Localization of chicken parathyroid glands through vital staining.
Five, fat-soluble dyes and one, metachromatic tissue dye were administered to White Leghorn hens and broilers to determine how these compounds would color parathyroid tissue for subsequent gland localization. Sudan black, sudan red, canthaxanthin, oil red O, beta-apo-8'-carotenal, and toluidine blue O were administered orally in gelatin capsules once a day for 1, 2, or 3 days before slaughter. The dyes were administered at approximately 100 mg/dose. The carotenoid pigments were given at 200 mg/dose. Two administrations were required to develop sufficient visible staining. All dyes except the toluidine blue O were visibly deposited in the parathyroid glands. Sudan black resulted in the greatest contrast with surrounding adipose tissue. Male broilers 3 wk of age that were given one dose of sudan black showed gland definition comparable to that seen in the hens after two doses. Male broilers 5 wk of age showed less gland definition when given sudan black or sudan red for 1 or 2 days. A histological examination indicated that the fat-soluble dyes were located extracellularly. These results indicate that sudan black can be used to visually identify the parathyroid glands of chickens.


Solitary hepatic gastrinoma treated with laparoscopic radiofrequency ablation.
This is a case of a solitary hepatic gastrinoma in a 65-year-old male. The patient was diagnosed with Zollinger-Ellison syndrome in 1991. He had negative radiologic and surgical explorations at that time. He was maintained on proton-pump inhibitors for the next 10 years without symptoms. A computed tomographic (CT) scan done in April 2001 demonstrated a 5-cm right hepatic lesion. Radionucleotide scanning with octreotide demonstrated intense activity in the same area in the right hepatic lobe. His serum gastrin was 317 pg/mL. He underwent laparoscopic radiofrequency ablation of the lesion. Treatment resulted in a 6-cm ablative area giving a 1-cm margin on the tumor. One- and 3-month follow-up CT scans demonstrated adequate ablation of the tumor. An octreotide scan done 3 months postoperatively did not reveal any areas of abnormal uptake. We report success with laparoscopic radiofrequency ablation as an alternative to major hepatic resection in patients with a solitary hepatic gastrinoma.


Knowledge Among Junior Doctors About the Collection and Transport of Samples for Tuberculosis Diagnosis in a Medical College Hospital in Coastal Karnataka, India.
Background The accuracy of the TB diagnosis depends on the quality of the collected and transported samples. Inadequate knowledge and practices regarding the collection and transport of sputum samples can lead to false-negative results and delay the diagnosis and treatment of TB. This study was conducted to assess the knowledge of residents and interns about the collection and transport of sputum and other samples for the diagnosis of tuberculosis in a medical college hospital. Methods This was a cross-sectional study conducted among 120 medical interns and postgraduate residents of a medical college hospital in coastal Karnataka, India. Participants were interviewed using a pre-designed and structured questionnaire. The data was analyzed using IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp. Descriptive statistics like the mean, standard deviation, and chi-square test were used. A p-value less than 0.05 was considered statistically significant. Results Most of the study participants (76, 63.3%) belonged to the age group of 22 to 25 years and were interns. Nearly three-quarters of the participants (85, 70.8%) were female. Based on the mean score, 69.2% of the participants exhibited good knowledge. Among the socio-demographic characteristics, being a postgraduate resident was associated with good knowledge about the collection and transport of samples (p-value < 0.05). Conclusion Seven out of ten participants had good knowledge about the collection and transport of sputum and other samples for the diagnosis of tuberculosis. Strengthening the training of this category of health workers needs to be prioritized.


Potential energy surface discontinuities in local correlation methods.
We have examined the occurrence of discontinuities in bond-breaking potential energy surfaces given by local correlation methods based on the Pulay-Saebø orbital domain approach. Our analysis focuses on three prototypical dissociating systems: the C-F bond in fluoromethane, the C-C bond in singlet, ketene, and the central C-C bond in propadienone. We find that such discontinuities do not occur in cases of homolytic bond cleavage due to the inability of the Pipek-Mezey orbital localization method to separate singlet-coupled charges on distant fragments. However, for heterolytic bond cleavage, such as that observed in singlet ketene and propadienone, discontinuities occur both at stretched geometries and near equilibrium. These discontinuities are usually small, but may be of the same order of magnitude as the localization error in some cases.


Anderson-Fabry disease in children.
Although clinical evidence of major organ damage is typical of adulthood, many of the signs and symptoms of Anderson Fabry Disease (AFD) occur frequently in childhood. The clinical phenotype of AFD in pediatric patients has been described in several studies which show a higher incidence and an earlier onset of symptoms in male patients than in females. These include neurological manifestations (acroparaesthesias, chronic neuropathic pain, hypo-anhidrosis, tinnitus, hearing, loss), gastrointestinal (GI) symptoms (abdominal pain and diarrhea), angiokeratomas, ocular abnormalities (cornea verticillata, tortuous retinal vessels and subcapsular cataracts). Such manifestations may impair quality of life and, because of their unspecific nature, rarely lead to an early diagnosis. In addition, signs of major organ damage (microalbuminuria or proteinuria, urinary hyperfiltration, impaired heart rate variability, left ventricular hypertrophy, stroke) are encountered in children with AFD. Clinical trials of enzyme replacement therapy (ERT) with agalsidase alfa and agalsidase beta have been conducted in children, with clinical and pharmacodinamc effects proved by both enzyme formulations, whereas differences in safety profile and administration were found. Although several studies suggest that ERT should be started before irreversible damage in critical organs have occurred, the issue of when to initiate it has not yet been resolved. More controlled trials must be done in order to demonstrate that an early start of ERT could prevent adult complications and to assess the optimal timing of treatment in children with AFD. This review aims to provide an update of the current understanding for a better approach of pediatric AFD.


