The COVID-19 viral pandemic has taken the world by surprise. The pandemic has caused a great impact on the mental health and wellbeing of pregnant women with mental health difficulties. Healthcare providers veered towards video-telemedicine to safely and swiftly provide services to its users.To determine impact of Video-telemedicine on: 1. Access to Care 2. Ease of Use 3. Quality of Care 4. Difficulties of Use 5. Future Prospects of Video TelemedicineWe have decided to conduct a targeted survey to 100 pregnant women who are known to Perinatal Mental Health services to assess the new methods of contact that the viral pandemic has enforced upon healthcare providers.Pre-pandemic: video-telemedicine was ranked as least preferred Post-pandemic it is ranked as second favourite. 70.4% of responders have confirmed that video-telemedicine significantly facilitated access to care. 23.3% of responders insisted video-telemedicine made the service better. 50% of responders thought it was much easier to use video options to access their care services needs 95.4% of responders felt that video-telemedicine alternatives should remain post-pandemicVideo-telemedicine options have significantly improved the access and quality of services provided by Community Health Services to pregnant women during the pandemic. Video options can also make it easier to reach critical care without negatively affecting the quality of wholistic care provided, in fact, it can sometimes improve it. It is important that the psychiatric field learn from this pandemic and implement these services permanently. Bigger and wider studies need to be done in the future to support these conclusions.No significant relationships.


Mycobacterium shottsii is a dysgonic, nonpigmented mycobacterium originally isolated from diseased striped bass (Morone saxatilis) in the Chesapeake Bay, USA. Genomic analysis reveals that M. shottsii is a Mycobacterium ulcerans/Mycobacterium marinum clade (MuMC) member, but unlike the superficially similar M. pseudoshottsii, also isolated from striped bass, it is not an M. ulcerans ecovar, instead belonging to a transitional group of strains basal to proposed “Aronson” and “M” lineages. Although phylogenetically distinct from the human pathogen M. ulcerans, the M. shottsii genome shows parallel but nonhomologous genomic degeneration, including massive accumulation of pseudogenes accompanied by proliferation of unique insertion sequences , large-scale deletions, and genomic reorganization relative to typical M. marinum strains. Coupled with its observed ecological characteristics and loss of chromogenicity, the genomic structure of M. shottsii is suggestive of evolution toward a state of obligate pathogenicity, as observed for other Mycobacterium spp., including M. ulcerans, M. tuberculosis, and M. leprae.IMPORTANCEMorone saxatilis (striped bass) is an ecologically and economically important finfish species on the United States east coast. Mycobacterium shottsii and Mycobacterium pseudoshottsii were originally described in the early 2000s as novel species from outbreaks of visceral and dermal mycobacteriosis in this species. Biochemical and genetic characterization place these species within the Mycobacterium ulcerans/M. marinum clade (MuMC), and M. pseudoshottsii has been proposed as an ecovar of M. ulcerans. Here, we describe the complete genome of M. shottsii, demonstrating that it is clearly not an M. ulcerans ecovar; however, it has undergone parallel genomic modification suggestive of a transition to obligate pathogenicity. As in M. ulcerans, the M. shottsii genome demonstrates widespread pseudogene formation driven by proliferation of insertion sequences, as well as genomic reorganization. This work clarifies the phylogenetic position of M. shottsii relative to other MuMC members and provides insight into processes shaping its genomic structure. Morone saxatilis) with ulcerative dermal granulomatous inflammation and visceral granulomatous disease emerged in 1997 and were of concern because of the high economic and ecological value of this finfish  mycobacterium with rough, nonpigmented colonies and little to no growth above 30°C. Biochemically, M. shottsii is negative for arylsulfatase, variable for catalase, negative for pyrazinamidase and Tween hydrolysis, and positive for urease. Both M. shottsii and the related M. pseudoshottsii can be differentiated from Mycobacterium marinum by positive niacin production  but reduced virulence relative to that of M. marinum   , 9.M. shottsii to grow above 30°C combined with its relatedness to the etiological agent of tuberculosis has piqued interest in its possible use as a mammalian intranasal vaccine vector  but was not discussed in the pertinent article (AP022572 with the genome presented in this work (CP014860) indicates syntenic assemblies of similar size .The genome of of 65.5% . No plasMysh01 was by a large margin the most common insertion sequence in M. shottsii and appears unique to this bacterium among the M. ulcerans/M. marinum complex (MuMC). The closest BLAST match for the single transposase coding sequence (CDS) in this IS was to a Mycobacterium thermoresistibile transposase, at 79.9%. Inverted repeats for ISMysh01and the M. thermoresistibile transposase were identical, and both showed structure typical for IS5/IS5 family/group IS elements, including a single open reading frame (ORF), inverted terminal repeats, and 4-base direct repeats (CTAG) (Mysh01 has lower similarity (68.3%) to single-copy transposases from M. marinum strains CCUG 20998 and ATCC 927 and M. tuberculosis group bacteria (ISMt1-family). These IS are annotated with two transposase CDS, consistent with the IS427 group of the IS5 family. An additional marginally similar IS5/IS427 transposase is low-multicopy in Rhodococcus opacus (CP009111) and single-copy in Arthrobacter sp. (CP040018), suggesting widespread distribution of this IS type among the Actinomycetales. The second-highest copy-number insertion sequence ISMysh03 was also unique to M. shottsii among the MuMC group, with the closest BLAST matches being to an integrase pseudogene in M. chimaera (86.5%. identity) and to an Rv3128c-like protein in Mycobacterium celatum plasmid pCLP (AF312688) (84.4% identity). Family classification of ISMysh03 was not possible. ISMysh04 and 05 were highly similar (≥99%) to insertion sequences ISMyma01 and 05, respectively, from M. marinum M. Both of these elements are widespread in MuMC genomes  element is present, but additional copies of the first (15 copies) and second (17 copies) CDS are present at multiple sites in the genome. ISMysh06 and ISMysh07, both present in 4 copies in the M. shottsii genome, are present in other Aronson lineage (Insertion sequences (IS) were prevalent in the chromosome , includis (CTAG) . ISMysh0 genomes . ISMysh0 lineage  strains,M. marinum M and M. ulcerans group organisms and the clearly distinct cluster II “Aronson lineage” containing M. marinum ATCC 927 and the laboratory strain 1218R  were highly similar, with 93 single-nucleotide polymorphisms (SNPs) separating the most distantly related strains. M. shottsii M175 belonged to a cluster of nearly clonal strains differing among each other by no more than 19 SNPs . This number is intermediate between 771 pseudogenes predicted for M. ulcerans Agy99 and 436 for M. ulcerans ecovar Liflandii (M. shottsii (199/590) are also annotated as pseudogenes in M. ulcerans. A substantial number of pseudogenes were created by disruption with insertion sequences (38.8%). Large internal deletions accounted for less than 1% of pseudogenes. Chi-square analysis of the frequency of pseudogenes belonging to different functional categories versus functional (complete) CDS in the M. shottsii genome demonstrated a significant difference . Examination of residuals from the analysis indicated that secondary metabolite biosynthesis, transport, and catabolism genes (Q) were disproportionately well represented in the pseudogene set, as were ESX-type loci  to the analysis reduced the core protein set to 2,885, and M. shottsii retained 261 unique proteins  and phiMS_3 (TM48_03961 to 03972). An additional 8 unique CDS in a region (TM48_04661 to TM48_04680) immediately downstream of phiMS_2 also had various degrees of significant BLAST similarity to prophages in other organisms. Additional regions resembling prophage sequences (TM48_1160-TM48_1162 and TM48_1426-TM48_1449) contained 16 CDS unique to M. shottsii. Of M. shottsii-specific proteins, 121 were annotated as hypothetical proteins, 82 as transposases, and 37 as proline-glutamate (PE)/proline-proline-glutamate (PPE) proteins. A list of proteins representative of each Venn region presented in M. shottsii does not appear to have acquired significant amounts of genetic material from outside sources, and its phenotypic differences from other M. marinum-group organisms appear to stem largely from genomic degeneration and pseudogene accumulation.Ortholog analysis among  ecovars  indicateproteins . M. ulceM. marinum M were determined among M. ulcerans, M. shottsii, and M. marinum ATCC 927. Thirty-one RDs (16.8%) were present in all three species, including all 10 annotated prophages in M. marinum M and all 4 copies of the ISMyma04 insertion sequence. Also included were 2 metabolic loci (M. ulcerans regions of deletion [MURDs] 2 and 73), 4 PPE/PGRS loci , and 2 regions containing nonribosomal peptide synthase loci (MURDs 2 and 105). Other shared RDs were of unknown function. The majority  of RDs were unique to M. ulcerans, and few RDs were conserved between M. ulcerans and M. marinum ATCC 927, including both copies of ISMyma05 and a large intermediary metabolism locus that was partially deleted in M. marinum ATCC 972. A larger number of RDs  were present in both M. ulcerans and M. shottsii; however, these RDs included 7 repeat regions and two copies of ISMyma06. Further, few of these RDs demonstrated high reciprocal coverage, with most being small partial deletions contained within a larger deleted region in the opposite species. Twenty-six (14.1%) RDs were unique to M. shottsii (Table S2), and 4 (2.1%) were unique to M. marinum ATCC 927. An additional eight RDs (4.3%) were shared between M. shottsii and M. marinum ATCC 927 (Table S2). Regions of deletion unique to M. shottsii (MSRD) comprised 163 CDS, and the majority (20/26) were flanked by insertion sequences, especially ISMysh03, which was present at half (10/20) of the RD boundaries, despite representing only 27% of insertion sequence copies in the genome. A variety of secondary metabolism loci were represented in M. shottsii-specific RDs, including glycosyltransferases and acyl-coenzyme A (coA) dehydrogenase. Three of four copies of acetolactate synthase ilvB present in M. marinum M are either pseudogenes or deleted in M. shottsii. Acetolactate synthase generates acetolactate from pyruvate and is the first step in the synthesis