Expression and functional role of peroxisome proliferator-activated receptor-gamma in ovarian folliculogenesis in the sheep.
Peroxisome proliferator-activated receptor (PPARgamma) is a nuclear receptor that is activated by fatty acids and derivatives and the antidiabetic glitazones, which plays a role in the control of lipid and glucose homeostasis. In the present work, we tested the hypothesis that PPARgamma plays a role in reproductive tissues by studying its expression and function in the hypothalamo-pituitary-ovary axis in the sheep. PPARgamma 1 and PPARgamma 2 proteins and mRNAs were detected in whole ovine pituitary and ovary but not in hypothalamic extracts. In situ hybridization on ovarian section localized PPARgamma mRNA in the granulosa layer of follicles. Interestingly, PPARgamma expression was higher in small antral (1-3 mm diameter) than in preovulatory follicles (>5 mm diameter) (P < 0.001) and was not correlated with healthy status. To assess the biological activity of ovarian PPARgamma, ovine granulosa cells were transfected with a reporter construct driven by PPARgamma-responsive elements. Addition of rosiglitazone, a PPARgamma ligand, stimulated reporter gene expression, showing that endogenous PPARgamma is functional in ovine granulosa cells in vitro. Moreover, rosiglitazone inhibited granulosa cell proliferation (P < 0.05) and increased the secretion of progesterone in vitro (P < 0.05). This stimulation effect was stronger in granulosa cells from small than from large follicles. In contrast, rosiglitazone had no effect on LH, FSH, prolactin and growth hormone secretion by ovine pituitary cells in vitro. Overall, these data suggest that PPARgamma ligands might stimulate follicular differentiation in vivo likely through a direct action on granulosa cells rather than by modulating pituitary hormone secretion.


In silico analysis for factors affecting anti-malarial penetration into red blood cells.
Malaria is a parasitic disease that produces significant infection in red blood cells. The objective of this study is to investigate the relationships between factors affecting the penetration of currently available anti-malarials into red blood cells. Fifteen anti-malarial drugs listed in the third edition of the World Health Organization malaria treatment guidelines were enrolled in the study. Relationship analysis began with the prioritization of the physicochemical properties of the anti-malarials to create a multivariate linear regression model that correlates the red blood cell penetration. It was found that protein binding was significantly correlated with red blood cell penetration, with a negative coefficient. The next step was repeated analysis to find molecular descriptors that influence protein binding. The coefficients of the number of rotating bonds and the number of aliphatic hydrocarbons are negative, as opposed to the positive coefficients of the number of hydrogen bonds and the number of aromatic hydrocarbons. The p-value was less than 0.05. Anti-malarials with a small number of hydrogen bonds and aromatic hydrocarbons, together with a high number of rotatable bonds and aliphatic hydrocarbons, may have a higher tendency to penetrate the red blood cells.


Monolithic, 3D-printed lab-on-disc platform for multiplexed molecular detection of SARS-CoV-2.
Multiplexed detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rather than detection targeting a single gene is crucial to ensure more accurate coronavirus disease 2019 (COVID-19) diagnostics. Here, we develop a monolithic, 3D-printed, lab-on-disc platform for multiplexed molecular detection of SARS-CoV-2. The centrifugal lab-on-disc is fabricated in one step using simple 3D printing technology, circumventing the need for aligning and binding multiple layers. By combining isothermal amplification technology, this lab-on-disc platform is capable of simultaneously detecting the nucleoprotein and envelope genes of SARS-CoV-2 as well as an internal control of the human POP7 gene. Within a 50-minute incubation period, 100 copies SARS-CoV-2 RNA can be detected through visual observation according to color and fluorescence changes in the disc. Further, we clinically validated the lab-on-disc platform by testing 20 nasopharyngeal swab samples and demonstrated a sensitivity of 100% and an accuracy of 95%. Therefore, the monolithic, 3D-printed, lab-on-disc platform provides simple, rapid, disposable, sensitive, reliable, and multiplexed molecular detection of SARS-CoV-2, holding promise for COVID-19 diagnostics at the point of care.