Light-Induced Thiol Oxidation of Recoverin Affects Rhodopsin Desensitization.
The excessive light illumination of mammalian retina is known to induce oxidative stress and photoreceptor cell death linked to progression of age-related macular degeneration. The photochemical damage of photoreceptors is suggested to occur via two apoptotic pathways that involve either excessive rhodopsin activation or constitutive phototransduction, depending on the light intensity. Both pathways are dramatically activated in the absence of rhodopsin desensitization by GRK1. Previously, we have shown that moderate illumination (halogen lamp, 1,500 lx, 1-5 h) of mammalian eyes provokes disulfide dimerization of recoverin, a calcium-dependent regulator of GRK1. Here, we demonstrate under in vivo conditions that both moderate long-term (metal halide lamp, 2,500 lx, 14 h, rat model) and intense short-term (halogen lamp, 30,000 lx for 3 h, rabbit model) illumination of the mammalian retina are accompanied by accumulation of disulfide dimer of recoverin. Furthermore, in the second case we reveal alternatively oxidized derivatives of the protein, apparently including its monomer with sulfinic group. Histological data indicate that thiol oxidation of recoverin precedes apoptosis of photoreceptors. Both disulfide dimer and oxidized monomer (or oxidation mimicking C39D mutant) of recoverin exhibit lowered α-helical content and thermal stability of their apo-forms, as well as increased Ca2+ affinity. Meanwhile, the oxidized monomer and C39D mutant of recoverin demonstrate impaired ability to bind photoreceptor membranes and regulate GRK1, whereas disulfide dimer exhibits notably improved membrane binding and GRK1 inhibition in absence of Ca2+. The latter effect is expected to slow down rhodopsin desensitization in the light, thereby favoring support of the light-induced oxidative stress, ultimately leading to photoreceptor apoptosis. Overall, the intensity and duration of illumination of the retina affect thiol oxidation of recoverin likely contributing to propagation of the oxidative stress and photoreceptor damage.


Identification of SERINC5-001 as the Predominant Spliced Isoform for HIV-1 Restriction.
Among the five serine incorporator (SERINC) family members, SERINC5 (Ser5) was reported to strongly inhibit HIV-1 replication, which is counteracted by Nef. Ser5 produces 5 alternatively spliced isoforms: Ser5-001 has 10 putative transmembrane domains, whereas Ser5-004, -005, -008a, and -008b do not have the last one. Here, we confirmed the strong Ser5 anti-HIV-1 activity and investigated its isoforms' expression and antiviral activities. It was found that Ser5-001 transcripts were detected at least 10-fold more than the other isoforms by real-time quantitative PCR. When Ser5-001 and its two isoforms Ser5-005 and Ser5-008a were expressed from the same mammalian expression vector, only Ser5-001 was stably expressed, whereas the others were poorly expressed due to rapid degradation. In addition, unlike the other isoforms, which are located mainly in the cytoplasm, Ser5-001 is localized primarily to the plasma membrane. To map the critical determinant, Ser5 mutants bearing C-terminal deletions were created. It was found that the 10th transmembrane domain is required for Ser5 stable expression and plasma membrane localization. As expected, only Ser5-001 strongly inhibits HIV-1 infectivity, whereas the other Ser5 isoforms and mutants that do not have the 10th transmembrane domain show very poor activity. It was also observed that the Nef counteractive activity could be easily saturated by Ser5 overexpression. Thus, we conclude that Ser5-001 is the predominant antiviral isoform that restricts HIV-1, and the 10th transmembrane domain plays a critical role in this process by regulating its protein stability and plasma membrane targeting.IMPORTANCE Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) express a small protein, Nef, to enhance viral pathogenesis in vivo Nef has an important in vitro function, which is to make virus particles more infectious, but the mechanism has been unclear. Recently, Nef was reported to counteract a novel anti-HIV host protein, SERINC5 (Ser5). Ser5 has five alternatively spliced isoforms, Ser5-001, -004, -005, -008a, and -008b, and only Ser5-001 has an extra C-terminal transmembrane domain. We now show that the Ser5-001 transcripts are produced at least 10-fold more than the others, and only Ser5-001 produces stable proteins that are targeted to the plasma membrane. Importantly, only Ser5-001 shows strong anti-HIV-1 activity. We further demonstrate that the extra transmembrane domain is required for Ser5 stable expression and plasma membrane localization. These results suggest that plasma membrane localization is required for Ser5 antiviral activity, and Ser5-001 is the predominant isoform that contributes to the activity.


MRI-GUIDED RADIOTHERAPY FOR PROSTATE CANCER: A NEW PARADIGM.
Radiotherapy is one of the key treatment modalities for primary prostate cancer. During the last decade, significant advances were made in radiotherapy technology leading to increasing both physical and biological precision. Being a loco-regional treatment approach, radiotherapy requires accurate target dose deposition while sparing surrounding healthy tissue. Conventional radiotherapy is based on computerized tomography (CT) images both for radiotherapy planning and image-guidance, however, shortcomings of CT as soft tissue imaging tool are well known. Nowadays, our ability to further escalate radiotherapy dose using hypofractionation is limited by uncertainties in CT-based image guidance and verification. Magnetic resonance imaging (MRI) is a well established imaging method for pelvic organs. In prostate cancer specifically, MRI accurately depicts prostate zonal anatomy, rectum, bladder, and pelvic floor structures with previously unseen precision owing to its sharp soft tissue contrast. The advantages of including MRI in the clinical workflow of prostate cancer radiotherapy are multifold. MRI allows for true adaptive radiotherapy to unfold based on daily MRI images taken before, during and after each radiotherapy fraction. It enables accurate dose escalation to the prostate and intraprostatic tumor lesions. Technically, MRI high-strength magnetic field and linear accelerator high energy electromagnetic beams are hardly compatible, and important efforts were made to overcome these technical challenges and integrate MRI and linear accelerator into one single treatment device, called MRI-linac. Different systems are produced by two leading vendors in the field and currently, there are around 100 MRI-linacs worldwide in clinical operations. In this narrative review paper, we discuss historical perspective of image guidance in radiotherapy, basic elements of MRI, current clinical developments in MRI-guided prostate cancer radiotherapy, and challenges associated with the use of MRI-linac in clinical practice.