of the branched-chain amino acids (BCAA) , as is one copy encoding PpiC peptidyl-prolyl cis-trans isomerase (MSRD27). Peptidyl-prolyl isomerases (cyclophilins) are protein chaperones secreted by M. tuberculosis during intracellular infection and may contribute to virulence by mimicking host cyclophilins (mce) operons are virulence factors in M. tuberculosis  is deleted for the associated YrbE transporter permeases  loci relative to s (BCAA) . While prculosis  but may majority /26 were ermeases .Mycobacterium shottsii possesses requisite pathways for aerobic respiration, including intact glycolysis and pentose phosphate pathways. Glyoxylate shunt enzymes isocitrate lyase and malate synthase are intact, and therefore M. shottsii, like other members of the MuMC, should be able to utilize 2-carbon compounds for synthesis of carbohydrates. A complete tricarboxylic acid (TCA) cycle is present. Beta-oxidation pathways are predicted to be present and functional, and like M. marinum M, a high level of gene duplication is observed at most levels of the pathway. Forty FadD (acyl-CoA synthase) paralogs are predicted, as are 25 EchA (enoyl-coA oxidase) and 12 FadA (3-ketoacyl-CoA thiolase) paralogs. The alternate anaerobic respiratory pathway genes annotated as nitrate reductase and formate dehydrogenase in M. marinum M  and phenolic glycolipids (PGL) , as it is in M. ulcerans Agy99. The gene disruptions to this locus in M. shottsii and M. ulcerans differ in location, and an IS5-family transposase is present in M. shottsii. Other PKS loci described in M. marinum M  are not present in either M. shottsii or M. ulcerans. The phytoene dehydrogenase crtI, one of five genes involved in biosynthesis of the carotenoid pigment isorenieratene, responsible for orange pigmentation in chromogenic mycobacteria (M. shottsii as it is in M. ulcerans and is likely responsible at least in part for the nonpigmented phenotype of M. shottsii.All requisite CDS for type I and type II fatty acid synthase pathways are intact in ds (PGL) , 25. The marinum . Other prculosis , is potebacteria , is a psM. shottsii, representing a total of 7.3% of coding capacity. The number of PE/PPE proteins in M. shottsii is intermediate to that in M. marinum M  and M. ulcerans Agy99 . PE/PPE proteins are hypothesized to have proliferated among M. tuberculosis and related species, including the MuMC  family proteins and other proteins from mycobacteria. Pathogenic mycobacteria encode as many as five type VII secretion systems, ESX-1 to ESX-5; ESX-1, ESX-3, and ESX-5 are essential for bacterial viability or virulence  is the primary attenuator of the strain (M. marinum M contains 29 esx genes in at least 5 loci (ESX 1 to 5) (M. marinum (ESX-6), resulting in nearly identical copies of esxA and esxB secretion system genes. M. shottsii has one copy of esxA and esxB loci (TM48_00416 to TM48_00417). Relative to M. marinum M, the ESX-1 locus of M. shottsii (TM48_00412 to TM48_00427) is disrupted downstream of eccD1 (MMAR_RS27385) by several insertions of ISMysh01 and ISMysh02 and appears to have undergone genomic reorganization with the remainder of the locus (espK-mycP1) found at TM48_05472 to TM48_05476. At least one hypothetical protein (MMAR_RS27390) has been disrupted by frameshift in this region. This reorganization is not present in M. marinum ATCC 927 or M. ulcerans, and its effect on ESX-1 function in M. shottsii remains to be resolved.ESX loci encode type VII secretory systems necessary for secretion of the irulence –32. ESX-rophages . Deletioe strain . The gen 1 to 5) . ESX-1 iM. shottsii ESX-2 has a complete eccA2 locus, unlike M. marinum M; however, esxC and esxD loci are absent as they are in M. marinum M, M. ulcerans, and M. ulcerans ecovar Liflandii. Examination of other available M. marinum genomes, however, reveals that complete ESX-2 operons such as those found in M. tuberculosis are present in several strains , and a partial operon flanked by ISMysh01 repeats is present in M. shottsii  and fast-growing (such as Mycobacterium smegmatis) mycobacteria (eccB gene in ESX-4 is a pseudogene in M. shottsii (TM48_02015), disrupted by ISMysh01.The bacteria , 37. ESXbacteria , 38. Desbacteria , the eccMycobacterium marinum-related pathogens Mycobacterium shottsii and Mycobacterium pseudoshottsii were described around the same time (early 2000s) from the same fish species  and are closely similar at major gene loci used for multilocus sequence typing (MLST), as expected for members of the MuMC. Further genomic-level work was performed on M. pseudoshottsii, demonstrating it to be part of the M. ulcerans clade, and it underwent genomic modifications similar to those of M. ulcerans, including acquisition of the pMUM megaplasmid and highly multicopy insertion sequence IS2404  supplemented with 10% albumin-dextrose-sodium chloride (ADS) . Mycobacterium marinum ATCC 927 was obtained from the American Type Culture Collection and grown in Middlebrook 7H9 broth supplemented with oleic acid/albumin/dextrose/catalase (OADC) and 0.05% Tween 80 at 25°C with gentle shaking.de (ADS) , 0.5% glM. shottsii cells were grown in 7H9 ADS plus 0.5% glycerol plus 0.25% Tween 80 at 25°C to an optical density at 600 nm (OD600) of 0.8 to 1.0, treated with cycloserine (1 mg/mL) and carbenicillin (0.1 mg/mL), and then incubated 3 additional days. Cells were harvested by centrifugation  at room temperature, washed with spheroplasting buffer , and suspended in 1 mL of the same buffer. Bacteria were counted using a Petroff-Hausser chamber, and suspensions of 2 × 109 and 4 × 109 cells/mL were prepared by dilution with spheroplasting buffer. Aliquots of 0.5 mL were then mixed with an equal volume of molten (55°C) 1.5% SeaPlaque GTG agarose , dissolved in 50 mM EDTA, and then pipetted into 50-well disposable plug molds  and incubated 90 min at 4°C.Plugs of agarose-embedded bacterial cells were incubated in lysis buffer 1  at 37°C for 24 h and then incubated in lysis buffer 2 (proteinase K [1 mg/mL] dissolved in 0.5 M EDTA [pH 9.0 to 9.5] and 1% N-lauroyl sarcosine) at 50°C for 48 h. The plugs were washed five times with TE buffer by gentle inversion to remove detergent residue and shipped in Tris-EDTA (TE) buffer to Opgen . Genome mapping of restriction endonuclease NheI sites was performed at Opgen using previously described methodology .M. shottsii M175 was cultured as described above in 50 mL of medium and harvested by centrifugation . Cells were washed with TE buffer and extracted with chloroform methanol (2:1), and phases were separated by centrifugation . The cells were recovered and suspended in 1 mL disruption buffer  with medium vortexing for 1 min, and cell debris was sedimented by centrifugation . Supernatant was wadded to a 2 mL heavy phase-lock gel tube  and extracted with an equal volume of phenol-chloroform/isoamyl alcohol (25:24:1) by inversion. Phases were separated by centrifugation . The aqueous phase was extracted a second time with phenol-chloroform/isoamyl alcohol (25:24:1), and particulates were removed by centrifugation . The DNA was precipitated with 0.3 M sodium acetate (pH 5.2) and an equal volume isopropanol, pelleted by centrifugation , washed with cold 70% ethanol, dried by evaporation, dissolved in nuclease-free water over several days, and treated with DNase-free RNase A. Mycobacterium shottsii M175 DNA was sequenced using MiSeq PE250 platform at the University of Georgia Genomics Center. Other M. shottsii strains and M. marinum ATCC 927 were extracted using the DNeasy extraction kit  preceded by beadmilling with 0.1-mm Si-Zi beads for 40 s at 5,000 rpm. DNA quantity and quality were determined using NanoDrop. M. shottsii strains were sequenced with Illumina PE250 chemistry at the UT Austin Genomic Sequencing and Analysis Facility to a depth of at least 50×. Sequencing using the PacBio Sequel system was performed at the Centers for Disease Control and Prevention (M. shottsii M175) and Washington State University (M. marinum ATCC 927). PacBio sequencing of M. shottsii M175 using 3 single-molecule real-time (SMRT) cells (10 kb prep) resulted in 499,283 reads, total read length of 1,058,725,898 bases, mean read length of 2,120 bases, and 153× genome coverage. After assembly with HGAP3, 14 contigs resulted, and 13 were spurious (<20× coverage). After sequences were trimmed and requivered, a genome of 5,956,408 bp was obtained. The genome was polished with Pilon (v1.23) under defaults using Illumina reads, and a final genome size of 5,956,421 bp was obtained. PacBio sequencing of M. marinum ATCC 927 resulted in 137,098 reads, total read length of 1,210,762,761 bp, and ~144× coverage of two contigs of the chromosome  and a plasmid . This assembly of M. marinum ATCC 927 was used for analyses described in this work that occurred before the completed ATCC 927 genome was made available by a separate group (NZ_AP018496) . M. shottsii M175 and M. marinum ATCC 927 genomes were annotated using Prokka (M. marinum and M. ulcerans ecovar genomes as well as neighboring BLASTP searches (https://www.ncbi.nlm.nih.gov/genomes/frameshifts/frameshifts.cgi). For purposes of comparative analyses, genomes were reannotated with Prokka from original .fasta files.Celera whole-genome sequencing (WGS)  was usedg Prokka  with mang Prokka . PseudogM. marinum M or M. marinum ATCC 927 is reported. Ortholog analysis was performed with ProteinOrtho (v. 6.0.30) using default settings, -singles option to identify unique proteins and the -blastself option to collapse multicopy CDS (M. ulcerans Agy99. Venn diagrams were produced in Rstudio (R version 4.1.1) with the VennDiagram package. Prophages were identified using PHASTER (PHAge Search Tool—Enhanced Release) (M. marinum prophage. Deletion regions of difference (RDs) were detected in M. shottsii or M. marinum ATCC 927 relative to reference genome M. marinum M (Table S2). A custom Perl script (https://github.com/DGauthierLab/misc_scripts) was used to detect RDs of ≥750 bp in length with <5× coverage. RDs from M. shottsii and M. marinum were compared for sequence conservation with M. ulcerans regions of difference (MURDs) and to the M. marinum M genome. Regions with <50% overlap were considered unique to a particular organism. In some cases, multiple RDs from an organism were contained within a larger RD from another; in these cases, the larger locus was characterized, and the smaller RD was subsumed within.Core and total genomic single-nucleotide polymorphism (SNP) alignments were generated using kSNP v.3.021 . Phylogecopy CDS . Publiclcopy CDS , with thRelease) . The lisM. shottsii M175 genome sequence is available from NCBI GenBank, accession number CP014860. The complete M. marinum ATCC 927 genome was recently made available (NZ_AP018496) and is syntenic and consistent with the ATCC 927 sequence produced in this work. Sequence reads for M. shottsii strains other than M175 are available from the NCBI Sequence Read Archive (PRJNA816683).The complete vailable  (GenBank