Medicalethnobotany of some weeds of Mauritius and Rodrigues.
The people of Mauritius and Rodrigues have always used medicinal plants for various ailments, and have for a long time been dependent on surrounding plant resources for their food, shelter, fodder, health care and other cultural purposes. However, encroaching industrialization and the accompanying changes in their lifestyles are responsible for the decrease of practice in the local use of plants for medicine. It is, therefore, felt worthwhile to record the native uses of these plants before the information is lost. The present paper deals with the medicalethnobotany of 53 genera and 94 different species of plants considered as weeds.


Suitable but requiring support: How the midwifery model of care offers opportunities to counsel the vaccine hesitant pregnant population.
Uptake of vaccination during pregnancy in Canada is lower than comparator countries. A recommendation from a trusted perinatal healthcare provider is a key opportunity to promote vaccine uptake and improve confidence. This study aims to identify barriers and opportunities to vaccination in midwifery care. Seventeen semi-structured telephone interviews with practicing midwives, educators and public health professionals with immunization training experiences were conducted. Documents pertaining to the midwifery profession (approx. 50) were reviewed. Inductive thematic analysis identified logistical, interprofessional, and information barriers preventing Canadian midwives from administering vaccines and counseling clients about vaccination, as well as opportunities to address each barrier. Key interventions at the level of logistics, training, and client information materials would help address barriers to the integration of midwives into the provision and recommendation of vaccines in perinatal care across Canada.


Highly selective and sensitive ratiometric fluorescent polymer dots for detecting hypochlorite in 100% aqueous media.
Hypochlorite (ClO-), as a momentous reactive oxygen species (ROS), is highly desirable due to it associated with a number of human diseases. Therefore, the development of simple and convenient water-soluble ratiometric fluorescent probes is of great significance. In this work, water-soluble ratiometric fluorescent polymer dots (FPDs) for detecting ClO- were prepared via incorporation of reversible addition-fragmentation chain transfer radical polymerization (RAFT), grafting technique and coprecipitation strategy. Upon the addition of ClO-, due to the intramolecular heavy atom effect (HAE) by chlorine (Cl), the fluorescence of fluorescein units in FPDs was significantly quenched, while another reference fluorophore (P2) in FPDs keeps constant. Furthermore, the FPDs exhibited excellent sensitivity (detection limit: 2.2 nM) and selectivity, good water-solubility. In addition, FPDs was successfully utilized to detect ClO- in tap water and drink water. It implies that the nanoprobes have the great potential applications in biological sensing and imaging.


Significance of both alkB and P450 alkane-degrading systems in Tsukamurella tyrosinosolvens: proteomic evidence.
The Tsukamurella tyrosinosolvens PS2 strain was isolated from hydrocarbons-contaminated petrochemical sludge as a long chain alkane-utilizing bacteria. Complete genome analysis showed the presence of two alkane oxidation systems: alkane 1-monooxygenase (alkB) and cytochrome P450 monooxygenase (P450) genes with established high homology to the well-known alkane-degrading actinobacteria. According to the comparative genome analysis, both systems have a wide distribution among environmental and clinical isolates of the genus Tsukamurella and other members of Actinobacteria. We compared the expression of different proteins during the growth of Tsukamurella on sucrose and on hexadecane. Both alkane monooxygenases were upregulated on hexadecane: AlkB-up to 2.5 times, P450-up to 276 times. All proteins of the hexadecane oxidation pathway to acetyl-CoA were also upregulated. Accompanying proteins for alkane degradation involved in biosurfactant synthesis and transport of organic and inorganic molecules were increased. The change in the carbon source affected the pathways for the regulation of translation and transcription. The proteomic profile showed that hexadecane is an adverse factor causing activation of general and universal stress proteins as well as shock and resistance proteins. Differently expressed proteins of Tsukamurella tyrosinosolvens PS2 shed light on the alkane degradation in other members of Actinobacteria class. KEY POINTS: • alkB and P450 systems have a wide distribution among the genus Tsukamurella. • alkB and P450 systems have coexpression with the predominant role of P450 protein. • Hexadecane causes significant changes in bacterial proteome.


