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Recent advances in digital workflow have transformed clinician's ability to offer patient-specific devices for medical and dental applications. However, the digital workflow of patient-specific max...

An understudied morphosyntactic innovation, reanalysis of the Proto-Austronesian (PAn) stative intransitive prefix *ma- as a transitive affix, offers new insights into Austronesian higher-order subgrouping. Malayo-Polynesian is currently considered a primary branch of Austronesian, with no identifiably closer relationship with any linguistic subgroup in the homeland (Blust 1999, 2009/2013; Ross 2005). However, the fact that it displays the same innovative use of ma- with Amis, Siraya, Kavalan and Basay-Trobiawan and shares the merger of PAn *C/t with this group suggests that Malayo-Polynesian and East Formosan may share a common origin – the subgroup that comprises the four languages noted above. This observation points to a revised subgrouping more consistent with a socio-historical picture where the out-of-Taiwan population descended from a seafaring community expanding to the Batanes and Luzon after having developed a seafaring tradition. It also aligns with recent findings in archaeology and genetics that (i) eastern Taiwan is the most likely starting point of Austronesian dispersal (Hung 2005, 2008, 2019; Bellwood 2017; Bellwood & Dizon 2008; Carson & Hung 2018) and (ii) that the Amis bear a significantly closer relationship with Austronesian communities outside Taiwan (Capelli et al. 2001; Trejaut et al. 2005; McColl et al. 2018; Pugach et al. 2021; Tätte et al. 2021). Future investigation of additional shared innovations between Malayo-Polynesian and East Formosan could shed further light on their interrelationships.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease. We previously identified fibrogenic mesenchymal progenitor cells (MPCs) in the lungs of patients with IPF who serve as drivers of progressive fibrosis. Recent single-cell RNA sequencing work revealed that IPF MPCs with the highest transcriptomic network entropy differ the most from control MPCs and that increased CD44 was a marker of these IPF MPCs. We hypothesize that IPF MPCs with high CD44 (CD44hi) expression will display enhanced fibrogenicity. We demonstrate that CD44-expressing MPCs are present at the periphery of the IPF fibroblastic focus, placing them in regions of active fibrogenesis. In a humanized mouse xenograft model, CD44hi IPF MPCs are more fibrogenic than CD44lo IPF MPCs, and knockdown of CD44 diminishes their fibrogenicity. CD44hi IPF MPCs display increased expression of pluripotency markers and enhanced self-renewal compared with CD44lo IPF MPCs, properties potentiated by IL-8. The mechanism involves the accumulation of CD44 within the nucleus, where it associates with the chromatin modulator protein Brahma-related gene 1 (Brg1) and the zinc finger E-box binding homeobox 1 (Zeb1) transcription factor. This CD44/Brg1/Zeb1 nuclear protein complex targets the Sox2 gene, promoting its upregulation and self-renewal. Our data implicate CD44 interaction with the epigenetic modulator protein Brg1 in conveying IPF MPCs with cell-autonomous fibrogenicity.

A number of states, starting with California, have recently removed all non-medical exemptions from their laws requiring vaccinations for schoolchildren. California was also one of the earliest states to include a broad non-medical, or personal, belief exemption in its modern immunization law, which it did with a 1961 law mandating polio vaccination for school enrollment, Assembly Bill 1940 (AB 1940). This paper examines the history of AB 1940’s exemption clause as a case study for shedding light on the little-examined history of the personal belief exemption to vaccination in the United States. This history shows that secular belief exemptions date back further than scholars have allowed. It demonstrates that such exemptions resulted from political negotiation critical to ensuring compulsory vaccination’s political success. It challenges a historiography in which antivaccination groups and their allies led late-nineteenth and early-twentieth century opposition to vaccination mandates while religious groups drove mid-twentieth century opposition. It also complicates the historiographic idea of a return to compulsion in the late 1960s, instead dating this return a decade earlier, to a time when belief exemptions in polio vaccination mandates helped reconcile the goal of a widely vaccinated population with the sacrosanct idea of health as a personal responsibility.

