures using the STF. 100% of STF used were free flaps (STFFs). The most common reason for reconstruction was following malignancy (81.4%, n = 386). The pooled success rates in all studies using scapular tip flaps in head and neck reconstruction was 99% (95% CI, 97 to 100, p = 1.00; I2 = 0). Pooled total complication rates were 38% (95% CI, 25 to 51, p < 0.01; I2 = 90%). 19.6% required return to theatre with only 1.5% being for repeat flap coverage. The STF demonstrated an overall success rate of 99%. This is higher than other documented success rates with mainstay flaps for HNC defect reconstruction. Complication and re-operation rates were also like recorded rates. This review demonstrates the advantage of STF as a safe and versatile reconstructive option for HNC related defects. Evaluation of the literature is limited by poor-quality studies and comparability bias.

Making physical activity fun and accessible to adults with intellectual disabilities: A pilot study of a gamification intervention.

BACKGROUND: Only about 9% of individuals with intellectual disabilities reach the government's physical activity (PA) recommendations. Combining gamification and technology seems particularly promising in overcoming personal and environmental barriers to PA participation. METHOD: Eighteen adults with varying levels of intellectual disabilities completed a pilot study to assess the initial effects of a cycling gamification intervention on levels of PA, fitness, psychosocial outcomes, and challenging behaviours. The study comprised three designs: pre-post single group, AB single-case, and qualitative. Social validity, implementation barriers and facilitators were also explored. RESULTS: Nearly all 18 participants cycled daily. Time and distance cycled daily increase during the intervention while a decrease in stereotyped behaviours was observed. Participants and staff found the intervention enjoyable and socially valid. CONCLUSIONS: Results of the multiple-design study suggest that gamification interventions may be a suitable, enjoyable, and promising way to contribute to PA participation of adults with intellectual disabilities.

Autologous breast reconstruction in low- and middle-income countries (LMICs): a systematic review of current practices and challenges.

INTRODUCTION: Efforts to improve global healthcare persist, yet LMICs face challenges accessing surgical care, especially breast reconstruction amidst rising breast cancer cases. This review evaluates the present state and challenges of autologous breast reconstruction in low- and middle-income countries (LMICs). EVIDENCE ACQUISITION: Utilizing the PRISMA guidelines and the Cochrane Collaboration's standards, databases such as EMBASE, MEDLINE, Cochrane, PubMed, and Google Scholar were examined for studies on breast reconstruction in LMICs (based on the World Bank's 2022-2023 definitions) up to August 2022. Articles and case reports focusing on autologous reconstruction following breast cancer surgery in these regions were incorporated. EVIDENCE SYNTHESIS: From an initial 288 articles, 19 met the criteria after thorough assessment. These articles documented 4899 patient cases from LMICs, with the breakdown being: 11 on LD flaps, nine on TRAM flaps, eight on DIEP flaps, two on TDAP flaps, and one on TMG flap. Flap necrosis emerged as the prevalent complication in four studies. CONCLUSIONS: While autologous breast reconstruction presents superior aesthetic benefits without notable long-term economic setbacks, its adoption in LMICs is limited. This is partly due to the domination of implant-based methods among patients and surgeons, selected due to convenience. The scarcity of concrete evidence and standardized metrics in LMICs clouds the understanding of this procedure. Despite its advantages, awareness is low, necessitating more training and awareness campaigns. Uniform reporting, quality data, and financial analysis can provide a comprehensive LMIC understanding, aiding future research.

Use of supermicrosurgery in craniofacial and head and neck soft tissue reconstruction: a systematic review of the literature and meta-analysis.