Importance of regional PM2.5 transport and precipitation washout in heavy air pollution in the Twain-Hu Basin over Central China: Observational analysis and WRF-Chem simulation.
With observational analysis and WRF-Chem simulation on a heavy air pollution event in January 2019 over the Twain-Hu Basin (THB) in Central China, this study characterized the regional transport of PM2.5 emitted from the North China Plain (NCP) to the THB region in Central China and quantitatively assessed the influence of the regional PM2.5 transport and precipitation washout on PM2.5 change in the wintertime heavy air pollution over the THB. It was found that the THB's heavy air pollution event was exacerbated by the strong northeasterly winds driving a quasi 2-day time lag of regional PM2.5 transport from the NCP to the THB. The multi-scale atmospheric circulations of cold air invasion influenced by East Asian winter monsoon and the terrain block of THB altered the structures of regional PM2.5 transport in deteriorating air quality to the THB. It was assessed for the THB region that the enhancing contribution of regional PM2.5 transport to the high air pollution level reached up to 70.5% in the heavy air pollution, and the precipitation washout could contribute the 55.3% PM2.5 removal to dissipating the PM2.5 pollution over the THB with frequent precipitation and wet environment, distinguishing from the dominance of wind-cleaning air pollution in the other regions in China.


Beat-to-beat Ca(2+)-dependent regulation of sinoatrial nodal pacemaker cell rate and rhythm.
Whether intracellular Ca(2+) regulates sinoatrial node cell (SANC) action potential (AP) firing rate on a beat-to-beat basis is controversial. To directly test the hypothesis of beat-to-beat intracellular Ca(2+) regulation of the rate and rhythm of SANC we loaded single isolated SANC with a caged Ca(2+) buffer, NP-EGTA, and simultaneously recorded membrane potential and intracellular Ca(2+). Prior to introduction of the caged Ca(2+) buffer, spontaneous local Ca(2+) releases (LCRs) during diastolic depolarization were tightly coupled to rhythmic APs (r²=0.9). The buffer markedly prolonged the decay time (T₅₀) and moderately reduced the amplitude of the AP-induced Ca(2+) transient and partially depleted the SR load, suppressed spontaneous diastolic LCRs and uncoupled them from AP generation, and caused AP firing to become markedly slower and dysrhythmic. When Ca(2+) was acutely released from the caged compound by flash photolysis, intracellular Ca(2+) dynamics were acutely restored and rhythmic APs resumed immediately at a normal rate. After a few rhythmic cycles, however, these effects of the flash waned as interference with Ca(2+) dynamics by the caged buffer was reestablished. Our results directly support the hypothesis that intracellular Ca(2+) regulates normal SANC automaticity on a beat-to-beat basis.


Validity of autorefraction after cataract surgery with multifocal ReZoom intraocular lens implantation.
To evaluate the clinical utility of spherocylindrical automated refraction (AR) compared with subjective manifest refraction (MR) after cataract surgery with implantation of ReZoom refractive multifocal intraocular lenses (IOLs) (Advanced Medical Optics, Inc.). Private Practice. This prospective nonrandomized interventional study consisted of 72 patients with bilateral cataract and a potential visual acuity of at least 20/40. Patients had bilateral nonsimultaneous cataract surgery and implantation of a ReZoom IOL. Manifest refraction was performed in all patients followed by 3 consecutive measurements using the Topcon KR-8000 autorefractor with nondilated and dilated pupils. Assessment of repeatability of multiple consecutive ARs and comparison of the AR and MR using power vector analysis were performed at the 6-month follow-up. The main outcome measures were the correlation between AR and MR with sphere, spherical equivalent, and astigmatism as well as the repeatability of AR before and after dilation with phenylephrine 10%. Repeatability analysis showed that the initial nondilated AR was not significantly different from the mean of the 3 refractions for nondilated and dilated measurements. The mean difference between the initial AR and the MR was -0.84 +/- 0.62 diopters (D) for sphere (SD), -1.00 +/- 0.61 D for spherical equivalent, and -0.06 +/- 0.19 D and -0.01 +/- 0.17 D, respectively, for J(0) and J(45), the 2 components of astigmatism. Linear regression of AR versus MR data showed poor correlation for sphere (R(2) = 0.4852) and spherical equivalent (R(2) = 0.5529), whereas the correlation for the 2 astigmatic components of vector analysis was excellent (J(0), R(2) = 0.8881; J(45), R(2) = 0.8640). Correlation was better when the MR residual refractive defect was higher. Although autorefraction showed excellent agreement with subjective refractive astigmatism, correlation with spherical values was poor, with a trend toward more negative values. Autorefraction after ReZoom IOL implantation can be used as a good starting point for subjective refraction of astigmatism; however, spherical values should be underestimated.