Auricular Arteriovenous Malformation of the external ear is a rarely encountered disease; in particular, arteriovenous malformation arising from the auricle, with spontaneous bleeding, has seldom been reported.In the current study, we report an unusual case of late-onset auricular arteriovenous malformation originating from the posterior auricular artery that was confirmed by computed tomographic angiography. The case was successfully managed by pre-surgical intravascular embolization followed by total lesion excision. Prompted by this case, we also present a scoping review of the literature.A case of a 60 year-old man with right auricular arteriovenous malformation treated in our tertiary care center, and 52 patients with auricular arteriovenous malformation described in 10 case reports and a retrospective review are presented. Auricular arteriovenous malformation can manifest as swelling of the ear, pulsatile tinnitus, pain, and/or bleeding. On physical examination, a pulsatile swelling and/or a tender mass is evident. When arteriovenous malformation is suspected, the lesions should be visualized using imaging modalities that optimally detect vascular lesions, and managed via embolization, mass excision, or auricular resection. Effectiveness of the various diagnostic methods used and the treatment outcomes were analyzed.Various imaging modalities including Doppler sonography, computed tomographic angiography, magnetic resonance angiography, and/or transfemoral cerebral angiography were used to diagnose 38 cases reported in the literature. In another 15 cases, no imaging was performed; treatment was determined solely by physical examination and auscultation. Of the total of 53 cases, 12 were not treated (their symptoms were merely observed) whereas 20 underwent therapeutic embolization. In total, 32 patients, including 1 patient who was not treated and 10 with persistent or aggravated arteriovenous malformation after previous embolization, underwent mass excision or auricular resection depending on the extent of the lesion. No major postoperative complication was recorded. The postoperative follow-up duration varied from 1 month to 19 years, and only one case of unresectable, residual cervicofacial arteriovenous malformation was recorded.Auricular arteriovenous malformation is a rarely encountered disease, but should be suspected if a patient presents with a swollen ear and pulsatile tinnitus. Appropriate imaging is essential for diagnosis and evaluation of the extent of disease. As embolization affords only relatively poor control, total surgical removal of the vascular mass is recommended. An Arteriovenous Malformation (AVM) is an abnormal connection between one or more arteries and veins, bypassing the capillary system.Here, we report an unusual case of late-onset auricular AVM originating from the posterior auricular artery. Also, a scoping review of the literature allows us to discuss the roles played by imaging in the diagnosis and management of AVM.http://www.ncbi.nlm.nih.gov/pubmed/) searches to identify all studies on AVM of the external ear.We adhered to the PRISMA  guideline when performing PubMed . The literature review identified a total of 52 AVM patients described in 11 reports (10 case reports and 1 retrospective review). The 10 case reports dealt with 11 cases of auricular AVM and the single review analyzed 41 cases. The chief complaints, duration of symptoms, events that aggravated the AVMs, and history of spontaneous AVM bleeding were analyzed.The laterality, location, and extent of AVM were investigated. Various diagnostic imaging modalities including Doppler Sonography (DS), Temporal Bone Computed Tomographic Angiography (TBCTA), Magnetic Resonance Angiography (MRA), and/or Transfemoral Cerebral Angiography (TFCA) were employed in individual cases, and the findings of the key diagnostic modalities were reviewed. In patients who underwent diagnostic angiography, the main arteries and feeder vessels are summarized.The AVM management options included observation, embolization, mass excision, or auricular resection. After the treatment, the clinical condition was described as controlled, improved, persistent, or aggravated. We also explored the application of reconstructive procedures such as Skin-Thickness Split Grafting (STSG) and total auricular reconstruction. Postoperative complications, follow-up durations, and final status were reviewed.A 60 year-old man visited the emergency department with massive spontaneous bleeding from the right ear. He had a history of recurrent swelling of the right auricle, and pulsatile tinnitus. Three years prior, the patient had visited our outpatient clinic with recurrent auricular swelling, and was diagnosed with an otohematoma because of the cauliflower-like appearance of the auricle.On physical examination, the right auricle exhibited excessive swelling and discoloration A. The tyUnder local anesthesia, the skin was incised along the vertical plane of the right auricle and the AVM mass was totally excised B. The adThe flow chart of n = 18); STSG (n = 10); immediate reconstruction using salvaged auricular cartilaginous framework covered by temporoparietal flap (n = 1), expanded local flap (n = 1), advancement flap (n = 1), and free flap (n = 1). One patient underwent a two-staged operation: auricular resection and STSG initially and ear lobule creation and ear elevation secondarily.A total of 21 patients underwent AVM mass excision or auricular resection as initial treatment. Of these patients, plus a further 11 who underwent excision or resection as salvage management, 22 (69%) were controlled and 9 (28%) improved, and only one had a persistent unresectable AVM in the adjacent region. In these 32 patients, wound closure was performed by simple linear closure (Schobinger classified AVM into four stages. The symptoms of stage I (quiescence) are warm and discolored skin; those of stage II (expansion) are bruit, pulsation, and swelling. Stage III (destruction) is characterized by pain, ulceration, and bleeding; whereas stage IV (decompensation) features cardiac failure.Enlargement of an AVM may be triggered by trauma, infection, or hormonal influences.In two case reports, surgical intervention was planned under suspicion of AVM in the absence of imaging data.Treatment is unnecessary  if the AVM is small and asymptomatic. In an untreated group of 12 patients, 2 of stage I and 7 of stage II remained stable.Our case was initially misdiagnosed as an otohematoma because of the cauliflower-like auricle, and the patient presented 3 years later with massive bleeding. To accurately diagnose an AVM, meticulous physical examination including palpation and auscultation and imaging are essential. In most cases of auricular AVM, optimal treatment is a combination of super-selective embolization and complete surgical excision.10.13039/501100004726Ministry of Health & Welfare, Republic of Korea (grant number HI14C2264).This work was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the The authors declare no conflicts of interest.


WNT10A and WNT10B, which are considered to be genes of the same origin, have been identified as causative genes for tooth deficiency in humans. However, the disrupted mutant of each gene does not show a decrease in teeth number. A negative feedback loop, interacting with several ligands based on a reaction–diffusion mechanism, was proposed to be important for the spatial patterning of tooth formation, and WNT ligands have been considered to play a pivotal role in controlling tooth patterning from mutant phenotypes of LDL receptor-related proteins (LRPs) and WNT co-receptors. The Wnt10a and Wnt10b double-mutants demonstrated severe root or enamel hypoplasia. In −/−Wnt10a and +/−;Wnt10b−/−Wnt10a mice, changes in the feedback loop may collapse the modulation of fusion or split a sequence of tooth formation. However, in the double-knockout mutant, a decrease in the number of teeth was observed, including the upper incisor or third molar in both jaws. These findings suggest that there may be a functional redundancy between Wnt10a and Wnt10b and that the interaction between the two genes functions in conjunction with other ligands to control the spatial patterning and development of teeth.WNT molecules are the regulators of various biological functions, including body axis formation, organ development, and cell proliferation and differentiation. WNTs have been extensively studied as causative genes for an array of diseases.  EDA, MSX1, PAX9, WNT10A, and WNT10B, have been identified as causative for non-syndromic human tooth agenesis [EDA, MSX1, and PAX9 are majorly responsible for premolar, molar, and anterior tooth deficiencies, respectively. However, the characteristics of defect sites in individuals with WNT10A or WNT10B GPVs remain unknown [Several genes, such as agenesis ,3,4,5. G unknown ,7.WNT10A and WNT10B are located at chromosome 2q35 and 12q13.12, respectively. Wnt10a is preferentially expressed in the dental epithelium and enamel knots during tooth development [WNT10A and WNT10B are paralogs with 62% amino acid sequence identity in humans and are speculated to have evolved after ancestral gene duplication that occurred in the evolution of the jawed vertebrate lineage [Msx1-, Pax9-, and Eda-knockout mice, as in the human phenotype. −/−Msx1 mice have palatal clefts and tooth deficiencies [−/−Pax9 mice also have few teeth and a cleft palate [Eda−/− mice exhibit tooth agenesis and dwarf teeth [Wnt10a or Wnt10b mutant mice.WNTs are secretory glycoproteins that play a critical role in the Wnt/β-catenin pathway ,9. The Welopment . WNT10A  lineage . Accordiciencies . Pax9−/−t palate . Eda−/− rf teeth ,18. HoweWnt10 paralogs are expressed at E9.5–E11.5, particularly in limb buds [Wnt10a and other WNT gene expression, as well as Wnt/β-catenin signaling activity, are primarily restricted to the epithelium [Wnt10a is expressed first in the dental placode and later in primary and secondary enamel knots; therefore, Wnt10a potentially functions in tooth initiation and crown patterning. Yamashiro et al. [Wnt10a is expressed in the secretory odontoblasts, lining dentin, and differentiating odontoblasts around Hertwig’s epithelial root sheath during the later stages of tooth development. Therefore, Wnt10a may also potentially function as a key molecule for dentinogenesis during dentin, root, and cusp morphogenesis. Wnt10b is also expressed in the tooth germ [Wnt10b in mice is first detected at E11.5, a stage showing slight thickening of the presumptive epithelium, which is the major feature of early tooth development. Wnt10b is also expressed in the bone marrow, postnatal growth plates [imb buds . In the ithelium , and staithelium . Dassuleithelium  have eluo et al.  demonstroth germ ,23. Exprh plates , and osth plates .WNT10A GPVs are candidate