Supermicrosurgery is an evolving approach in the reconstruction of head and neck (HN) and craniofacial (CF) defects. This systematic review aims to evaluate the use of supermicrosurgery for arterial or combined arterial and venous anastomoses in the reconstruction of HN and CF soft tissue defects, and the associated success, total complication, and reoperation rates. A literature search was conducted on PubMed, Dynamed, DARE, EMBASE, Cochrane, and British Medical Journal (BMJ) electronic databases (PROSPERO ID: CRD42023476825). Nine studies fulfilled the inclusion criteria with 35 patients who underwent soft tissue reconstructive procedures using supermicrosurgery. Twenty-one flaps were performed on 20 patients (57.1%) with the remaining 15 patients (42.9%) undergoing supermicrosurgical replantation. The most common pathology requiring reconstruction was HN trauma (n = 16, 45.7%) followed by malignancy (n = 15, 42.9%). The pooled success rate for supermicrosurgery was 98% (95% CI 90 to 100, p = 1.00; I2 = 0%). The cumulative complication rate across all the studies was 46% (95% CI 13 to 80, p < 0.01; I2 = 0%), and the pooled rate of reoperation was 1% (95% CI 0 to 8, p = 0.23; I2 = 24%). The use of supermicrosurgery for HN and CF soft tissue reconstruction has an overall success rate of 98%, which is commensurate with traditional microsurgery for HN reconstruction. Complication and reoperation rates are comparable to previous literature. This study confirms the feasibility of supermicrosurgery as a safe and reliable reconstructive option for HN and CF defects.

Patient satisfaction with telehealth vs in-person hand therapy: A retrospective review of results of an online satisfaction survey.

BACKGROUND: The COVID-19 pandemic necessitated a shift from in-person to telehealth visits in many outpatient rehabilitation facilities. PURPOSE: To determine whether patients reported similar levels of satisfaction receivingtelehealth hand therapy as when receiving in-person hand therapy. STUDY DESIGN: Retrospective review of patient satisfaction surveys. METHODS: Satisfaction surveys were reviewed retrospectively among patients who participated in in-person hand therapy between April 21 and October 21, 2019, or after participating in telehealth hand therapy between April 21 and October 21, 2020. Information on gender, age, insurance provider, postoperative status and comments were also collected. Kruskal-Wallis tests were used to compare survey scores between groups. Chi -squared tests were used to compare categorical patient characteristics between groups. RESULTS: A total of 288 surveys were included: 121 surveys for in-person evaluations, 53 surveys for in-person follow-up visits, 55 surveys for telehealth evaluations and 59 surveys for telehealth follow-up visits. No significant differences in satisfaction were observed between in-person and telehealth visits of either type or when patients were stratified by age (p = 0.78), gender (p = 0.41), insurance payer group (p = 0.099) or postoperative status (p = 0.19). CONCLUSIONS: Similar rates of satisfaction were observed with both in-person visits and telehealth hand therapy visits. Questions that related to registration and scheduling tended to score lower across all groups, while questions related to technology scored lower in the telehealth groups. Future studies are needed to explore the efficacy and viability of a telehealth platform for hand therapy services.

The Role of Non-animal Origin Feed Ingredients in Transmission of Viral Pathogens of Swine: A Review of Scientific Literature.

The emergence of porcine epidemic diarrhea (PED) in commercial swine in North America and growing concerns about the potential for the introduction of African swine fever (ASF) from China, the European Union, or other affected regions has put a spotlight on the possible role of contaminated feed and feed ingredients in the introduction and transmission of viral swine pathogens. This paper systematically reviews the scientific literature regarding whether non-animal origin ingredients of commercial swine feed could introduce or transmit viral pathogens of swine into or within the United States. The purpose of this review is to identify, evaluate, and summarize the relevant scientific knowledge, published through March 2018, and to identify information gaps and research needs, thereby making the available evidence more accessible to policy makers, the swine industry, and the scientific community. A total of 26 documents were selected for the final review process, which included experimental studies, case reports, epidemiological investigations, and scientific opinion, among others. The review found that the scientific literature has addressed some critical experimental questions pertaining to transmission of swine viruses via feed and feed ingredients, but the current body of scientific knowledge lacks conclusive evidence of virus contamination of non-animal origin feed ingredients of commercial swine feed, particularly for imported commodities, and further investigation into the epidemiology of virus transmission via feed to swine under field conditions through natural feeding behavior is warranted. Additional studies of how imported ingredients of commercial swine feed are sourced, processed, transported and, thus, contaminated prior to importation into the United States are needed. Moving forward, studies designed to examine the likely source(s) of contamination and subsequent virus mitigation steps in processing and post-processing may be the most fruitful focus of research.