Effects of biochar supported nano zero-valent iron with different carbon/iron ratios on two-phase anaerobic digestion of food waste.
The promotion effects of biochar supported nano zero-valent iron (BC/nZVI) with different carbon/iron ratios on two-phase anaerobic digestion (AD) of food waste (FW) were studied. Results suggested that when the carbon/iron ratio was 3:1 AD system showed the best performance, with the concentration of volatile fatty acids (VFAs) in acidogenic phase (AP) and the cumulative methane production in methanogenic phase (MP) increased by 31.4% and 24.8%, respectively. Metagenomic analysis demonstrated that BC/nZVI increased the relative abundance of Defluviitoga in AP, and promoted the growth of Methanothrix in MP. Metabolic pathway analysis in AP indicated that BC/nZVI mainly promoted the abundances of acetate kinase and butyrate kinase to enhance acid production. Methane metabolism pathway analysis in MP revealed that BC/nZVI increased methane production by promoting the module of M00357 and activating related enzymes. The results of this sutdy showed that BC/nZVI promoted AD of FW mainly through acetoclastic methanogenic pathway.


Diagnosis of amyotrophic lateral sclerosis.
This review of the differential diagnosis of amyotrophic lateral sclerosis focuses on two themes. The first is practical, how to establish the diagnosis based primarily on clinical findings buttressed by electrodiagnosis. The main considerations are multifocal motor neuropathy and cervical spondylotic myelopathy. The second theme is the relationship of motor neuron disease to other conditions, including benign fasciculation (Denny-Brown, Foley syndrome), paraneoplastic syndromes, lymphoproliferative disease, radiation damage, monomelic amyotrophy (Hirayama syndrome), as well as an association with parkinsonism, dementia and multisystem disorders of the central nervous system.


Predicting adverse outcomes in pregnant patients positive for SARS-CoV-2: a machine learning approach- a retrospective cohort study.
Pregnant people are particularly vulnerable to SARS-CoV-2 infection and to ensuing severe illness. Predicting adverse maternal and perinatal outcomes could aid clinicians in deciding on hospital admission and early initiation of treatment in affected individuals, streamlining the triaging processes. An international repository of 1501 SARS-CoV-2-positive cases in pregnancy was created, consisting of demographic variables, patient comorbidities, laboratory markers, respiratory parameters, and COVID-19-related symptoms. Data were filtered, preprocessed, and feature selection methods were used to obtain the optimal feature subset for training a variety of machine learning models to predict maternal or fetal/neonatal death or critical illness. The Random Forest model demonstrated the best performance among the trained models, correctly identifying 83.3% of the high-risk patients and 92.5% of the low-risk patients, with an overall accuracy of 89.0%, an AUC of 0.90 (95% Confidence Interval 0.83 to 0.95), and a recall, precision, and F1 score of 0.85, 0.94, and 0.89, respectively. This was achieved using a feature subset of 25 features containing patient characteristics, symptoms, clinical signs, and laboratory markers. These included maternal BMI, gravidity, parity, existence of pre-existing conditions, nicotine exposure, anti-hypertensive medication administration, fetal malformations, antenatal corticosteroid administration, presence of dyspnea, sore throat, fever, fatigue, duration of symptom phase, existence of COVID-19-related pneumonia, need for maternal oxygen administration, disease-related inpatient treatment, and lab markers including sFLT-1/PlGF ratio, platelet count, and LDH. We present the first COVID-19 prognostication pipeline specifically for pregnant patients while utilizing a large SARS-CoV-2 in pregnancy data repository. Our model accurately identifies those at risk of severe illness or clinical deterioration, presenting a promising tool for advancing personalized medicine in pregnant patients with COVID-19.