causes for autosomal-dominant selective tooth agenesis; moreover, homozygous or compound heterozygous are responsible for other autosomal recessive ectodermal dysplasia syndromes such as odonto-onycho-dermal dysplasia (OMIM# 257980) [WNT10A. On the other hand, the lateral incisors are reportedly the most frequently missing permanent teeth in patients with WNT10B GPVs [WNT10B GPVs are associated not only with oligodontia and isolated tooth agenesis but also with microdontia, short tooth roots, dental pulp stones, and taurodontism. An in vitro study revealed that mutant Wnt10b ligands failed to efficiently induce endothelial differentiation of dental pulp stem cells [Heterozygous  257980) . However10B GPVs . Moreoveem cells .Wnt10a−/− and −/−Wnt10b mice. However, Wnt10a−/− mice reportedly exhibit abnormal development of ectodermal tissues, such as hair, sweat glands, and taste buds [−/−Wnt10a mice, supernumerary teeth were observed behind the mandibular third molars. Moreover, Wnt10a deficiency causes enamel hypoplasia, leading to roundish teeth, as well as taurodontic root morphology [−/−Wnt10b mice, tooth number and morphogenesis were not evidently delineated, although bone mineral density was reduced [Previous studies have not confirmed a reduced number of teeth in ste buds . In placrphology . In Wnt1 reduced .Wnt10a and Wnt10b are evolutionarily close and show similar expression patterns; therefore, functional redundancy is expected. In this study, various double mutants were generated to verify the functional redundancy of Wnt10a and Wnt10b in tooth development, resulting in various tooth phenotypes. These findings suggested that Wnt10a and Wnt10b may compensate for these mutual functions.All animal experiments were approved by the Ethics Committee of the Tokushima University for Animal Research . All procedures were performed in accordance with the Guidelines for Animal Experiments of the Tokushima University and the ARRIVE guidelines. Both male and female mice were used for morphological tooth observation, and no significant sex differences were noted. Only male mice were used for body length measurement.Wnt10a and Wnt10b were designed as shown in www.idtdna.com/CRISPR-Cas9, accessed on 1 June 2019), in the proprietary Alt-R format. To prepare the RNP complex, two Alt-R crRNAs for each gene were hybridized with Alt-R tracrRNA  and then assembled with recombinant Cas9 protein . The resulting RNP complex was diluted to final concentrations of 200, 400, and 50 ng/mL in Opti-MEM I  for crRNA, tracrRNA, and Cas9 protein, respectively. After preparation, the samples were used for electroporation.Targeted sequences in 2 in an incubator. The resulting two-cell embryos were transferred into the oviducts of pseudo-pregnant MCH/ICR mice on the following day.B6D2F1 (C57BL/6 × DBA2 F1) mice were used to obtain genome-edited F0 mutants in this study. In vitro fertilization (IVF) was performed to obtain fertilized eggs. After a 3 h culture of oocytes and sperm, the eggs were removed from the sperm and cultured for 2 h until electroporation. For preincubation media, mHTF or CARD FERTIUP  was used for each oocyte or sperm. The Genome Editor electroporator and LF501PT1-5 platinum plate electrodes   were used for electroporation. Thirty to forty zygotes, prepared using IVF, were subjected to electroporation at one time. The collected zygotes, cultured in M16 medium, were placed in a line in the electrode gap, filled with 5 μL of Opti-MEM I, containing the RNP complex, and subjected to electroporation. The electroporation conditions were 30 V (3 ms ON +/− 97 ms OFF), for a total of seven times. After electroporation, zygotes were immediately collected from the electrode chamber and cultured in M16 medium at 37 °C and 5% COThe soft tissue of 4-week-old mice was resected and fixed overnight in 95% ethanol/PBS. The skulls were analyzed using high-resolution µCT . Two-dimensional images were used to generate three-dimensional (3D) renderings using the CTVox 3D Creator software . The resolution of the µCT image was 9 μm/pixel.Wnt10a primer pair , and a Wnt10b primer pair (Forward 5′-CTCCTGTTCTTGGCTTTGTTCAGTC-3’ and reverse 5′-CTGTGTGTGCTGCTGCCCAG-3′), according to the manufacturer’s instructions. After verifying the amplicon size, F0 mice were mated with wild-type C57BL/6J mice, and the disrupted alleles were sequenced with a BigDye Terminator Sequence Kit ver. 3.1 and ABI 3500xL Genetic Analyzer  to propagate the alleles of interest. Subsequently, the F2–F4 generations were analyzed.To validate CRISPR/Cas9-mediated mutations, genomic DNA was extracted from the tail biopsies. The genomic regions flanking the guide RNA target were PCR amplified with KOD-Plus-Neo , a p < 0.05; ** means p < 0.01.Each experiment was independently repeated a minimum of three times for each set of conditions. Data are expressed as mean ± standard deviation (SD). Data were analyzed using the Turkey test. * Means Wnt10a and Wnt10b were targeted using the CRISPR/Cas system in mice. The PAM sequence is highlighted in red. The entire Wnt10a coding region was deleted in the Wnt10a-knockout mutant used in a previous study [Wnt10a. Wnt10a was disrupted from the middle region of exon 2 to the middle region of exon 3, and as a result, Wnt10a mutant alleles had 7046-nucleotide deletion  or Wnt10b−/− (n = 5) mutant mice generated in this study showed tooth deficiency  appear behind M3 teeth in the mandible. The M4 tooth was small in size with one cusp , second molar (M2 teeth), and third molar (M3 teeth). None of the ficiency A,B. Althone cusp . These ps report ,28 , two lingual cusps  and three central cusps   Figure A. In theM3 teeth B,C. In tM3 teeth B,C. In c−/− mice A,B. No cobserved B,C.Wnt10a and Wnt10b did not show any differences in craniofacial development or the number and shape of teeth compared with the wild-type mice  differences in body length , distal buccal root (DB root), and palatal root (P root) A,B. In Wt arrow, A. No dif−/− mice A. In Wnt−/− mice A.Wnt10a−/− mouse molars, enlargement of the pulp chamber was observed, resulting in taurodonts. Wnt10a−/−;Wnt10b+/− mice showed more severe taurodontism phenotypes with an apical displacement of the pulp floor and bifurcation of the roots compared to Wnt10a−/− mice. No differences in root morphogenesis were observed between the Wnt10b−/− and Wnt10a+/−;Wnt10a+/− mice and wild-type mice. In Wnt10a+/−;Wnt10b−/− mice, the root morphology of the M1, M2, and M3 teeth were not changed compared to wild-type mice; however, the supernumerary tooth with a single root in diastema appeared  and distal root (D root), and the M3 teeth had a single root. As reported in previous studies , in Wnt1urodonts B.WNT signaling regulates the patterning and differentiation of many tissues and organs in the developing embryo through the temporary and spatial restricted expression of multi-gene families encoding 18 ligands, receptors, pathway modulators, and intracellular components. WNTs include their paralogs in family members . They arWise−/− or Lrp4 mutants [Lrp4 mutants, with Lrp5 or Lrp6 mutants, have recovered normal dentition, suggesting that Lrp5/6 is a Wnt co-receptor competing with Lrp4 for binding to Frizzled receptors. Several scenarios regarding the relationship between Lrp4, Lrp5/6, Wise, and Wnt have been described, and it has been hypothesized that Lrp4 and Wise physically interact to negatively regulate Wnt/β-catenin signaling [Lrp4 leads to the disruption of the normal distribution and/or function of Wise, causing an elevated Wnt/β-catenin signaling at the epithelial signaling center of R2 [Wnt10b−/− mice did not show any phenotypes of tooth number, root, and molar cusp pattern; however, Wnt10a+/−;Wnt10b−/−mice had the supernumerary tooth in diastema, indicating that changes in quantity of Wnt signaling cause survival of R2.In mice, there are one incisor and three molars in each jaw quadrant. A gap between the incisor and the molars is called diastema. The diastema normally lacks the function of tooth formation because Wise suppresses the survival of diastemal buds ,30. Both mutants , which signaling ,31 Ectoper of R2 . In thisWnt10a and Wnt10b generated in this study showed various tooth phenotypes. Although, the double heterozygous mutant Wnt10a+/−;Wnt10b+/− mice did not exhibit any differences in maxillofacial morphology, number of teeth, and tooth morphology. Wnt10a−/−;Wnt10b+/− mice showed flattened cusps, defective root bifurcation, and a fourth molar (M4 teeth) in the mandible, as shown in Wnt10a single mutant mice; however, the flatness of cusps and taurodontism was considerably more severe than those in Wnt10a−/− mice. As both Wnt10a and Wnt10b are expressed in enamel knots and odontoblasts, these two genes may compensate for their roles in odontogenesis. In contrast, tooth number did not change in Wnt10b−/−mice. However, Wnt10a+/−;Wnt10b−/− mice exhibited a supernumerary tooth in mandibular diastema and size differentiation of the maxillary M1 and M2 teeth.The double mutants of Wise−/− or Lrp4 mutants had supernumerary teeth located in the diastema region mesial to M1 teeth [Wnt10a+/−;Wnt10b−/− mice had supernumerary teeth ahead of M1 teeth in diastema, suggesting that a similar molecular mechanism to Wise−/− or Lrp4 mutants may have occurred. However, the extra teeth of Wnt10a−/− and Wnt10a−/−;Wnt10b+/− mice are located behind the M3 teeth, which suggests that the underlying mechanism of supernumerary tooth formation in Wnt10a−/− and Wnt10a−/−;Wnt10b+/− mice might be different from that of other mutant mouse models. It is possible that the functional redundancy of Wnt10a and Wnt10b may control spatial patterning and the development of teeth.M1 teeth ,32. In tWnt10a and Wnt10b stimulate osteoblastogenesis via a b-catenin-dependent mechanism [Wnt10a-knockout mice show significant bone loss [Wnt10a−/− mice. Therefore, Wnt10a is considered to be important for the maintenance of postnatal bone volume [Wnt10b expression is observed in the bone marrow. Wnt10b-single-knockout mice also show loss of bone volume [Wnt10a or Wnt10b appear to have normal growth rates. Although Wnt10a+/−;Wnt10b+/−, Wnt10a−/−;Wnt10b+/− and Wnt10a+/−;Wnt10b−/− mice showed normal growth rates, only the double-knockout mutant Wnt10a−/−;Wnt10b−/− mice showed a marked decrease in body length and a weak appearance. This finding suggests that the cooperation of both Wnt10a and Wnt10b maintains systemic bone homeostasis.Both echanism . Wnt10a-one loss . Alveolae volume . Wnt10b e volume . HoweverMSX1, PAX9, and EDA, which are the causative genes of oligodontia in humans, demonstrate developmental arrest of tooth formation or a decrease in tooth number [WNT10A and WNT10B show tooth deficiencies; however, none of the knockout mutants have displayed a decrease in tooth number. Regarding other WNT family genes, Wnt5a is expressed in the teeth and palate. Although WNT5A GPVs have not been reported