Summary Objective The pathophysiology of sudden unexpected death in epilepsy (SUDEP) remains undetermined. Seizures are accompanied by respiratory dysfunction (RD). Postictal generalized electroencephalography (EEG) suppression (PGES) may follow generalized tonic–clonic seizures (GTCS). Following GTCS patients have impaired arousal and may be motionless. Patients with SUDEP are usually prone. Postictal immobility (PI) may contribute to SUDEP by not permitting repositioning of the head to allow unimpeded ventilation. To determine whether RD and/or ictal characteristics are associated with PI, we analyzed patients with GTCS in the epilepsy monitoring unit. Method We investigated for associations between PI duration and PGES, ictal/postictal oxygen saturation (SpO2), end-tidal CO2 (ETCO2), seizure localization, duration, and tonic and total convulsive phase duration. We investigated for linkage between PGES and these measures. Results Seventy patients with 181 GTCS and available SpO2 and/or ETCO2 data were studied. Simple linear regression analysis by seizures showed that PI duration was associated with peak periictal ETCO2 (p = 0.03), duration of oxygen desaturation (p = 0.005) and with SpO2 nadir (p = 0.02). PI duration was not associated with tonic, convulsive phase or total seizure duration. Analysis by patients also showed significant association of PI with RD. Duration of PI was longer following seizures with PGES (p

The mechanical properties of the soft palate can be associated with breathing abnormalities. Dorsal displacement of the soft palate (DDSP) is a naturally occurring equine soft palate disorder caused by displacement of the caudal edge of the soft palate. Snoring and a more serious, sometimes life-threatening, condition called obstructive sleep apnea (OSA) are forms of sleep-related breathing disorders in humans which may involve the soft palate. The goal of this study was to investigate the effect of injecting the protein crosslinker genipin into the soft palate to modify its mechanical properties for the treatment of equine DDSP with potential implications for the treatment of snoring and OSA in humans. Ex vivo experiments consisted of mechanical testing and a wind tunnel study to examine the effect of genipin on the mechanical properties, displacement, and vibration of equine soft palates. A pilot in vivo study was completed using DDSP and control horses to test the safety and effectiveness of injecting a genipin reagent into the soft palate. The wind tunnel testing demonstrated a greater than 50% decrease in transient deformation and a greater than 33% decrease in steady-state vibrations for all doses of genipin tested. Ultimate tensile stress, yield stress, and Young’s modulus were higher in the genipin-treated distal soft palate specimens by 52%, 53%, and 63%, respectively. The pilot in vivo study showed a reduction of snoring loudness in all DDSP horses and elimination of DDSP in at least one of three horses. The difficulty of using a 1-meter-long endoscopic injection needle contributed to a consistent overinjection of the equine soft palates, causing excessive stretching (pillowing) and related degradation of the tissue. These ex vivo and in vivo results demonstrated reduced vibration amplitude and flaccidity and increased strength of genipin-treated soft palates, suggesting that genipin crosslinking could become an effective and safe treatment for soft palate related breathing abnormalities.

Nociceptive information is modulated by a large number of endogenous signaling agents that change over the course of recovery from injury. This plasticity makes understanding regulatory mechanisms involved in descending inhibition of pain scientifically and clinically important. Neurons that synthesize the neuropeptide TIP39 project to many areas that modulate nociceptive information. These areas are enriched in its receptor, the parathyroid hormone 2 receptor (PTH2R). We previously found that TIP39 affects several acute nociceptive responses, leading us to now investigate its potential role in chronic pain. Following nerve injury, both PTH2R and TIP39 knockout mice developed less tactile and thermal hypersensitivity than controls and returned to baseline sensory thresholds faster. Effects of hindpaw inflammatory injury were similarly decreased in knockout mice. Blockade of α-2 adrenergic receptors increased the tactile and thermal sensitivity of apparently recovered knockout mice, returning it to levels of neuropathic controls. Mice with locus coeruleus (LC) area injection of lentivirus encoding a secreted PTH2R antagonist had a rapid, α-2 reversible, apparent recovery from neuropathic injury similar to the knockout mice. Ablation of LC area glutamatergic neurons led to local PTH2R-ir loss, and barley lectin was transferred from local glutamatergic neurons to GABA interneurons that surround the LC. These results suggest that TIP39 signaling modulates sensory thresholds via effects on glutamatergic transmission to brainstem GABAergic interneurons that innervate noradrenergic neurons. TIP39’s normal role may be to inhibit release of hypoalgesic amounts of norepinephrine during chronic pain. The neuropeptide may help maintain central sensitization, which could serve to enhance guarding behavior.