Valence and salience encoding by parallel circuits from the paraventricular thalamus to the nucleus accumbens.
The anterior and posterior subregions of the paraventricular thalamus (aPVT and pPVT, respectively) play unique roles in learned behaviors, from fear conditioning to alcohol/drug intake, potentially through differentially organized projections to limbic brain regions including the nucleus accumbens medial shell (mNAcSh). Here, we found that the aPVT projects broadly to the mNAcSh and that the aPVT-mNAcSh circuit encodes positive valence, such that in vivo manipulations of the circuit modulated both innately programmed and learned behavioral responses to positively and negatively valenced stimuli, particularly in females. Further, the endogenous activity of aPVT presynaptic terminals in the mNAcSh was greater in response to positively than negatively valenced stimuli, and the probability of synaptic glutamate release from aPVT neurons in the mNAcSh was higher in females than males. In contrast, we found that the pPVT-mNAcSh circuit encodes stimulus salience regardless of valence. While pPVT-mNAcSh circuit inhibition suppressed behavioral responses in both sexes, circuit activation increased behavioral responses to stimuli only in males. Our results point to circuit-specific stimulus feature encoding by parallel PVT-mNAcSh circuits that have sex-dependent biases in organization and function.


Early combined management of frontal sinus and orbital and facial fractures.
Historically, frontal sinus fractures and associated maxillofacial fractures were addressed at different times. We retrospectively reviewed our experience with a series of 79 consecutive patients with bitable frontal sinus fractures, most with associated facial fractures, who underwent early combined cranial and maxillofacial procedures. The operations were performed emergently for patients with open or depressed skull fractures and hematomas with mass effect, and electively within 2 weeks for those with closed fractures. The cranial procedures were performed first. The nasofrontal ducts were packed with "cigars" of bacitracin powder wrapped in Surgicel. All patients received antibiotics for 2 weeks. Postoperatively, good subjective cosmetic results were obtained except in one patient. Eight patients with lumbar drains had expected temporary cerebrospinal fluid (CSF) leaks of less than 72 hours duration. Six postoperative intracranial infections (four cases of meningitis, one epidural empyema, and one intracerebral abscess) were detected; five of these occurred in patients with open depressed fractures. Patients with preoperative CSF leaks (p = 0.0039, Fisher's exact test) and open fractures (p = 0.065, Fisher's exact test) were more likely to develop intracranial infections. The combined neurosurgical and maxillofacial repairs achieved good cosmetic outcomes, with relatively low morbidity. By combining the two-stage procedure into one stage, standard surgical and anesthetic risks could potentially be reduced. Preoperative CSF leaks and open fractures were associated with a higher incidence of postoperative central nervous system infection. Early operations did not appear to be associated with a higher complication rate.


[Chapter 11. The impossible status of the embryo or the state withdrawal to the profit of vested interests].
The hesitations on the legal classification of the embryo lead to the doctrinal realization, that there is a certainty about its status, or, that it hasn't got any which allows the creator of the standard to reify it.The access to the claims which are based on specific interests seem to be at the heart of justifications to new legal rules concerning the embryo, even if It seems there are underlying specific interests.Confronted to the state disengagement in favour of these interests, the embryo, as far as French law is concerned, the embryo falls only under a limited protection which is destined to lose authority.


Rapid quantitative detection of Brucella melitensis by a label-free impedance immunosensor based on a gold nanoparticle-modified screen-printed carbon electrode.
A rapid and simple method for quantitative monitoring of Brucella melitensis using electrochemical impedance spectroscopy (EIS) is reported for the first time. The label-free immunosensors were fabricated by immobilizing Brucella melitensis antibody on the surface of gold nanoparticle-modified screen-printed carbon electrodes (GNP-SPCEs). Cyclic voltammetry (CV) and EIS were used to characterize the Brucella melitensis antigen interaction on the surface of GNP-SPCEs with antibody. A general electronic equivalent model of an electrochemical cell was introduced for interpretation of the impedance components of the system. The results showed that the change in electron-transfer resistance (Rct) was significantly different due to the binding of Brucella melitensis cells. A linear relationship between the Rct variation and logarithmic value of the cell concentration was found from 4 × 10(4) to 4 × 10(6) CFU/mL in pure culture. The label-free impedance biosensor was able to detect as low as 1 × 10(4) and 4 × 10(5) CFU/mL of Brucella melitensis in pure culture and milk samples, respectively, in less than 1.5 h. Moreover, a good selectivity versus Escherichia coli O157:H7 and Staphylococcus aureus cells was obtained for our developed immunosensor demonstrating its specificity towards only Brucella melitensis.


Hyper- and hypo- nutrition studies of the hepatic transcriptome and epigenome suggest that PPARα regulates anaerobic glycolysis.
Diet plays a crucial role in shaping human health and disease. Diets promoting obesity and insulin resistance can lead to severe metabolic diseases, while calorie-restricted (CR) diets can improve health and extend lifespan. In this work, we fed mice either a chow diet (CD), a 16 week high-fat diet (HFD), or a CR diet to compare and contrast the effects of these diets on mouse liver biology. We collected transcriptomic and epigenomic datasets from these mice using RNA-Seq and DNase-Seq. We found that both CR and HFD induce extensive transcriptional changes, in some cases altering the same genes in the same direction. We used our epigenomic data to infer transcriptional regulatory proteins bound near these genes that likely influence their expression levels. In particular, we found evidence for critical roles played by PPARα and RXRα. We used ChIP-Seq to profile the binding locations for these factors in HFD and CR livers. We found extensive binding of PPARα near genes involved in glycolysis/gluconeogenesis and uncovered a role for this factor in regulating anaerobic glycolysis. Overall, we generated extensive transcriptional and epigenomic datasets from livers of mice fed these diets and uncovered new functions and gene targets for PPARα.