A pharmacological master key mechanism that unlocks the selectivity filter gate in K+ channels.

Potassium (K+) channels have been evolutionarily tuned for activation by diverse biological stimuli, and pharmacological activation is thought to target these specific gating mechanisms. Here we report a class of negatively charged activators (NCAs) that bypass the specific mechanisms but act as master keys to open K+ channels gated at their selectivity filter (SF), including many two-pore domain K+ (K2P) channels, voltage-gated hERG (human ether-à-go-go-related gene) channels and calcium (Ca2+)-activated big-conductance potassium (BK)-type channels. Functional analysis, x-ray crystallography, and molecular dynamics simulations revealed that the NCAs bind to similar sites below the SF, increase pore and SF K+ occupancy, and open the filter gate. These results uncover an unrecognized polypharmacology among K+ channel activators and highlight a filter gating machinery that is conserved across different families of K+ channels with implications for rational drug design.

Compatibility between dental adhesive systems and dual-polymerizing composite resins.

STATEMENT OF PROBLEM: Information is lacking about incompatibilities between certain types of adhesive systems and dual-polymerizing composite resins, and universal adhesives have yet to be tested with these resins. PURPOSE: The purpose of this in vitro study was to investigate the bonding outcome of dual-polymerizing foundation composite resins by using different categories of adhesive solutions and to determine whether incompatibilities were present. MATERIAL AND METHODS: One hundred and eighty caries-free, extracted third molar teeth were allocated to 9 groups (n=20), in which 3 different bonding agents (Single Bond Plus [SB]), Scotchbond Multi-purpose [MP], and Scotchbond Universal [SU]) were used to bond 3 different composite resins (CompCore AF [CC], Core Paste XP [CP], and Filtek Supreme Ultra [FS]). After restorations had been fabricated using an Ultradent device, the specimens were stored in water at 37°C for 24 hours. The specimens were tested under shear force at a rate of 0.5 mm/min. The data were analyzed with Kruskal-Wallis tests and post hoc pairwise comparisons (α=.05). RESULTS: All 3 composite resins produced comparable shear bond strengths when used with MP (P=.076). However, when either SB or SU was used, the light-polymerized composite resin (FS) and 1 dual-polymerized foundation composite resin (CC) bonded significantly better than the other dual-polymerized foundation composite resin (CP) (P<.005). Both FS and CC performed best with SU but had acceptable results with all of the bonding agents. CP only performed acceptably with MP (P=.023) and had poor results with both other agents. CONCLUSIONS: Dual-polymerizing composite resins can obtain equally good bond strengths as light-polymerizing alternatives. However, not all dual-polymerizing composite resins perform well with all bonding systems; some incompatibilities exist between different products.

K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac.

TREK-2 (KCNK10/K2P10), a two-pore domain potassium (K2P) channel, is gated by multiple stimuli such as stretch, fatty acids, and pH and by several drugs. However, the mechanisms that control channel gating are unclear. Here we present crystal structures of the human TREK-2 channel (up to 3.4 angstrom resolution) in two conformations and in complex with norfluoxetine, the active metabolite of fluoxetine (Prozac) and a state-dependent blocker of TREK channels. Norfluoxetine binds within intramembrane fenestrations found in only one of these two conformations. Channel activation by arachidonic acid and mechanical stretch involves conversion between these states through movement of the pore-lining helices. These results provide an explanation for TREK channel mechanosensitivity, regulation by diverse stimuli, and possible off-target effects of the serotonin reuptake inhibitor Prozac.

Targeted delivery of photosensitizers: efficacy and selectivity issues revealed by multifunctional ORMOSIL nanovectors in cellular systems.