To examine the clinical significance of persistent renal enhancement after iodixanol administration.We retrospectively studied 166 consecutive patients who underwent non-enhanced abdominopelvic CT within 7 days after receiving intra-arterial (n=99) or intravenous (n=67) iodixanol. Renal attenuation was measured for each non-enhanced CT scan. Persistent renal enhancement was defined as CT attenuation55 Hounsfield units (HU). Contrast-induced nephropathy (CIN) was defined as a rise in serum creatinine0.5 mg/dL within 5 days after contrast administration.While the intensity and frequency of persistent renal enhancement was higher after intra-arterial (mean CT attenuation of 73.7 HU, seen in 54 of 99 patients, or 55%) than intravenous contrast material administration (51.8 HU, seen in 21 of 67, or 31%, p0.005), a multivariate regression model showed that the independent predictors of persistent renal enhancement were a shorter time interval until the subsequent non-enhanced CT (p0.001); higher contrast dose (p0.001); higher baseline serum creatinine (p0.01); and older age (p0.05). The route of contrast administration was not a predictor of persistent renal enhancement in this model. Contrast-induced nephropathy was noted in 9 patients who received intra-arterial (9%) versus 3 who received intravenous iodixanol (4%), and was more common in patients with persistent renal enhancement (p0.01).Persistent renal enhancement at follow-up non-contrast CT suggests a greater risk for contrast-induced nephropathy, but the increased frequency of striking renal enhancement in patients who received intra-arterial rather than intravenous contrast material also reflects the larger doses of contrast and shorter time to subsequent follow-up CT scanning for such patients.

OBJECTIVE. In this article, we consider a multitude of the latest techniques used for evaluating benign and malignant pulmonary diseases. Our review will include mostly clinically pertinent studies, but we have also included breakthrough basic science research that has potentially significant clinical implications. CONCLUSION. Molecular imaging enables noninvasive visualization and measurement of the dynamic molecular processes within living organisms. Early recognition of molecular and cellular malfunctions can help optimize diagnostic and therapeutic strategies.

The parathyroid hormone 2 (PTH2) receptor is a Family B G-protein coupled receptor most highly expressed within the brain. Current evidence suggests that tuberoinfundibular peptide of 39 residues (TIP39) is the PTH2 receptor's endogenous ligand. To facilitate investigation of the physiological function of the PTH2 receptor/TIP39 system, we have developed a novel PTH2 receptor antagonist, by changing several residues within the amino terminal domain of TIP39. Histidine4, tyrosine5, tryptophan6, histidine7-TIP39 binds the PTH2 receptor with high affinity, has over 30-fold selectivity for the rat PTH2 receptor over the rat PTH1 receptor and displays no detectable agonist activity. This ligand should be useful for in vivo investigation of PTH2 receptor function.

Fear-related psychopathologies such as post-traumatic stress disorder are characterized by impaired extinction of fearful memories. Recent behavioral evidence suggests that the neuropeptide tuberoinfundibular peptide of 39 residues (TIP39), via its receptor, the parathyroid hormone 2 receptor (PTH2R), modulates fear memory. Here we examined the anatomical and cellular localization of TIP39 signaling that contributes to the increase in fear memory over time following a traumatic event, called fear memory incubation. Contextual freezing, a behavioral sign of fear memory, was significantly greater in PTH2R knock-out than wild-type male mice 2 and 4 weeks after a 2 s 1.5 mA footshock. PTH2R knock-out mice had significantly reduced c-Fos activation in the medial amygdala (MeA) following both footshock and fear recall, but had normal activation in the hypothalamic paraventricular nucleus and the amygdalar central nucleus compared with wild-type. We therefore investigated the contribution of MeA TIP39 signaling to fear incubation. Similar to the effect of global TIP39 signaling loss, blockade of TIP39 signaling in the MeA by lentivirus-mediated expression of a secreted PTH2R antagonist augmented fear incubation. Ablation of MeA PTH2R-expressing neurons also strengthened the fear incubation effect. Using the designer receptor exclusively activated by designer drug pharmacogenetic approach, transient inhibition of MeA PTH2R-expressing neurons before or immediately after the footshock, but not at the time of fear recall, enhanced fear incubation. Collectively, the findings demonstrate that TIP39 signaling within the MeA at the time of an aversive event regulates the increase over time in fear associated with the event context.SIGNIFICANCE STATEMENTFear-related psychopathologies such as post-traumatic stress disorder (PTSD) are characterized by excessive responses to trauma-associated cues. Fear responses can increase over time without additional cue exposure or stress. This work shows that modulatory processes within the medial nucleus of the amygdala near the time of a traumatic event influence the strength of fear responses that occur much later. The modulatory processes include signaling by the neuropeptide TIP39 and neurons that express its receptor. These findings will help in the understanding of why traumatic events sometimes have severe psychological consequences. One implication is that targeting neuromodulation in the medial amygdala could potentially help prevent development of PTSD.

A 52-year-old male was subjected to an F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) study for the evaluation of newly diagnosed non-Hodgkin′s lymphoma. An incidental non-FDG avid urinary bladder mass was detected, as well as an absent kidney. Ureterocele was suspected, but subsequently a seminal vesicle cyst was confirmed on a CT urogram.