A long-read sequencing and SNP haplotype-based novel preimplantation genetic testing method for female ADPKD patient with de novo PKD1 mutation.
The autosomal dominant form of polycystic kidney disease (ADPKD) is the most common hereditary disease that causes late-onset renal cyst development and end-stage renal disease. Preimplantation genetic testing for monogenic disease (PGT-M) has emerged as an effective strategy to prevent pathogenic mutation transmission rely on SNP linkage analysis between pedigree members. Yet, it remains challenging to establish reliable PGT-M methods for ADPKD cases or other monogenic diseases with de novo mutations or without a family history. Here we reported the application of long-read sequencing for direct haplotyping in a female patient with de novo PKD1 c.11,526 G > C mutation and successfully established the high-risk haplotype. Together with targeted short-read sequencing of SNPs for the couple and embryos, the carrier status for embryos was identified. A healthy baby was born without the PKD1 pathogenic mutation. Our PGT-M strategy based on long-read sequencing for direct haplotyping combined with targeted SNP haplotype can be widely applied to other monogenic disease carriers with de novo mutation.


The cell size distribution of tomato fruit can be changed by overexpression of CDKA1.
Tomato is one of the most cultivated vegetables in the world and an important ingredient of the human diet. Tomato breeders and growers face a continuous challenge of combining high quantity (production volume) with high quality (appearance, taste and perception for the consumers, processing quality for the processing industry). To improve the quality of tomato, it is important to understand the regulation of fruit development and of fruit cellular structure, which is in part determined by the sizes and numbers of cells within a tissue. The role of the cell cycle therein is poorly understood. Plant cyclin-dependent kinases (CDKs) are homologues of yeast cdc2, an important cell cycle regulator conserved throughout all eukaryotes. CDKA1 is constitutively expressed during the cell cycle and has dual functions in S- and M-phase progression. We have produced transgenic tomato plants with increased expression of CDKA1 under the control of the fruit-specific TPRP promoter, which despite a reduced number of seeds and diminished amount of jelly, developed fruits with weight and shape comparable to that of wild-type fruits. However, the phenotypic changes with regard to the pericarp thickness and placenta area were remarkable. Fruits of tomato plants with the highest expression of CDKA1 had larger septa and columella (placenta), compared with wild-type fruits. Our data demonstrate the possibility of manipulating the ratio between cell division and expansion by changing the expression of a key cell cycle regulator and probably its activity with substantial effects on structural traits of the harvested fruit.


Dissociative Motor Disorder.
Conversion disorders are more prevalent in childhood and adolescence, especially in females. They are usually associated with stressors and symptoms usually reflect a means to avoid the stressor, or also with a primary and secondary gain. This case report involves a similar situation where a young girl was treated successfully with diazepam, therapeutic nerve conduction study, and behavioral psychotherapy.


The difficult and ubiquitous problems of multiplicities.
Multiplicities are ubiquitous. They threaten every inference in every aspect of life. Despite the focus in statistics on multiplicities, statisticians underestimate their importance. One reason is that the focus is on methodology for known multiplicities. Silent multiplicities are much more important and they are insidious. Both frequentists and Bayesians have important contributions to make regarding problems of multiplicities. But neither group has an inside track. Frequentists and Bayesians working together is a promising way of making inroads into this knotty set of problems. Two experiments with identical results may well lead to very different statistical conclusions. So we will never be able to use a software package with default settings to resolve all problems of multiplicities. Every problem has unique aspects. And all problems require understanding the substantive area of application.


Identification of a novel role of T cells in postnatal vasculogenesis: characterization of endothelial progenitor cell colonies.
The colony number of early endothelial progenitor cells (EPCs) has been used as a quantitative indicator of the number of EPCs in the blood or as a biological marker of cardiovascular diseases. In the present study, we found a subset of T cells that were localized at the center of the EPC colony and played a pivotal role in colony formation and differentiation of early EPCs. We found that CD3+ CD31+ CXCR4+ T cells (referred to as angiogenic T cells in the present study) constituted the center of EPC colonies during cultures of human peripheral blood mononuclear cells. These angiogenic T cells were required for colony formation and differentiation of early EPCs. They secreted high levels of angiogenic cytokines such as vascular endothelial growth factor, interleukin-8, and matrix metalloproteinases. Angiogenic T cells showed superior angiogenic potential to the other subset of T cells in the experiments with regard to Matrigel tube formation, adhesion, transendothelial migration, and collagen invasion assay, mainly through the stromal cell-derived factor 1/CXCR-4 axis. Furthermore, angiogenic T cells enhanced endothelial cell proliferation and function. In vivo study showed that angiogenic T cells play an important role in the process of vessel formation. Clinical study showed that the level of angiogenic T cells in the peripheral blood was well correlated with EPC colony numbers and had inverse relationships with age and the number of risk factors for coronary artery disease. These findings suggest that angiogenic T cells could be a potential therapeutic target for ischemic cardiovascular diseases.