in human disease, Wnt5a−/− mice die a few hours after birth because of the cleft palate phenotype. The incisors and molars observed in these cases are reduced in size, with abnormally patterned cusps at P0 [Wnt10a−/−, Wnt10a−/−;Wnt10b+/− and Wnt10a+/−;Wnt10b−/− mice exhibited increased tooth numbers, such as M4 teeth behind the M3 teeth in the mandible or supernumerary teeth in diastema. The spatial patterning of teeth, characterized by the size and number of teeth and their cusps, has been described using a reaction–diffusion mechanism [Mice with knockouts of h number ,16. Patips at P0 . Wnt10a−echanism .Sostdc1−/− mice, which suggests that Shh affects preventing molar fusion downstream of Sostdc1. In addition, it was indicated that Shh works as a Wnt signaling antagonist via the upregulation of Dkk1 [Cho et al.  proposed of Dkk1 .Wnt10a−/−;Wnt10b−/− mice showed reduced size or the number of teeth. These phenotypes are very similar to Wnt-inhibitor Dkk1 overexpressed mice. The mandibular molars of Dkk1 overexpressed mice had significantly flattened and small cusps [Wnt10a−/−;Wnt10b−/− mice are affected by the Wnt-Shh-Sostdc1 negative feedback loop. Tabby, the Eda mutant mice also shows similar tooth phenotypes to Wnt10a−/−;Wnt10b−/− mice including smaller tooth and fewer cusps forming [Eda is a target gene of Wnt/β-catenin signaling, and Eda signaling may modulate multiple components of the integrated signaling network that regulates the balance of activators and inhibitors of tooth morphogenesis and patterning. Therefore, it is possible that severe signaling reduction may occur in Wnt10a and Wnt10b double mutants.ll cusps . This mi forming . Eda is Wnt10a and Wnt10b functions in the determination or repartition of tooth number. The findings from this study may prove to be of significance in understanding the feedback loop mechanism involved in the spatial patterning of teeth.Our study highlights the importance of both


IntroductionStudies show that malnutrition can lead to worsening morbidity and mortality in patients. However, to our knowledge, no large database study has been conducted describing the effects of malnutrition in patients with diverticulitis. In this article, we aim to assess the impact of pre-existing malnutrition on outcomes of patients admitted for diverticulitis.MethodsData between 2008 and 2014 from the Nationwide Inpatient Sample database were extracted. Inclusion criteria for both groups included patients with a primary diagnosis of diverticulitis using the International Classification of Diseases, Ninth Revision codes. Exclusion criteria included all patients less than 18 years of age. The test group consisted of patients with a primary diagnosis of diverticulitis and a concurrent diagnosis of malnutrition. In-hospital mortality, length of stay, total cost, and complications, including various forms of sepsis, perforation, bleeding, and GI bleeding, were compared between the two groups. Univariate and multivariate analyses were used to generate odds ratios. Multivariate analysis included age, sex, race, income quartile, and calculated Elixhauser scores. Elixhauser comorbidity scores predicting mortality and readmission were calculated based on weighted scores from 29 different comorbidities. Scores were compared between the two groups using univariate analysis.ResultsThere were a total of 1,520,919 patients in the study, of which 427,679 (2.8%) had a pre-existing diagnosis of malnutrition. On univariate analysis, there was a significant increase in mortality in patients with malnutrition . Additionally, patients with malnutrition appeared to have longer lengths of stay  and greater cost of hospitalization . Patients with malnutrition had greater rates of sepsis events , perforation , and GI bleed . On multivariate analysis, malnutrition appeared to significantly increase mortality .DiscussionPatients who present with diverticulitis with malnutrition appear to have significantly worse outcomes. We hypothesize that malnutrition leads to a shift in the gut microbiota, resulting in increased inflammation. As a result, these patients may have an increased risk of worse outcomes, such as sepsis and death. Addressing nutrition in patients with diverticulosis or those with a history of diverticulitis may improve outcomes.This abstract was previously presented at the Digestive Disease Week Conference on May 22, 2022. Abstracts accepted at the conference were published in supplements of the journals Gastroenterology and GIE: Gastrointestinal Endoscopy. Diverticulosis involves the formation of small pouches at points of weakness within the wall of the colon, specifically at the site where the muscularis mucosae are traversed by vasa recta -3. IncreMalnutrition describes the deprivation of the nutrients, vitamins, and minerals required for the body to maintain tissue function and health . MalnutrLimited research endeavors have explored the link between nutritional status and diverticulitis. Among those projects, a smaller number have established a positive correlation between pre-existing malnutrition and the onset of acute diverticulitis . FurtherThis article was previously presented as a poster at the Digestive Disease Week Conference on May 22, 2022. Abstracts accepted at the conference were published in supplements of the journals Gastroenterology and GIE: Gastrointestinal Endoscopy.Data/source populationData between 2008 and 2014 from the Nationwide Inpatient Sample (NIS) were extracted. Inclusion criteria for both groups encompassed patients with a primary diagnosis of acute diverticulitis using the International Classification of Diseases, Ninth Revision (ICD-9) codes, and those aged 18 years old or older.The experimental group was comprised of patients with a primary diagnosis of acute diverticulitis and a second diagnosis of malnutrition. The following confounders were controlled for upon data analysis: age, gender, race, and median household income.Statistical analysisCategorical and continuous variables were analyzed via chi-square analysis and Student's t-test, respectively. In-hospital mortality was compared between the experimental and control groups. Elixhauser Comorbidity Index (ECI) scores, designed to predict mortality and readmission rates, were calculated based on weighted scores from 29 different comorbidities. ECI scores were compared across both groups via Student's t-test. Multiple comorbidities were also assessed between both groups. Multivariate analyses using binary logistic regression were conducted with death as the primary outcome. ECIs were generated using SAS OnDemand for Academics  and Statistical Package for the Social Sciences (SPSS) version 28.0.0 . Multivariate analysis factoring in age, sex, ethnicity, income status, and ECI scores were used to further characterize and assess the effects of malnutrition on mortality.In terms of patient characteristics, those with malnutrition were older (68.86 years versus 59.29 years). Most patients in both groups were females; however, those with malnutrition had a greater proportion of females (66.8% versus 57.3) as opposed to those without malnutrition Table . The majPatients with malnutrition hospitalized with acute diverticulitis had greater mortality than those without malnutrition hospitalized for the same issue (3.9% versus 0.4%) Table . ComplicECI mortality (16.87 versus 2.33) and readmission (27.77 versus 7.9) rates were higher in those with malnutrition . Additionally, age, female status, Hispanic, Native American, third and fourth quartile income status, and ECI scores were all significant (Table Adequate nutritional intake is necessary for the maintenance of cell homeostasis and tissue function. Proper nourishment depends on the intake of a variety of micronutrients such as vitamins and metals, as well as macronutrients such as proteins, lipids, and carbohydrates ,7,10-13.Identifying malnutrition is vital because of its association with poor inpatient outcomes, including prolonged length of stay, inpatient mortality, mortality within 180 days post-discharge, and higher rates of readmission ,14,15. FOnce malnutrition is identified, ascertaining an underlying etiology may assist in developing an adequate treatment plan. Acute diverticulitis is one such cause that is intricately linked with nutritional status. It is an uncommonly recognized cause of nutritional deficiency, for it most often occurs in overweight patients . HoweverEnterobacteriaceae within the gut microbiome [Bacteroides and Streptococcus, has been associated with diverticular disease [Various diets have also been hypothesized to affect the composition of gut microbiota . For exacrobiome . A prepo disease . Further disease . The patIn our analysis, we found that malnourished patients had longer hospital stays, greater hospital charges, and higher rates of readmissions after initial discharge. Furthermore, we found that malnutrition in patients hospitalized for acute diverticulitis was significantly associated with increased inpatient mortality, as well as rates of complications, including bowel perforation, fistula formation, gastrointestinal bleeding, intra-abdominal abscess formation, ileus, colonic obstruction, respiratory failure, and sepsis. Increased rates of complications in the setting of poor nutritional status are likely multifactorial. As previously established, slowed colonic transit results in the buildup of intraluminal colonic pressure, while poor nutritional diets can increase the prevalence of pro-inflammatory bacteria within the microbiome -21. ThesThis study is limited by our use of the NIS database, which utilizes ICD-9 codes to identify diagnoses. As malnutrition is difficult to clinically diagnose, it may be underreported and therefore underrepresented in our sample size. Furthermore, malnutrition is often diagnosed either by physical exam or laboratory assessment; however, multiple diagnostic tools also exist to arrive at this diagnosis ,22,23. DMalnutrition has been associated with worse outcomes in those hospitalized for acute diverticulitis, including mortality, complication rates, length of stay, and hospital costs. Poor nutritional status should be identified to better stratify those at increased risk of complications; however, more objective methods of diagnosing malnutrition should be identified. Potentially subjective lab findings, such as albumin, which can be altered for multiple reasons, should not be used in all patients to identify their nutritional status. Objective tools that are specific to diagnosing malnutrition and can stratify the degree would help determine if its association with diverticular disease is step-wise in nature. There is no established benefit to correcting poor nutritional status in this patient population. Further studies are required to determine if nutritional supplementation would benefit malnourished patients hospitalized with diverticulitis.