The soybean [Glycine max (L.) Merr.] expressed sequence tagged (EST) database is growing rapidly and promises to be a valuable resource for discovering agronomically important genes. Genetic maps featuring cDNA clones of known sequence and functiona re important because association of genes with phenotypes will increase understanding of the molecular mechanisms affecting valuable agronomic traits. Our objective is to place sequenced cDNA (EST) and genomic clones on an anchored soybean genetic map. The genetic mapping of these markers was conducted by standard restriction fragment length polymorphism (RFLP) techniques with an F 2 population of 149 individuals derived from a cross between two publicly available soybean genotypes cv. Noir I (PI 290136) and BARC-2 (Rj 4 ) (PI 547895). DNA sequences of mapped EST and genomic clones were compared with accessions in GenBank, and significant sequence similarities are reported. The ESTs were more likely than the genomic clones to have a significant similarity to a GenBank accession. Because the objective was to map ESTs and sequenced genomic clones, only the 24 linkage groups (1200 cM) containing the 39 mapped EST and sequenced genomic clone markers plus the four phenotypic traits root fluorescence (Fr 2 ), seed coat color (I), flower color (W 1 ) and nodulation response (Rj 4 ) were presented. Amplified fragment length polymorphism (AFLP) and random amplified polymorphic DNA (RAPD) markers were added to increase marker density. Simple sequence repeat (SSR) markers were included to align this map with other soybean maps. The population has been further advanced to develop a F 8:2 recombinant inbred line population available to researchers interested in associating the mapped cDNAs with quantitatively inherited traits.

We investigated the application of the PCR-based fingerprinting technique, amplified fragment length polymorphism (AFLP), in orchids. The optimal AFLP patterns have been determined using primer combinations of EcoRI +4 and MseI +3 selective nucleotides. The same reproducible AFLP patterns were demonstrated in genomic DNAs isolated both from: (1) different orchid tissues, e.g. leaves and flowers; and (2) orchid flowers collected at different times. Genomic variations among different cultivars of vandaceous orchid hybrids were successfully determined by AFLP analysis. More than 10% of the AFLP bands were polymorphic DNA when siblings, derived from the same original crosses (two cultivars of Aranda Christine, five cultivars of Mokara Willie How), were used. Only 0.3–0.7% of the AFLP patterns were shown to be polymorphic when different cultivars, originating from somatic mutations during meristem culture for massive propagation, were used (two cultivars of Ar. Christine, four cultivars of M. Chark Kuan).

Three different DNA mapping techniques—RFLP, RAPD and AFLP—were used on identical soybean germplasm to compare their ability to identify markers in the development of a genetic linkage map. Polymorphisms present in fourteen different soybean cultivars were demonstrated using all three techniques. AFLP, a novel PCR-based technique, was able to identify multiple polymorphic bands in a denaturing gel using 60 of 64 primer pairs tested. AFLP relies on primers designed in part on sequences for endonuclease restriction sites and on three selective nucleotides. The 60 diagnostic primer pairs tested for AFLP analysis each distinguished on average six polymorphic bands. Using specific primers designed for soybean fromEco RI andMse I restriction site sequences and three selective nucleotides, as many as 12 polymorphic bands per primer could be obtained with AFLP techniques. Only 35% of the RAPD reactions identified a polymorphic band using the same soybean cultivars, and in those positive reactions, typically only one or two polymorphic bands per gel were found. Identification of polymorphic bands using RFLP techniques was the most cumbersome, because Southern blotting and probe hybridization were required. Over 50% of the soybean RFLP probes examined failed to distinguish even a single polymorphic band, and the RFLP probes that did distinguish polymorphic bands seldom identified more than one polymorphic band. We conclude that, among the three techniques tested, AFLP is the most useful.

The inhibition of bacterial growth by carbenicillin and cefotaxime was demonstrated using three different Agrobacterium tumefaciens strains, LBA4404, C58 and EHA101. LBA4404 was the most sensitive strain to carbenicillin and cefotaxime. Significantly toxic effects were observed when tobacco leaf explants were grown on MS medium containing 250 μg/ml carbenicillin and 1 μg/ml 2,4-dichlorophenoxyacetic acid (2,4-D). The regeneration of tobacco shoots from tobacco leaf explants was decreased as the addition of carbenicillin increased from 250 μg/ml to 2000 μg/ml in MS medium containing 0.5 μg/ml of 6-benzylaminopurine (BA). Interestingly, tobacco leaf explants grown on the MS medium containing carbenicillin alone up to 1000 μg/ml did not show any toxic effects. Moreover, chemical structure comparisons revealed that carbenicillin contains auxin related structures like 2,4-D or α-naphthalenacetic acid (NAA), suggesting that the toxic effects of combinations of carbenicillin and 2,4-D may be due to high auxin activity levels. Further studies demonstrated that by adjusting the levels of carbenicillin and 2,4-D, the transformation efficiency of Arabidopsis thaliana ecotype Columbia and Landsberg was significantly improved from 20% to >90% using Agrobacterium-mediated transformation.