Usefulness of second 131I treatment in biochemical persistent differentiated thyroid cancer patients.
Second 131I treatment is commonly performed in clinical practice in patients with differentiated thyroid cancer and biochemical incomplete or indeterminate response (BiR/InR) after initial treatment. The objective of the is study is to evaluate the clinical impact of the second 131I treatment in BiR/InR patients and analyze the predictive factors for structural incomplete response (SiR). One hundred fifty-three BiR/InR patients after initial treatment who received a second 131I treatment were included in the study. The clinical response in a short- and medium- long-term follow-up was evaluated. After the second 131I treatment (median 8 months), 11.8% patients showed excellent response (ER), 17% SiR, while BiR/InR persisted in 71.2%. Less than half (38.5%) of SiR patients had radioiodine-avid metastases. Patients who, following the second 131I treatment, experienced SiR had larger tumor size and more frequently aggressive histology and vascular invasion than those experienced BiR/InR and ER. Also, the median values of thyroglobulin on levothyroxine therapy (LT4-Tg), Tg peak after recombinant human TSH stimulation (rhTSH-Tg) and thyroglobulin antibodies (TgAb) were significantly higher in patients who developed SiR. At last evaluation (median: 9.9 years), BiR/InR persisted in 57.5%, while 26.2% and 16.3% of the patients showed ER and SiR, respectively. About half of BiR/InR patients (71/153 (46.4%)) received further treatments after the second 131I treatment. Radioiodine-avid metastatic disease detected by the second 131I is an infrequent finding in patients with BiR/InR after initial treatment. However, specific pathologic and biochemical features allow to better identify those cases with higher probability of developing SiR, thus improving the clinical effectiveness of performing a second 131I treatment.


Acute bilateral anterior shoulder dislocation following domestic assault--case report.
A rare case of acute bilateral anterior shoulder dislocation in an elderly woman is presented. This injury resulted from domestic physical assault by her daughter inlaw. Patient defaulted after initial treatment--a common practice by patients in our society. This case is being reported to highlight the occurrence of this rare orthopaedic emergency.


Role of Albumin as a Nutritional and Prognostic Marker in Elective Intestinal Surgery.
The aim of this study was to investigate albumin, nutritional status, and inflammation in the perioperative course of patients undergoing elective intestinal surgery. A retrospective analysis of patients with preoperative measurements of nutritional parameters who underwent intestinal surgery between April 2017 and August 2018 at our institution was performed. Preoperatively, the correlation of albumin levels with markers for inflammation and nutritional status was investigated. Postoperatively, albumin levels were assessed with regard to high-grade morbidity and inflammation. A total of 105 patients were included. Preoperatively, albumin levels were correlated with both markers for nutritional status and inflammation, with phase angle (PA) (p=0.004) and C-reactive protein (CRP) (p < 0.001) as independent factors predicting the albumin levels in multivariable analysis. Postoperatively, the reduction in serum albumin (∆-albumin) on postoperative day (POD) 1/2 (p=0.025) and POD 4/5 (p=0.003) was significantly associated with Clavien-Dindo complications ≥grade III. A cut-off value of 27.3% for ∆-albumin on POD 1/2 predicted postoperative high-grade morbidity (sensitivity 75% and specificity 69%). The product of ∆-albumin and CRP on POD 4/5 identified patients with major complications more reliably than ∆-albumin or CRP alone (sensitivity 91% and specificity 72%). Preoperatively, albumin was a marker for nutritional status even if an inflammatory component was present. Postoperatively, ∆-albumin on POD 1/2 predicted high-grade morbidity. A new marker to identify patients with major complications on POD 4/5 is presented.


[Identification of concentration and brand for products using differential gel permeation chromatography].
In differential gel permeation chromatographic method (D-GPC), a standard solution and an analyzed solution are used as the eluent and injected solution, respectively. It can determine the minute differences between them. When the analyzed solution and the standard solution are identical, a null signal is given, otherwise the nonzero signal tells the detailed differences between them. Two examples, the concentration identification of five polyethylene glycol 200 (PEG200) solutions and the brand identification of three brands of beers, are given to show the application of the D-GPC method. The potential applications of the D-GPC method in quality control and the identification of counterfeit products are also discussed.


Australian vaccine preventable disease epidemiological review series: tetanus 2003-2019.
Background We examined trends in tetanus notification, hospitalisation and death data from 2003-2019 to assess the impact of adult tetanus booster recommendations in Australia. Methods Tetanus notifications and deaths from the National Notifiable Diseases Surveillance System; hospitalisations from the Australian Institute of Health and Welfare National Hospital Morbidity Database; and deaths from the Australian Coordinating Registry were analysed by age group, sex, Aboriginal and Torres Strait Islander status and state/territory. Annual rates were calculated using Australian Bureau of Statistics mid-year estimated resident populations from 2003-2019 as denominators. To assess the impact of a recommended booster dose of reduced antigen content diphtheria-tetanus-acellular pertussis (dTpa) vaccine for adults aged ≥ 65 years, notification, hospitalisation and death rates of tetanus per 100,000 population were compared pre (2003-2012) and post (2013-2019) the recommendation's introduction. Results There were 63 notifications of tetanus from 2003-2019 with an average annual incidence rate of 0.02/100,000. Similar to previous studies, the burden of tetanus in the Australian population continues to disproportionately affect the elderly, with those aged ≥ 65 years encompassing 63% (40/63) of notifications and 100% (11/11) of the deaths observed in this timeframe. Following the introduction of a recommendation for those aged ≥ 65 years to receive a dTpa booster, average annual notification and hospitalisation rates in those aged ≥ 65 years were significantly lower (notifications: 0.11/100,000 in 2003-2012 and 0.05/100,000 in 2013-2019, p = 0.01; hospitalisations: 0.24/100,000 in 2003-2012 and 0.10/100,000 in 2013-2019, p = 0.01]). The average annual death rate was similar in the two periods (0.002/100,000), although based on small numbers. Conclusions The findings of this analysis suggest a positive impact from the 2013 recommendation. However, the burden is still disproportionately higher in those aged ≥ 65 years and strategies to improve vaccination coverage in older Australians are recommended.