PEGylated and non-PEGylated ORMOSIL nanoparticles prepared by microemulsion condensation of vinyltriethoxy-silane (VTES) were investigated in detail for their micro-structure and ability to deliver photoactive agents. With respect to pure silica nanoparticles, organic modification substantially changes the microstructure and the surface properties. This in turn leads to a modulation of both the photophysical properties of embedded photosensitizers and the interaction of the nanoparticles with biological entities such as serum proteins. The flexibility of the synthetic procedure allows the rapid preparation and screening of multifunctional nanosystems for photodynamic therapy (PDT). Selective targeting of model cancer cells was tested by using folate, an integrin specific RGD peptide and anti-EGFR antibodies. Data suggest the interference of the stealth-conferring layer (PEG) with small targeting agents, but not with bulky antibodies. Moreover, we showed that selective photokilling of tumour cells may be limited even in the case of efficient targeting because of intrinsic transport limitations of active cellular uptake mechanisms or suboptimum localization.

Exome sequencing identifies a spectrum of mutation frequencies in advanced and lethal prostate cancers.

To catalog protein-altering mutations that may drive the development of prostate cancers and their progression to metastatic disease systematically, we performed whole-exome sequencing of 23 prostate cancers derived from 16 different lethal metastatic tumors and three high-grade primary carcinomas. All tumors were propagated in mice as xenografts, designated the LuCaP series, to model phenotypic variation, such as responses to cancer-directed therapeutics. Although corresponding normal tissue was not available for most tumors, we were able to take advantage of increasingly deep catalogs of human genetic variation to remove most germline variants. On average, each tumor genome contained ~200 novel nonsynonymous variants, of which the vast majority was specific to individual carcinomas. A subset of genes was recurrently altered across tumors derived from different individuals, including TP53, DLK2, GPC6, and SDF4. Unexpectedly, three prostate cancer genomes exhibited substantially higher mutation frequencies, with 2,000-4,000 novel coding variants per exome. A comparison of castration-resistant and castration-sensitive pairs of tumor lines derived from the same prostate cancer highlights mutations in the Wnt pathway as potentially contributing to the development of castration resistance. Collectively, our results indicate that point mutations arising in coding regions of advanced prostate cancers are common but, with notable exceptions, very few genes are mutated in a substantial fraction of tumors. We also report a previously undescribed subtype of prostate cancers exhibiting "hypermutated" genomes, with potential implications for resistance to cancer therapeutics. Our results also suggest that increasingly deep catalogs of human germline variation may challenge the necessity of sequencing matched tumor-normal pairs.

Differentiation and fiber type-specific activity of a muscle creatine kinase intronic enhancer.

BACKGROUND: Hundreds of genes, including muscle creatine kinase (MCK), are differentially expressed in fast- and slow-twitch muscle fibers, but the fiber type-specific regulatory mechanisms are not well understood. RESULTS: Modulatory region 1 (MR1) is a 1-kb regulatory region within MCK intron 1 that is highly active in terminally differentiating skeletal myocytes in vitro. A MCK small intronic enhancer (MCK-SIE) containing a paired E-box/myocyte enhancer factor 2 (MEF2) regulatory motif resides within MR1. The SIE's transcriptional activity equals that of the extensively characterized 206-bp MCK 5'-enhancer, but the MCK-SIE is flanked by regions that can repress its activity via the individual and combined effects of about 15 different but highly conserved 9- to 24-bp sequences. ChIP and ChIP-Seq analyses indicate that the SIE and the MCK 5'-enhancer are occupied by MyoD, myogenin and MEF2. Many other E-boxes located within or immediately adjacent to intron 1 are not occupied by MyoD or myogenin. Transgenic analysis of a 6.5-kb MCK genomic fragment containing the 5'-enhancer and proximal promoter plus the 3.2-kb intron 1, with and without MR1, indicates that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers (types I and IIa, respectively), but is not required for expression in fast-twitch muscle fibers (types IIb and IId). CONCLUSIONS: In this study, we discovered that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers and that MR1's positive transcriptional activity depends on a paired E-box MEF2 site motif within a SIE. This is the first study to delineate the DNA controls for MCK expression in different skeletal muscle fiber types.