Particle disease is a loss of bone that commonly occurs about five years after arthroplasty. The cause is secondary to microabrasive wear and shedding of any portion of the prosthesis, and the microscopic foreign bodies activate inflammation which can lead to pain. This report describes the imaging findings of an 80-year-old female with particle disease detected with 18F-fluoride PET/CT.

Purpose: Gastric emptying scintigraphy (GES) is the gold standard for diagnosing gastroparesis. We retrospectively investigate the largest number of GES at a single institute using the classic protocol. The gastric emptying half-time (T 50 ) is evaluated with factors that may alter the half-time. Method: 515 solid GES were compared with the patient’s medical history, drugs used before exam, gender, body mass index (BMI) at the time of exam, indication for the exam, and age. After consumption of Technetium-99m albumin colloid, anterior and posterior images were acquired in 15 minutes intervals for at least 90 minutes. The half-time was linearly or exponentially interpolated on the basis of multiple data points using software. Results : The average normal T 50 was 72.8 minutes ± 50.2 minutes. T 50 increased in patients with a medical history of diabetes (p < 0.042), hiatal hernia, gastrointestinal obstruction, esophagitis, use of narcotic (p < 0.003), and a BMI under 18.5. It did not have any correlation with gender. T 50 decreased with increasing age or use of metoclopramide (p < 0.0005). Conclusion: GES is an important diagnostic step that leads to the correct treatment. T 50 is an easy and objective value for diagnosing gastroparesis. It is associated with many diseases that nuclear physicians and radiologists should be aware of.

Nonradioactive amplified fragment-length polymorphism (AFLP) marker detection, a PCR-based, DNA-fingerprinting technique, was achieved by blotting AFLP products after electrophoresis onto a nylon membrane and subsequently hybridizing the blot with an alkaline phosphatase-labeled AFLP probe. Similar AFLP profiles were obtained by both a nonradioactive, chemiluminescent detection technique and by conventional AFLP marker detection using 32P-labeled AFLP primers. The suitability of the method using different gel systems combined with subsequent chemiluminescent detection of AFLP markers is validated by similar dendrograms that were generated using the unweighted pair group method with arithmetic averages (UPGMA). Moreover, chemiluminescent detection of AFLP markers using a universal AFLP nonradioactive probe has been successfully applied on prokaryotes such as Agrobacterium and eukaryotic genomes such as soybean and fungi.

Amplified restriction fragment polymorphism (AFLP) is a PCR-based DNA fingerprinting technique. In AFLP analysis, bacterial genomic DNA is digested with restriction enzymes, ligated to adapters, and a subset of DNA fragments are amplified using primers containing 16 adapter defined sequences with one additional arbitrary nucleotide. Polymorphisms of different Escherichia coli strains or Agrobacterium tumefaciens strains were demonstrated as distinct, unique bands in a denaturing sequencing gel using AFLP. The polymorphisms detected between BL21 and BL21F'IQ and between DH5 alpha and DH5 alpha F'IQ strains indicated that AFLP is able to resolve differences in F' episomal DNA (approximately 100 kb).

cDNA sequences are important for defining the coding region of genes, and full-length cDNA clones have proven to be useful for investigation of the function of gene products. We produced cDNA libraries containing 3.5-5 x 10(5) primary transformants, starting with 5 mug of total RNA prepared from mouse pituitary, adrenal, thymus, and pineal tissue, using a vector-primed cDNA synthesis method. Of approximately 1000 clones sequenced, approximately 20% contained the full open reading frames (ORFs) of known transcripts, based on the presence of the initiating methionine residue codon. The libraries were complex, with 94, 91, 83 and 55% of the clones from the thymus, adrenal, pineal and pituitary libraries, respectively, represented only once. Twenty-five full-length clones, not yet represented in the Mammalian Gene Collection, were identified. Thus, we have produced useful cDNA libraries for the isolation of full-length cDNA clones that are not yet available in the public domain, and demonstrated the utility of a simple method for making high-quality libraries from small amounts of starting material.