Physiologic occlusion vs pathologic occlusion and rationale for treatment.
Treatment concepts in dentistry are generally based on a preconceived normal state derived from clinical observation and theories rather than scientific evidence. Before treatment is proposed, the clinician should observe physiologic signs and symptoms to determine the presence of a particular pathology. This article presents different theories of occlusion, diagnostic characteristics that can be used to distinguish between physiologic occlusion and pathologic occlusion requiring treatment, and guidelines for reconstructive occlusal therapy.


Phylogenetic analysis of Pomacea canaliculata isolates collected from rice fields in different origins of China by combined mitochondrial 12S and 16S genes.
To study the genetic relationships of Pomacea canaliculata collected from rice fields in China, the mitochondrial (mt) 12S and 16S of 9 P. canaliculata isolates from 5 southern provinces in China were sequenced and analyzed. The intra-specific sequence variations of P. canaliculata were 0-1.1% for 12S and 0--0.6% for 16S, while the inter-specific variations among common Pomacea species in mt 12S and 16S were 3.0-11.7% and 2.3-10.1%, respectively. Phylogenetic analysis based on combined sequences of mt 12S and 16S revealed complex genetic structure of P. canaliculata in China. Two phylogenetic groups of P. canaliculata were indicated in China with one group sistered to P. canaliculata isolates from USA, and two groups were even found in the same province. The phylogenetic relationships of Pomacea spp. also could be effectively inferred by combined sequences of mt 12S and 16S. These findings provided basic information for further study of population genetics and diffusion pattern of P. canaliculata in China as well as in the world.


The acoustic repertoire and behavioural context of the vocalisations of a nocturnal dasyurid, the eastern quoll (Dasyurus viverrinus).
Defining an acoustic repertoire is essential to understanding vocal signalling and communicative interactions within a species. Currently, quantitative and statistical definition is lacking for the vocalisations of many dasyurids, an important group of small to medium-sized marsupials from Australasia that includes the eastern quoll (Dasyurus viverrinus), a species of conservation concern. Beyond generating a better understanding of this species' social interactions, determining an acoustic repertoire will further improve detection rates and inference of vocalisations gathered by automated bioacoustic recorders. Hence, this study investigated eastern quoll vocalisations using objective signal processing techniques to quantitatively analyse spectrograms recorded from 15 different individuals. Recordings were collected in conjunction with observations of the behaviours associated with each vocalisation to develop an acoustic-based behavioural repertoire for the species. Analysis of recordings produced a putative classification of five vocalisation types: Bark, Growl, Hiss, Cp-cp, and Chuck. These were most frequently observed during agonistic encounters between conspecifics, most likely as a graded sequence from Hisses occurring in a warning context through to Growls and finally Barks being given prior to, or during, physical confrontations between individuals. Quantitative and statistical methods were used to objectively establish the accuracy of these five putative call types. A multinomial logistic regression indicated a 97.27% correlation with the perceptual classification, demonstrating support for the five different vocalisation types. This putative classification was further supported by hierarchical cluster analysis and silhouette information that determined the optimal number of clusters to be five. Minor disparity between the objective and perceptual classifications was potentially the result of gradation between vocalisations, or subtle differences present within vocalisations not discernible to the human ear. The implication of these different vocalisations and their given context is discussed in relation to the ecology of the species and the potential application of passive acoustic monitoring techniques.


[Early functional treatment of the injured shoulder supported by an active shoulder bandage].
The following study shows the results of treatment of 29 patients suffering from rotatory cuff lesion and of 20 patients with tendinosis. The results of functional physiotherapy of the patients with rotatory cuff lesion correspond to the results of post-operative treatment described in other studies. As a result of early functional physiotherapy backed up by an active shoulder support, the treatment was both improved and shortened considerably. The accompanying pain relief achieved an earlier usability of the shoulder joint in both groups of patients. Four patients with rotatory cuff lesions were resistant to physiotherapy and finally had to undergo surgery.


Endocrine therapy-resistant breast cancer model cells are inhibited by soybean glyceollin I through Eleanor non-coding RNA.
Long-term estrogen deprivation (LTED) of an estrogen receptor (ER) α-positive breast cancer cell line recapitulates cancer cells that have acquired estrogen-independent cell proliferation and endocrine therapy resistance. Previously, we have shown that a cluster of non-coding RNAs, Eleanors (ESR1 locus enhancing and activating non-coding RNAs) formed RNA cloud and upregulated the ESR1 gene in the nuclei of LTED cells. Eleanors were inhibited by resveratrol through ER. Here we prepared another polyphenol, glyceollin I from stressed soybeans, and identified it as a major inhibitor of the Eleanor RNA cloud and ESR1 mRNA transcription. The inhibition was independent of ER, unlike one by resveratrol. This was consistent with a distinct tertiary structure of glyceollin I for ER binding. Glyceollin I preferentially inhibited the growth of LTED cells and induced apoptosis. Our results suggest that glyceollin I has a novel role in LTED cell inhibition through Eleanors. In other words, LTED cells or endocrine therapy-resistant breast cancer cells may be ready for apoptosis, which can be triggered with polyphenols both in ER-dependent and ER-independent manners.


Fabrication of optical tips from photonic crystal fibers.
We present a procedure for fabricating optical tips from photonic crystal fibers which feature a solid core surrounded by a cladding with a hexagonal, multilayer arrangement of air channels running along the length of the fiber. Such optical tips may have unique advantages for the production of near-field optical aperture probes (i.e., metal-coated optical tips with a subwavelength aperture at the tip apex). With both cladding and core made of pure silica, these fibers are fluorescence-free; they support only a single mode over a broad wavelength range (covering the visible and near-infrared spectrum), which makes them useful for multicolor experiments; and they exhibit zero group velocity dispersion at visible wavelengths, which opens up the possibility of femtosecond applications in the near field. Our tip fabrication procedure leads to a sharp, protruding, central tip formed exclusively from the fiber core amidst a regular arrangement of smaller tips from the inner, microstructured region of the cladding. A mechanism for tip formation is proposed based on optical observations at various stages, which explains the self-centering nature of the process.