Alcohol abuse is not only harmful to the consumer but may also negatively impact individuals in the drinker’s social environment. Alcohol’s harm to others is vital to consider when calculating the true societal cost of alcohol use. Children of parents who have alcohol use disorder tend to have an elevated risk of negative outcomes regarding, e.g., health, education, and social relationships. Research on the general youth population has established a link between parental drinking and offspring alcohol use. However, there is a lack of knowledge regarding other outcomes, such as health. The current study aimed to investigate the associations between parental drinking and children’s psychological and somatic complaints, and perceived stress.Data were derived from a nationally representative sample, obtained from the 2010 Swedish Level-of-Living survey (LNU). Parents and adolescents (ages 10–18) living in the same households were interviewed independently. The final study sample included 909 adolescents from 629 households. The three outcomes, psychological and somatic complaints and perceived stress, were derived from adolescents’ self-reports. Parents’ self-reports of alcohol use, both frequency and quantity, were used to categorise adolescents as having abstaining, low-consuming, moderate-drinking, or heavy-drinking parents. Control variables included adolescents’ gender, age, family structure, and household socioeconomic status. Linear and binary logistic regression analyses were performed.Parental heavy drinking was more common among adolescents living in more socioeconomically advantaged households and among adolescents living with two custodial parents or in reconstituted families. Adolescents with heavy-drinking parents reported higher levels of psychological and somatic complaints and had an increased likelihood of reporting stress, compared with those having moderate-drinking parents. These associations remained statistically significant when adjusting for all control variables.The current study’s results show that parental alcohol consumption is associated with poorer offspring adolescent health. Public health policies that aim to reduce parental drinking or provide support to these adolescents may be beneficial. Further studies investigating the health-related outcomes among young people living with heavy-drinking parents in the general population are needed to gain more knowledge about these individuals and to implement adequate public health measures.The online version contains supplementary material available at 10.1186/s12889-023-15097-w. Alcohol use is a leading risk factor for the global burden of disease and entails a substantial economic cost, both directly and indirectly, to many societies , 2. The Young people are especially vulnerable to others’ drinking and much research has focused on children of parents with alcohol use disorder. The existing literature reveals that these individuals fare worse than other offspring in important life areas such as health, education, and social relationships . Health problematic drinking, rather than overall consumption, are methodological features that might underestimate the total harms that parental drinking entails since adolescents are not likely to have full knowledge about their parents’ alcohol habits and the parent-child relationship could influence the perception of their parents’ drinking. One exception is a study done on Korean data, which found that parent-reported frequency of drinking was associated with adolescent self-perception of stress [Studies looking beyond clinical samples have found a clear and consistent association between parental alcohol use and adolescent drinking in the general youth population . Howeverf stress . Nonethef stress . Examinif stress . Subjectf stress , and indf stress , 19. Recf stress , 21.This study aims to examine the associations between parents’ self-reported quantity and frequency of alcohol consumption and offspring psychological and somatic complaints, and perceived stress, using data collected from parent(s) and adolescents separately.The Data were obtained from the 2010 Swedish Level-of Living survey (LNU). LNU is based on a nationally representative sample of 0.1% of the population aged 18–75 and is performed approximately every 10 years, with the 2010 dataset being the most recently available . PersonaFor the current study, we combined data from the LNU, Partner-LNU, and Child-LNU of 2010. As data were gathered from the co-habiting partner of the main responding parent, variables based on parental information can include answers from both custodial and/or step-parents. The LNU 2010 survey included 7,253 individuals in the sampling frame and interviews were conducted with 4,415 of these, corresponding to a response rate of 60.9%. Furthermore, 3,347 spouses or partners to the main respondent were identified and 2,522 of these completed the Partner-LNU 2010 (75.4%). In total, 1,238 adolescents were offered to participate in the Child-LNU 2010 and 923 agreed to take part (71.9%). After further exclusion due to internal non-response on any of the variables used in the current study, the analytical sample consisted of 909 adolescents in 629 households. Among these, 640 adolescents (70.4%) had linked information from two parents. Among those living with two custodial parents (n = 634), 83.4% had linked information from both parents.The dependent variables in this study, psychological complaints, somatic complaints, and perceived stress, were based on adolescents’ self-reports from the Child-LNU.Psychological complaints were constructed from three items: ‘I often feel sad or down’; ‘I am often tense or nervous’; ‘I am often grouchy or irritated’. Response alternatives were: (1) ‘Matches exactly’, (2) ‘Matches roughly’, (3) ‘Matches poorly’, and (4) ‘Does not match at all’. Responses were then reversed and added to an index ranging from 3 to 12, with higher values indicating more psychological complaints . Missing answers on at most one of the items were replaced with the individual mean of the remaining items.Somatic complaints were constructed from three items: ‘In the last 6 months, how often have you had the following complaints?’: ‘Headache’, ‘Stomach-ache’, ‘Difficulties in falling asleep’. Respondents were given five response alternatives: (1) ‘Every day’, (2) ‘Several times a week’, (3) ‘Once a week’, (4) ‘About once a month’, and (5) ‘More seldom or never’. Responses were then reversed and added to an index ranging from 3 to 15, with higher values indicating more frequent somatic complaints . Missing answers on at most one of the items were replaced with the individual mean of the remaining items. These measures of psychological and somatic complaints have been used previously .Perceived stress was captured by the question: ‘During the last 6 months, how often have you felt stressed?’. Response alternatives were the same as for somatic complaints. Adolescents who felt stressed more than once a week were categorised as reporting perceived stress .or 2–4 times a week and at least 3 glasses per occasion, were categorised as heavy drinkers. Using this cut-off, parents in the heavy-drinking category consume at least 6 glasses per week. While this figure is well below the Swedish guidelines for what counts as heavy drinking it is important to acknowledge that the response categories given contain variation that is impossible to avoid in the construction of the categories. One individual who answers ‘2–4 times a week’ could drink twice as often as another individual who ticks the same box, for example. The answers that respondents provide are also likely affected by recall bias due to difficulties in remembering how often and how much one drinks, the propensity to underestimate one’s consumption of alcohol because of social desirability, and the hard task of calculating an average number of drinking occasions and drinks for the last 12 months. The difficulty of accurately measuring individuals’ alcohol consumption in epidemiology is known [or 2–4 times a week but less than 3 glasses per occasion). These questions about alcohol use have been employed in prior studies, separately and combined, to assess drinking patterns among parents, young adults, and older adults [The independent variable, parental alcohol use, was based on parent-reported information and constructed from three items in the LNU and Partner-LNU. Parents were categorised as: abstainers; low consumers; moderate drinkers; or heavy drinkers. The first question was: ‘Do you at any time drink wine, strong beer/cider, or liquor?’ and those who answered ‘Yes’ responded to two additional questions: ‘During the last 12 months, about how often have you consumed some amount of alcoholic beverage, that is: wine, strong beer, strong cider or liquor?’  and ‘On such occasions, how many glasses do you usually drink? One glass can be 1 glass of wine, 1 bottle or can of beer, or 1 schnapps or drink’. Non-drinking parents were categorised as abstainers and those who drank less than once a month as low consumers. We wanted to keep these types of drinking patterns separate since current non-drinking or low consumption may be a result of prior heavy consumption and/or indicative of characteristics that may influence offspring health, such as severe health problems among parents or small social networks , 26. Paris known . Consequr adults –30. For Adolescents’ gender and age, as well as family structure, household social class, household cash margin, parental level of education, and parental unemployment were included as control variables, based on information in LNU and Partner-LNU. Family structure distinguished between adolescents living in households with two custodial parents, one custodial parent, or in reconstituted families . Household social class was based on parents’ occupations and classified into four categories: manual workers, farmers and entrepreneurs, intermediate/lower non-manual workers, and higher non-manual workers. For those with information from two parents, the classification was based on the principle of dominance order presented by Erikson . Lack ofb) and odds ratios (OR) with 95% confidence intervals (CI) are presented. All statistical analyses were carried out in Stata version 16.1.First, the associations between parental alcohol use and all control variables were examined through bivariate cross-tabulations with chi2-tests. Next, linear and binary logistic regression analyses were performed with psychological and somatic complaints and perceived stress as the dependent variables. For each outcome, crude analyses (including one independent/control variable at a time) and an adjusted model  were conducted. To account for the fact that some adolescents lived in the same households (being siblings or step-siblings), robust standard errors were estimated, clustering at the household level. Regression coefficients  and of somatic complaints , as well as with a higher likelihood of reporting perceived stress . These associations were moderately amplified and remained statistically significant in the adjusted models . Additional analyses revealed that adolescents with heavy-drinking parents also reported higher levels of psychological complaints (p < 0.05) and somatic complaints (p < 0.01) compared with those who had abstaining parents (not shown in table). Compared with those whose parents who were moderate drinkers, adolescents with low-consuming parents reported higher levels of somatic complaints in the crude analysis , but this association was attenuated and turned non-significant in the adjusted model . Having low consuming parents was not associated with psychological complaints or perceived stress, neither in the crude nor in the adjusted analyses.Table Turning to the associations between the sociodemographic variables and the health outcomes in the adjusted models; girls reported more psychological and somatic complaints and were more likely to experience perceived stress compared with boys. Older adolescents experienced more psychological complaints and had a higher likelihood of reporting perceived stress. Living with only one parent was associated with somatic complaints and living in a reconstituted family was associated with an increased likelihood of reporting perceived stress. Having parents with manual occupations was associated with psychological complaints. Lastly, having parents with compulsory or vocational education was inversely associated with psychological complaints.We also performed two types of sensitivity analyses to check the robustness of the results . Firstly, a series of linear and binary logistic regressions, similar to those presented in Table This study examined associations between parental drinking and offspring subjective health complaints and perceived stress, using information collected separately from parent(s) and adolescents. We distinguished between individuals whose parents were abstainers, low consumers, moderate drinkers, and heavy drinkers. Results from linear and binary logistic regressions showed that having heavy-drinking parents, compared with having moderate-drinking parents, was associated with an increased likelihood of reporting psychological and somatic complaints and perceived stress, even when adjusting for sociodemographic characteristics. These findings reflect earlier studies that have found associations between problematic parental drinking and adverse health among offspring in the general population –15 and aTaking inspiration from prior discussions on adverse outcomes among individuals of parents with alcohol disorder, we propose several underlying mechanisms that may explain our finding that adolescents with heavy-drinking parents were more likely to report subjective health complaints and perceived stress. Parental heavy drinking can negatively affect the parent-child relationship, increase the risk of child abuse or neglect, and contribute to a stressful home environment , 8. Alcoproblems and the present study using a measure based on parent-reported frequency and quantity of alcohol consumption. This reasoning may also be interpreted in light of the alcohol harm paradox [The current study detected no differences in parental drinking by offspring gender or age. However, heavy-drinking parents were more prevalent in more socioeconomically advantaged households and among adolescents living with two custodial parents or in reconstituted families. Contrasting these findings, Pisinger et al.  reported paradox , i.e., t paradox .because of their child’s ill health or externalising behaviour, or a strained parent-child relationship in a