Trans genomic capture and sequencing of primate exomes reveals new targets of positive selection.

Comparison of protein-coding DNA sequences from diverse primates can provide insight into these species' evolutionary history and uncover the molecular basis for their phenotypic differences. Currently, the number of available primate reference genomes limits these genome-wide comparisons. Here we use targeted capture methods designed for human to sequence the protein-coding regions, or exomes, of four non-human primate species (three Old World monkeys and one New World monkey). Despite average sequence divergence of up to 4% from the human sequence probes, we are able to capture ~96% of coding sequences. Using a combination of mapping and assembly techniques, we generated high-quality full-length coding sequences for each species. Both the number of nucleotide differences and the distribution of insertion and deletion (indel) lengths indicate that the quality of the assembled sequences is very high and exceeds that of most reference genomes. Using this expanded set of primate coding sequences, we performed a genome-wide scan for genes experiencing positive selection and identified a novel class of adaptively evolving genes involved in the conversion of epithelial cells in skin, hair, and nails to keratin. Interestingly, the genes we identify under positive selection also exhibit significantly increased allele frequency differences among human populations, suggesting that they play a role in both recent and long-term adaptation. We also identify several genes that have been lost on specific primate lineages, which illustrate the broad utility of this data set for other evolutionary analyses. These results demonstrate the power of second-generation sequencing in comparative genomics and greatly expand the repertoire of available primate coding sequences.

Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.

Evidence for the etiology of autism spectrum disorders (ASDs) has consistently pointed to a strong genetic component complicated by substantial locus heterogeneity. We sequenced the exomes of 20 individuals with sporadic ASD (cases) and their parents, reasoning that these families would be enriched for de novo mutations of major effect. We identified 21 de novo mutations, 11 of which were protein altering. Protein-altering mutations were significantly enriched for changes at highly conserved residues. We identified potentially causative de novo events in 4 out of 20 probands, particularly among more severely affected individuals, in FOXP1, GRIN2B, SCN1A and LAMC3. In the FOXP1 mutation carrier, we also observed a rare inherited CNTNAP2 missense variant, and we provide functional support for a multi-hit model for disease risk. Our results show that trio-based exome sequencing is a powerful approach for identifying new candidate genes for ASDs and suggest that de novo mutations may contribute substantially to the genetic etiology of ASDs.

Haplotype-resolved genome sequencing of a Gujarati Indian individual.

Haplotype information is essential to the complete description and interpretation of genomes, genetic diversity and genetic ancestry. Although individual human genome sequencing is increasingly routine, nearly all such genomes are unresolved with respect to haplotype. Here we combine the throughput of massively parallel sequencing with the contiguity information provided by large-insert cloning to experimentally determine the haplotype-resolved genome of a South Asian individual. A single fosmid library was split into a modest number of pools, each providing ∼3% physical coverage of the diploid genome. Sequencing of each pool yielded reads overwhelmingly derived from only one homologous chromosome at any given location. These data were combined with whole-genome shotgun sequence to directly phase 94% of ascertained heterozygous single nucleotide polymorphisms (SNPs) into long haplotype blocks (N50 of 386 kilobases (kbp)). This method also facilitates the analysis of structural variation, for example, to anchor novel insertions to specific locations and haplotypes.

Rapid, low-input, low-bias construction of shotgun fragment libraries by high-density in vitro transposition.

We characterize and extend a highly efficient method for constructing shotgun fragment libraries in which transposase catalyzes in vitro DNA fragmentation and adaptor incorporation simultaneously. We apply this method to sequencing a human genome and find that coverage biases are comparable to those of conventional protocols. We also extend its capabilities by developing protocols for sub-nanogram library construction, exome capture from 50 ng of input DNA, PCR-free and colony PCR library construction, and 96-plex sample indexing.