Epidemiology of Asymptomatic Pre-heart Failure: a Systematic Review.
To quantify the prevalence of asymptomatic pre-heart failure (pre-HF), progression to more severe stages, and associated mortality. A systematic review was conducted between 01 January 2010 and 12 March 2020 (PROSPERO: CRD42020176141). Data of interest included prevalence, disease progression, and mortality rates. In total, 1030 sources were identified, of which, 12 reported on pre-HF (using the ACC/AHA definition for stage B HF) and were eligible. Prevalence estimates of pre-HF ranged from 11 to 42.7% (10 sources) with higher estimates found in the elderly, in patients with hypertension, and in men. Three studies reported on disease progression with follow-up ranging from 13 months to 7 years. The incidence of symptomatic HF (HF/advanced HF) ranged from 0.63 to 9.8%, and all-cause mortality from 1.6 to 5.4%. Further research is required to investigate whether early detection and intervention can slow or stop the progression from asymptomatic to symptomatic HF.


Regulating the development of pulmonary Group 2 innate lymphoid cells.
Group 2 innate lymphoid cells (ILC2s) are members of the family of innate lymphoid cells and are innately committed to type 2 immune responses. In the lungs, ILC2s are the predominant population of innate lymphoid cells (ILCs) and their development is orchestrated by several different transcription factors ensuring lineage commitment by intrinsic regulation. ILC2s are present in the lungs from the foetal period onwards and are thus exposed to extrinsic regulation due to the airways' continuous morphological changes upon birth. In this review, we will briefly summarise the dependence of ILC2s on transcription factors and discuss recently described characteristics and function of early life ILC2s in the lungs.


Simultaneous variable selection in regression analysis of multivariate interval-censored data.
Multivariate interval-censored data arise when each subject under study can potentially experience multiple events and the onset time of each event is not observed exactly but is known to lie in a certain time interval formed by adjacent examination times with changed statuses of the event. This type of incomplete and complex data structure poses a substantial challenge in practical data analysis. In addition, many potential risk factors exist in numerous studies. Thus, conducting variable selection for event-specific covariates simultaneously becomes useful in identifying important variables and assessing their effects on the events of interest. In this paper, we develop a variable selection technique for multivariate interval-censored data under a general class of semiparametric transformation frailty models. The minimum information criterion (MIC) method is embedded in the optimization step of the proposed expectation-maximization (EM) algorithm to obtain the parameter estimator. The proposed EM algorithm greatly reduces the computational burden in maximizing the observed likelihood function, and the MIC naturally avoids selecting the optimal tuning parameter as needed in many other popular penalties, making the proposed algorithm promising and reliable. The proposed method is evaluated through extensive simulation studies and illustrated by an analysis of patient data from the Aerobics Center Longitudinal Study.


The surgical anatomy of ventricular septal defects with univentricular atrioventricular connection.
Hearts that do not possess one-to-one connections at the segmental junctions almost always produce a univentricular atrioventricular connection. One ventricle is usually large and dominant and the other small, lacking one or two of its components. The ventricular septal deficiency forms part of the circulatory pathway. We take the stance that only hearts that possess a truly solitary ventricular chamber are univentricular. They cannot have a ventricular septal defect, and so are excluded from this study. This review, therefore, is concerned with the morphology of septal defects in hearts in which both atrioventricular junctions are connected exclusively to a dominant left or a dominant right ventricle, and those lacking one atrioventricular connection, where the remaining valve is connected to a dominant ventricle. This morphology in the absence of one atrioventricular connection can be modified when there is overriding of the solitary atrioventricular valve. The ventricular septal defects are analyzed and categorized for the various groups, and the position of the conduction axis is described for the well-recognized entities.


Ectopic expression of dentin sialoprotein during amelogenesis hardens bulk enamel.
Dentin sialophosphpoprotein (Dspp) is transiently expressed in the early stage of secretory ameloblasts. The secretion of ameloblast-derived Dspp is short-lived, correlates to the establishment of the dentinoenamel junction (DEJ), and is consistent with Dspp having a role in producing the specialized first-formed harder enamel adjacent to the DEJ. Crack diffusion by branching and dissipation within this specialized first-formed enamel close to the DEJ prevents catastrophic interfacial damage and tooth failure. Once Dspp is secreted, it is subjected to proteolytic cleavage that results in two distinct proteins referred to as dentin sialoprotein (Dsp) and dentin phosphoprotein (Dpp). The purpose of this study was to investigate the biological and mechanical contribution of Dsp and Dpp to enamel formation. Transgenic mice were engineered to overexpress either Dsp or Dpp in their enamel organs. The mechanical properties (hardness and toughness) of the mature enamel of transgenic mice were compared with genetically matched and age-matched nontransgenic animals. Dsp and Dpp contributions to enamel formation greatly differed. The inclusion of Dsp in bulk enamel significantly and uniformly increased enamel hardness (20%), whereas the inclusion of Dpp weakened the bulk enamel. Thus, Dsp appears to make a unique contribution to the physical properties of the DEJ. Dsp transgenic animals have been engineered with superior enamel mechanical properties.