reverse causal pathway [This study benefits from using data based on a nationally representative sample, collected from parents and adolescents separately. It is also one of few studies that have examined associations between parental drinking and offspring health in the general population rather than among individuals of parents with alcohol disorder. Additionally, the data contained reliable measures of control variables, such as on socioeconomic position. Nonetheless, there are some limitations that should be considered. Firstly, due to using cross-sectional data, conclusions regarding causality are difficult to draw. We cannot ascertain that parental drinking patterns preclude offspring subjective health complaints and stress. It is possible that a parent starts to drink heavily  pathway , 39. In Secondly, since the data used in the current study are from 2010, it is possible that the results are not valid presently due to changes in, e.g., alcohol habits among parents, family dynamics, or relevant compensating factors. Although some small changes are visible in drinking patterns among Swedish adults since 2010, e.g., total consumption has decreased slightly in most groups younger than 60 years, and the proportion of females who engage in frequent binge drinking has increased , 41, theThirdly, the categories of parental alcohol use were not based on any established guidelines or previous studies. In Sweden, heavy drinking has been defined as consuming more than 9 or 14 glasses per week for women and men, respectively. With this definition, about 10% of the adult population are classified as heavy drinkers . Due to Moreover, recall and/or desirability bias in regards to the items that measure parental drinking might also be present. Apart from the difficulty in remembering consumption levels, revealing one’s alcohol habits could also be shameful. Typically, survey methods in estimating alcohol consumption are associated with underreporting, which in turn, could imply that the levels of consumption presented in the current study are an underestimation .Finally, it should also be acknowledged that even though the Swedish Level-of-Living Survey was based on a nationally representative sample, the attrition in several steps may have compromised the representativeness of the data. The fact that the study was conducted in Sweden, with somewhat lower rates of alcohol consumption than many other European countries , also neContinued research on alcohol’s harms to others, and especially on adolescents with heavy-drinking parents, is important. Enhanced knowledge about the total societal consequences of alcohol consumption is essential for policy makers to be able to make informed decisions , 45. StuAlcohol’s harms to others is gaining more recognition and is important to consider for public health advocates. This study demonstrated associations between parental heavy drinking and adolescent subjective health complaints and perceived stress. Adolescents living with heavy-drinking parents constitute a vulnerable group worthy of adequate public health responses. Implementing policies aiming to support these individuals may be beneficial.Below is the link to the electronic supplementary material.Supplementary Material 1


Maternal lipid levels during pregnancy are critical for fetal development. Recent studies revealed that high-density lipoprotein cholesterol (HDL-c) levels during pregnancy were negatively correlated with birthweight. High-density lipoprotein 2 cholesterol (HDL2-c) is one of the major subclasses of HDL-c, and its relationship with birthweight is unclear. Association of HDL2-c concentration in the first trimester and risk of large for gestational age (LGA) was explored.This study recruited pregnant women who registered in Fuxing Hospital from October 2018 to January 2020, had regular obstetric examinations during pregnancy, and delivered between June 2019 and September 2020. Finally, 549 participants were recruited for the study. Maternal demographic characteristics and venous blood were collected at the 6th-14th gestational week, and serum total cholesterol (TC), triglyceride (TG), HDL-c, HDL2-c, high-density lipoprotein 3 cholesterol (HDL3-c), and low-density lipoprotein cholesterol (LDL-c) concentrations were detected. Neonatal characteristics were collected at delivery. A logistic regression model was used to explore the relationship between the first trimester HDL2-c concentration and LGA incidence. A nomogram was developed, and the performance was evaluated with a concordance index.P = 0.001) when adjusted for age, prepregnancy body mass index (BMI), and parity. A nomogram was generated using all these risk factors. The area under the curve (AUC) was 0.663 (95% CI: 0.593–0.732).Seventy-five mothers delivered LGA infants, and the LGA incidence was 13.66%. LGA mothers had significantly lower serum HDL-c and HDL2-c concentrations than appropriate for gestational age (AGA) mothers. A logistic regression model showed that HDL2-c concentration was negatively correlated with LGA risk (odds ratio (OR) = 0.237, 95% confidence intervals (CI): 0.099–0.567, Maternal HDL2-c concentration in the first trimester was negatively correlated with the risk of LGA.The online version contains supplementary material available at 10.1186/s12944-022-01688-w. High-density lipoprotein cholesterol (HDL-c) refers to cholesterol and cholesterol esters carried by HDL particles, and recently researchers found that maternal HDL-c concentrations were negatively correlated with birthweight. Misra et al.  found thHDL particles are heterogeneous and consist of multiple subcomponents of different sizes and densities. Based on the difference in density, HDL can be divided into HDL2 and HDL3 by ultracentrifugation. HDL2 has a larger size, smaller density, and weaker antioxidant capacity than HDL3. Whether high-density lipoprotein 2 cholesterol (HDL2-c) or high-density lipoprotein 3 cholesterol (HDL3-c) plays a significant role in fetal growth and birthweight is unclear. However, some evidence suggests that HDL2-c concentration may be a critical factor. A longitudinal study showed that the lengths and head circumferences of newborns correlated negatively with the proportion of HDL2a subclasses in mothers’ plasma before delivery . AnotherLarge for gestational age (LGA) refers to those newborns whose birthweight are higher than the 90th percentile of the mean birthweight or 2 standard deviations above the mean birthweight of neonates with the same gestational age. Recently, the incidence of LGA has been increasing in China, reaching 8.2%-17.7% in different regions . LGA cauThis study recruited pregnant women who registered at Fuxing Hospital from October 2018 to January 2020, had regular obstetric examinations during pregnancy, and delivered between June 2019 and September 2020 as the research population. The criteria for inclusion and exclusion are as follows. The following inclusion criteria were employed: 1) 20–40 years of age; 2) singleton pregnancy; 3) natural fertilization; and 4) first blood collection was performed before the 14th gestational week. The following exclusion criteria were employed: 1) women with infectious disease or other severe disease; 2) fetal malformation or birth defects; and 3) Apgar score < 7 at the 5th min.Finally, 549 participants were recruited for the study.A questionnaire survey was conducted to obtain maternal demographic characteristics at their first hospital visit. Data collected included age, height, prepregnancy weight, gravidity, parity, disease history, education background and occupation. Neonatal data at delivery, including newborn sex, birthweight, birth length, gestational weeks, gestational weight gain (GWG), mode of delivery and perinatal outcome, were collected in this study.2 (98.7 mg/ml), and dextran sulfate (12 mg/ml), was added to 0.3 ml of serum. The mixture was settled at room temperature for 30 min, and centrifuged at 10,000 rpm at 4 °C for 10 min. An aliquot of the supernatant was taken for HDL3-c measurement. To correct for reagent dilution, the HDL3-c value was multiplied by 1.2. Value of HDL2-c concentration was calculated by subtracting HDL3-c from HDL-c.Fasting blood samples of pregnant women were collected for measurement of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and HDL-c serum concentrations at the 6th-14th weeks. The HDL3-c concentration was measured using a single precipitation method . In brieP value < 0.05 was defined as significantly different. A nomogram for LGA risk was created based on the logistic regression model. The nomogram performance was evaluated by a concordance index.Data were analyzed by SPSS 26.0 and R software. The independent sample t test and chi-square test were used to analyze the differences between the appropriate for gestational age (AGA) and LGA groups. Kendall’s tau_b correlation was used to analyze the associations between LGA incidence and maternal concentrations of HDL-c, HDL2-c, and HDL3-c as well as the ratio of HDL2-c/HDL3-c. The logistic regression model was adjusted based on maternal age, prepregnancy body mass index (BMI), gestational weight gain and parity. A 2 and 13.25 ± 4.97 kg in the LGA and AGA groups, and no significant difference was detected. The average birth weight, head circumference and birth length of LGA group were significantly higher than those of AGA group, as expected. In terms of parity, neonatal sex, as well as mode of delivery, no significant difference was detected. All the results were shown in Table In total, 75 mothers delivered LGA infants among all 549 pregnant women, and the LGA incidence was 13.66%. The average age, prepregnancy BMI and GWG of the pregnant women were 31.4 ± 3.7 years old, 21.84 ± 2.95 kg/mCompared to AGA mothers, LGA mothers had significantly lower serum HDL-c (1.384 ± 0.345 mmol/L vs. 1.553 ± 0.454 mmol/L) and HDL2-c concentrations (1.031 ± 0.296 mmol/L vs. 1.193 ± 0.423 mmol/L)    , the LGA incidence in the two groups with the highest HDL-c levels (1.4501 ≤ HDL-c ≤ 1.7399 mmol/L and HDL-c ≥ 1.7400 mmol/L) were significantly lower , yet no correlation was found between HDL3-c concentration and the LGA incidence.Kendall’s tau_b correlations were used to explore the association between the incidence of LGA and HDL-c, HDL2-c, and HDL3-c concentrations as well as the ratio of HDL2-c/HDL3-c. Concentrations of HDL-c, HDL2-c and HDL3-c and the ratio of HDL2-c/HDL3-c were grouped into quartiles. Table P = 0.001) was a protective factor for LGA. A 1 mmol/L increase in HDL2-c concentration was associated with a 23.7% decrease in the incidence of LGA (95% CI 0.099–0.567). GWG  was positively associated with the risk of LGA . FF provides cholesterol for steroid production , and regBased on the difference in density, HDL can be divided into HDL2 and HDL3 by ultracentrifugation. Density of HDL2 was 1.063–1.125 g/ml and density of HDL3 was of 1.125–1.210 g/ml. HDL2 has a larger size and weaker antioxidant capacity than HDL3 . Althougp = 0.001). Each 1 mmol/L increase in HDL2-c concentration decreased the risk of LGA by 23.7%. The study also created a nomogram for the risk of LGA using the factors included in the logistic regression model: age, prepregnancy BMI, parity, GWG and HDL2-c concentration in the first trimester. A concordance index was used to evaluate nomogram performance and the AUC was 0.693, indicating a certain discriminative ability. The nomogram suggested that high GWG and low HDL2-c concentrations were the major risk factors for LGA.In the present study, HDL2-c concentrations of LGA mothers were significantly lower than those of AGA mothers, but HDL3-c concentrations didn’t differ between two groups. In addition, a negative correlation between HDL2-c concentration and the risk of LGA was found in this study. The logistic regression model showed that when adjusted by maternal age, prepregnancy BMI, and parity, HDL2-c concentration was negatively correlated with the risk of LGA (OR = 0.237, 95% CI: 0.099–0.567, The decrease in total antioxidant capacity of HDL particles may be the mechanism involved in the association between HDL2-c levels and the proportion of HDL2-c and fetal development. HDL antioxidant function is mainly realized by ApoA-I, PON1, PAF-AH and other components. Studies have found that ApoA-I is more enriched in small and dense HDL3-c compared to HDL2a and HDL2b , and PONIn recent years, the incidence of LGA in infants has been increasing in China, reaching 8.2%-17.7% in different regions. The incidence of LGA in our study was 13.66%. Women who delivered LGA infants are more likely to have pregnancy complications, including cephalopelvic disproportion and postpartum hemorrhage. Regarding birth outcomes, LGA infants were more likely to get shoulder dystocia, neonatal injury, birth asphyxia and neonatal death. LGA was confirmed to be associated with maternal hyperglycemia, hypertriglyceridemia, obesity, excessive GWG and advanced age. Although the results showed a reverse association between maternal cholesterol levels and LGA incidence, it is important to control cholesterol levels during pregnancy given that abnormal elevation showed an adverse effect on birthweight, which may result in fetal growth restriction, low birth weight and SGA.Previous studies have typically focused on TC and HDL-c levels in mid-pregnancy or late pregnancy and explored their relationship with birthweight. The present study focused on maternal HDL2-c concentrations in the first trimester and found a negative association with the risk of LGA.The present study not only found a negative association between maternal HDL-c concentration and LGA incidence, but also revealed that maternal HDL2-c concentration in the first trimester was negatively associated with the risk of LGA. However, this study had some limitations. First, when exploring the association between HDL2-c concentration and birthweight, SGA infants were excluded. In addition, information on pregnant women lifestyle wasn’t collected. For instance, pregnancy diet and physical activity, and these may be confounders. It is necessary to explore the relationship between maternal HDL2-c concentration and SGA incidence to elucidate its effect on birthweight, and maternal lifestyle should be taken into account in these studies.In conclusion, high maternal HDL-c and HDL2-c levels in the first trimester were negatively correlated with the risk of LGA. For pregnant women, it is important to detect and monitor maternal HDL2-c concentrations in the early pregnancy to evaluate embryonic and fetal development and avoid adverse birth outcomes.Additional file 1.Additional file 2.Additional file 3.