Distributed manufacturing of an open-source tourniquet testing system.
Tourniquets are effective for casualty-prevention in emergency situations. The use of centrally-manufactured commercial tourniquets, however, is not always possible due to supply chain disruptions. The open-source hardware model has been applied to overcome these disruptions in humanitarian crises and several low-cost digitally manufacturable open-source tourniquets have been developed. With the low reliability of improvised tourniquets, it is important to ensure that distributed manufacturing of tourniquets is effective and safe. Tourniquets can be tested, but existing tourniquet testers are expensive, bulky, and complex to operate, which limits their accessibility to an even greater extent than tourniquets in extreme settings. This article fulfills a need by providing a small, transportable, open-source additive-manufactured tourniquet tester that enables inexpensive and accurate testing of tourniquets against known clinical parameters. The <$100 tourniquet tester is validated and tested for operating force of tourniquets in the field or in distributed manufacturing facilities. The tourniquet tester has a significant economic and operational advantage compared to proprietary counterparts available on the market. Once calibrated with a blood pressure monitor, the built-in LCD displays the measuring range of the tester as 0 to 200 N, which is enough to test the validation of all tourniquets.


Elucidating transmission dynamics and host-parasite-vector relationships for rodent-borne Bartonella spp. in Madagascar.
Bartonella spp. are erythrocytic bacteria transmitted via arthropod vectors, which infect a broad range of vertebrate hosts, including humans. We investigated transmission dynamics and host-parasite-vector relationships for potentially zoonotic Bartonella spp. in invasive Rattus rattus hosts and associated arthropod ectoparasites in Madagascar. We identified five distinct species of Bartonella (B. elizabethae 1, B. elizabethae 2, B. phoceensis 1, B. rattimassiliensis 1, and B. tribocorum 1) infecting R. rattus rodents and their ectoparasites. We fit standard epidemiological models to species-specific age-prevalence data for the four Bartonella spp. with sufficient data, thus quantifying age-structured force of infection. Known zoonotic agents, B. elizabethae 1 and 2, were best described by models exhibiting high forces of infection in early age class individuals and allowing for recovery from infection, while B. phoceensis 1 and B. rattimassiliensis 1 were best fit by models of lifelong infection without recovery and substantially lower forces of infection. Nested sequences of B. elizabethae 1 and 2 were recovered from rodent hosts and their Synopsyllus fonquerniei and Xenopsylla cheopsis fleas, with a particularly high prevalence in the outdoor-dwelling, highland-endemic S. fonquerniei. These findings expand on force of infection analyses to elucidate the ecological niche of the zoonotic Bartonella elizabethae complex in Madagascar, hinting at a potential vector role for S. fonquerniei. Our analyses underscore the uniqueness of such ecologies for Bartonella species, which pose a variable range of potential zoonotic threats.


Role of extracardiac factors in heart development.
Many factors extrinsic to the developing heart play important roles in determining its final form. The neural crest has been shown to provide ectomesenchyme to the pharyngeal apparatus and outflow tract, as well as the postganglionic innervation of the heart. Ablation of the neural crest providing ectomesenchyme to the outflow tract results in various cardiac malformations. These malformations have in common either outflow and/or inflow tract malalignment. Although the reason for this malalignment is not understood, it is thought that hemodynamic parameters during early cardiac morphogenesis may be disrupted causing cardiac dysmorphogenesis. The most likely area for this alteration to occur is in the pharyngeal apparatus which houses the aortic arch arteries. Various possibilities are discussed. The innervation of the heart by neural crest-derived autonomic neurons and nodose placode-derived sensory neurons is outlined, and the interactions between the two progenitive sites is discussed.


Acquired toxoplasmosis of a submandibular lymph node in a 9-year-old boy diagnosed by fine-needle aspiration cytology.
Toxoplasmosis is a parasitic infection which may be asymptomatic or produce lymphadenopathy, fever and malaise. In children the cervical lymph nodes are most commonly affected. This report describes a case of a 9-year-old boy who presented with submandibular lymphadenopathy associated with a non-vital primary tooth, which persisted following extraction of the tooth. A diagnosis of acquired toxoplasmosis was made on the findings of fine-needle aspiration cytology and subsequently confirmed by serological investigations, thus sparing the patient unnecessary hospitalization and surgery. The patient required amitryptyline as a nocturnal sedative and made a complete recovery within a few months without the need for further intervention.


The immunohistochemical expression of p21WAF1/Cip1 and Proliferating cell nuclear antigen in laryngeal squamous cell carcinomas.
The purpose of this study was to assess the significance of the expression of p21WAF1/Cip1 and proliferating cell nuclear antigen (PCNA) in human laryngeal squamous cell carcinomas. Forty-eight patients (25 supraglottic, 23 glottic) who had undergone operations between 1998 and 2003 were included in this study. The Envision immunohistochemistry method was utilized to stain these tissue specimens. The results showed that the immunostaining of p21WAF1/Cip1 do not show any correlation with differentiation, N stage, metastasis, survival, recurrence or the laryngeal site of involvement. A significant inverse correlation was detected between p21WAF1/Cip1 and the T stage. In contrast, the percentage of PCNA labelled cells showed a significant correlation with the T stage, but not with other clinicopathological parameters. There were differences in the expression of p21WAF1/Cip1 and PCNA between the supraglottic and the glottic carcinomas. In conclusion, our findings suggest that p21WAF1/Cip1 and PCNA may play an important role in the progression of carcinoma of the supraglottic larynx.


Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex.
The structural characterization of the insulin-insulin receptor (IR) interaction still lacks the conformation of the crucial B21-B30 insulin region, which must be different from that in its storage forms to ensure effective receptor binding. Here, it is shown that insulin analogues modified by natural amino acids at the TyrB26 site can represent an active form of this hormone. In particular, [AsnB26]-insulin and [GlyB26]-insulin attain a B26-turn-like conformation that differs from that in all known structures of the native hormone. It also matches the receptor interface, avoiding substantial steric clashes. This indicates that insulin may attain a B26-turn-like conformation upon IR binding. Moreover, there is an unexpected, but significant, binding specificity of the AsnB26 mutant for predominantly the metabolic B isoform of the receptor. As it is correlated with the B26 bend of the B-chain of the hormone, the structures of AsnB26 analogues may provide the first structural insight into the structural origins of differential insulin signalling through insulin receptor A and B isoforms.