Heart Rate Variability (HRV) has become an important risk assessment tool when diagnosing illnesses related to heart health. HRV is typically measured with an electrocardiogram; however, there are multiple studies that use Photoplethysmography (PPG) instead. Measuring HRV with video is beneficial as a non-invasive, hands-free alternative and represents a more accessible approach. We developed a methodology to extract HRV from video based on face detection algorithms and color augmentation. We applied this methodology to 45 samples. Signals obtained from PPG and video recorded an average mean error of less than 1 bpm when measuring the heart rate of all subjects. Furthermore, utilizing PPG and video, we computed 61 variables related to HRV. We compared each of them with three correlation metrics , adjusting them for multiple comparisons with the Benjamini–Hochberg method to control the false discovery rate and to retrieve the q-value when considering statistical significance lower than 0.5. Using these methods, we found significant correlations for 38 variables  using time-domain, frequency-domain, and non-linear methods. Heart Rate Variability (HRV), a quantitative marker of autonomic activity that measures the physiological phenomenon of variation in the time interval between heartbeats, has become a very important risk assessment tool. A reduced HRV can be associated with a poorer prognosis for multiple conditions, while more robust periodic changes in the R-R interval show signs of good health ,2,3,4. HAccording to the American Heart Association, HRV can be measured using time-domain, frequency-domain, and non-linear methods , with eaThis study aimed to find a way to obtain HRV measurements from a device other than the main tool currently used, the Holter ECG ,9,10,11.The main contribution of this work is that by performing a correlation analysis, we determined that the HRV features extracted from video were comparable in quality to those obtained through PPG when using a database with PPG measurements derived from a pulse oximeter . SignifiTo generate our dataset, we used a commercial pulse oximeter to obtain the PPG signal and heart rate of each subject. We also used a camera with a frame rate of 30 fps; this rate permits smooth transitions between frames, which creates a smoother signal output, and a resolution of 1280 × 720 to record the faces of the participants throughout the entirety of the test. The higher the resolution, the more computational cost it presents. The test was designed to have a ten-minute duration in order to capture information in the very-low frequency range. Due to the effect of ballistocardiographic artifacts in PPG signals and how they can affect the obtention of the signal [Our methodology is shown in pyHRV toolbox [We used the same methodology to extract HRV features from PPG signals used in our previous work , in whic toolbox . The per toolbox .Viola–Jones face detectors variation from the Haar cascade classifier [The methodology employed to extract the HRV features from the video began with a face detection stage. Using face landmarks with OpenCV and the assifier , we wereThe next stage consisted of a color augmentation method using the Eulerian Video Magnification algorithm developed by Freeman et al.  and applFrom the color-augmented video, we only extracted the information from the red channel, given that according to Feng et al. , the redConsidering that the pulse oximeter study and the video recording did not start and finish at the exact same time, there may have been some misalignment between the two signals. Therefore, we performed a time adjustment, in which the longest signal was trimmed (the same amount at the beginning and at the end of the recording) to match its counterpart. We also stratified the peak detection results on a per-minute basis in order to identify large sources of noise and possible variation between signals.Benjamini–Hochberg method to control the false discovery rate (FDR) by considering statistical significance when the adjusted p-value  was lower than 0.5.The mean error (Me), root mean square error (RMSE), and standard deviation (SD) of the heart rate obtained using each database were computed. Additionally, the correlation of each variable between datasets was calculated using the Kendall, Pearson, and Spearman tests. In order to account for multiple comparisons, we used the In this section, we will describe the results obtained at each stage of our methodology since it is crucial to detect any possible errors that could cause reliability issues when measuring HRV, either at the face detection stage, the color augmentation stage, or at the peak detection stage.Each video was inspected qualitatively when obtaining the ROI. All cropped videos passed our overall quality inspection and showed the forehead, eyes, nose, and part of the mouth of the subjects at almost all times, as shown in In order to evaluate the performance of the color augmentation stage, we compared the number of peaks detected from the processed video signal to those computed from the PPG signal, both globally and locally (1 min windows). However, we first performed a qualitative inspection to make sure that the red channel of the processed video yielded the expected results . Additionally, we visually compared the shape and period of the video and PPG signals, as shown in After retrieving the signals from both the pulse oximeter and the video, we located the peaks of each sample. We also trimmed the longest signal of each pair of results per observation in order to align them time-wise. Additionally, we performed the same comparison per 1 min window in order to detect specific time lapses in which there were significant differences between both signals. After computing the overall performance metrics, we obtained the correlation of each variable between both datasets. In total, 38 features were regarded as having a significant correlation between sources under the three different tests after adjusting for multiple comparisons. Furthermore, Finally, For the time-domain methods, the nine features that were significant under the three tests after adjusting for multiple comparisons can be seen in Welch method to calculate the power spectral density (PSD).For the frequency-domain methods, there were 26 significant features. autoregressive method to calculate the PSD.Lomg–Scargle method to calculate the PSD, Regarding the use of the Lastly, there were three significant features from the non-linear methods, all derived from a Poincaré plot, as seen in Our results show that the signal derived from the video had a very similar composition in terms of the locations of peaks to the signal derived from the commercial pulse oximeter, as determined by their smaller than 1 bpm average difference. To truly test the performance of the peak detection method we proposed, a comparison was made to other previously developed methods. From After performing a deeper analysis, in which the results were compared in 1 min windows, there was a tendency for the video to compute more peaks at the start and end of each study. This is probably due to the subjects settling into their chairs at the beginning of the study or preparing to get up by the end of it. These situations can lead to the video being cropped poorly, therefore obtaining a signal that does not relate to the skin of the subject, causing the signal from the R channel to provide false information. Nonetheless, even when taking this situation into account, the computation of heart rate was accurate, which means that when taking the correct time intervals and after cleaning the signal, we were able to compute the heart rate of a person as well as a pulse oximeter can.p-value adjustment for multiple comparisons. The features extracted from the PPG signal derived from the pulse oximeter were significantly correlated to those derived from the video. Moreover, those features included information generated using multiple methods: time-domain methods, frequency-domain methods, and non-linear methods. Specifically, in the frequency-domain, there were a considerable number of useful correlations in the variables related to Welch’s periodogram, a method used for spectrum monitoring [Additionally, we demonstrated that we were able to measure 38 HRV features with a significant correlation between sources of information; we considered three correlation tests and nitoring ,37, and nitoring . In addinitoring  and thatnitoring . For thenitoring ,42,43 annitoring .This work has some limitations; we only used information from one of the three channels of the video, while some authors have recommended mixing both the red and green channels to filter the noise of sudden movements from the subject due to the wavelength dependency of reflection PPG and optics . AnotherIn this work, we demonstrated that the HRV information derived from a PPG signal is significantly correlated to those same features when derived from a video. We performed 45 studies that included a 10 min session in which the subjects were connected to a pulse oximeter and looked into a camera. Peaks were detected from the PPG signal that the pulse oximeter yielded and were validated against a manually annotated dataset. Peaks were detected from the R channel of the video using the same methodology after a face detection and color augmentation stage that aimed at focusing on the face of the subjects and amplifying the subtle color changes in the skin caused by blood flow. On average, an error of less than 1 bpm was found when calculating the heart rate using each signal independently. Furthermore, HRV features were extracted from each signal using time-domain, frequency-domain, and non-linear methods. When compared using Pearson, Spearman, and Kendall correlations tests, and after adjusting for multiple comparisons, 38 of the 61 extracted features had a significant correlation in all three tests, including features from the three types of methods tested. These results are promising when it comes to possible applications, as this methodology could be employed in experiments related to the regulation of autonomic balance, blood pressure, gas exchange, and respiratory rate, as well as gut-, heart-, and vascular-related issues.


Technological developments in high-content biological and data platforms have led to the generation of large-scale multi-omics datasets in radiomics, genomics, epigenomics, transcriptomics, proteomics, metabolomics, and phenomics . CollectLi et al. explored a putative role for circular RNA (circRNA) in predicting the immune landscape of lung adenocarcinoma. Their data suggests that a circRNA-related risk score model is associated with the level of immune cell infiltration in the tumor that could impact the efficacy of adjuvant treatments . 2) Chen et al. studied the impact of germline copy number variants (gCNV) on the prognosis of patients with non-small cell lung cancer (NSCLC). They developed a prognostic nomogram model and validated their findings in an external cohort. Whether the two gCNVs they have identified, CNVR395.1 and CNVR2239.1, regulate or are accidentally associated with  NSCLC phenotypes require experimental validation. 3) Ye et al. examined the prognostic utility of a signature of ferroptosis, a form of programmed oxidation-related cell death associated with iron accumulation, a decrease in antioxidant cellular capacity, and the accumulation of lipid peroxidation or reactive oxygen species (ROS). In addition to clinical and functional studies validating aspects of this signature, a nomogram that incorporated clinical features provided reasonable concordance with overall survival. 4) Lastly, Wang et al. studied the association of long non-coding RNAs (lncRNA) with prognostication in NSCLC. They reveal lncRNA that are associated several clinical and pathological variates including histology, tumor size, stage, and, relatedly, overall survival. Altogether, these studies represent varied attempts to link omic variates, biological pathways, and patient outcomes. Many more attempts that integrate the panoply of omic variates from bulk and single cells coupled with well annotated clinical outcomes are needed.The contributions within this Research Topic are in line with ongoing efforts to better characterize the associations between omic determinants and tumor phenotypes. 1) The convergence of technology and large-scale dataset development has created an unparalleled opportunity to couple omic information with clinical outcomes for many patients with cancer. Rigorous evaluations will require many additional validations and innovations that are guided by additional advances in tumor omic profiling, data interpretation and integration, and innovative clinical trial designs. The rigor with which these studies are validated and prospectively tested will determine whether and how comprehensive tumor information is incorporated into the routine care of patients. Despite the stated potential, there remain several pitfalls for the informed incorporation of omic data for clinical testing and use. A main hurdle is the risk that large-scale association data emerges without evidence-based clinical approaches for data interpretation and integration. It will be pivotal to proactively construct scientific frameworks with adequate guardrails that can prioritize tumor omic information for clinical use.


Caregivers’ role facilitating older adults’ participation in diverse health care services delivered using video telehealth  is not well-understood. This study surveyed occupational therapy (OT) practitioners across Veterans Health Administration (VHA) about caregiver participation in VA Video Connect (VVC), VHA’s videoconferencing platform. 293 OT practitioners participated in the survey, with 47% reporting that caregivers participated in VVC often. The foremost reported patient factors necessitating caregiver participation in video visits were patient lack of technical skills (76%) and cognitive impairment (72%). Barriers to caregiver participation in video visits included poor connectivity and caregivers’ own age or health related impairments, while benefits included increased collaboration with family (87%). This study enhances our understanding of caregivers’ participation in video telehealth, highlighting factors driving caregiver participation and suggesting strategies to optimize this service delivery format for older adults.