[Stapes fixation and proximal symphalangism caused by autosomal dominant transmission (author's transl)].
A family showed in four generations the syndrome of stapes fixation and proximal symphalangism with changing expressivity caused by autosomal dominant transmission.


Scintigraphic features of malignant epithelioid hemangioendothelioma.
The scintigraphic features of malignant epithelioid hemangioendothelioma of the liver have not been previously documented. In particular, there are no reports on the nature of gallium uptake in these rare tumors. The case reported is a young woman with primary hepatic epithelioid hemangioendothelioma. Metastatic disease in the skull was detected on a Tc-99m MDP bone scan. A Ga-67 study demonstrated that this tumor was not gallium avid.


Epidemiology and outcomes of gastrointestinal mucosal melanomas: a national database analysis.
Gastrointestinal malignant melanoma is a rare mucosal melanoma (MM). Other MM include the respiratory and the genitourinary tract. All mucosal melanomas have a poor prognosis when compared to cutaneous melanomas. Ano-rectal melanomas are by far the most common and most studied gastrointestinal MM. Large-scale clinical data is lacking due to the rarity of the disease. We aim to analyze epidemiology and survival of the Gastrointestinal (G.I.) MM over 45 years using a national database. The Surveillance, Epidemiology and End Results (SEER) database was queried to identify patients with biopsy-proven G.I. Melanomas. We selected tumor site, intervention, and survival information for oncology codes as per the international classification of diseases. Survival analysis was performed using the SPSS v 27 ® IBM software. Of the 1105 biopsy-proven confirmed cases of primary G.I. melanoma's, 191 (17.3%) received chemotherapy (C.T.), 202 (18.3%) received radiotherapy (R.T.), 63 (5.7%) received both C.T and R.T., while 684 (61.9%) of the population received surgery alone or combined with C.T. and/or R.T. Statistically significant improvement in survival was noted in all treatment strategies that utilized surgery and also when site-specific MM cohorts underwent a surgical approach with or without C.T and/or R.T. This is the most extensive study reporting epidemiological and survival data of treatment strategy outcomes of primary G.I. mucosal melanoma elucidating best overall survival with a management strategy involving surgical intervention.


Gene structure of rat testicular cell adhesion molecule 1 (TCAM-1), and its physical linkage to genes coding for the growth hormone and BAF60b, a component of SWI/SNF complexes.
In the +9.7 to +21.7kb downstream region from the transcriptional start site of the rat growth hormone (GH) gene, a gene specifically expressed in the testis was found to have reverse transcriptional orientation to the GH gene. Its exon comprised 2693 bases encoded a protein having 548 amino acids (60479Da). The amino acid sequence of the testis-specific protein resembled that of the intercellular adhesion molecules (ICAM) 1 and 3. The gene was thus given the name testicular adhesion molecule (TCAM) 1 gene. The TCAM-1 gene was found to be 12041 bases with eight exons. Although exon 1 was noncoding, the remaining seven exons corresponded to the domains coding for the signal sequence, five immunoglobulin (Ig) domains, and the transmembrane plus cytoplasmic domain. The organization of TCAM-1 gene was shown to be the same as that of the ICAM-1 gene. The polyadenylation site of TCAM-1 gene was located 7.6kb downstream of that of the GH gene, whereas the 5' end of TCAM-1 gene was separated 5.9kb from that of the gene coding for BAF60b, a component of SWI/SNF complexes known as the chromatin remodeling factor. Six genes were thus mapped in the following order in the 88kb region of the rat GH locus: Na-channel (5' to 3')-B29/Ig-beta (5' to 3')-GH (5' to 3')-TCAM-1 (3' to 5')-BAF60b (5' to 3')-SUG/p45 (3' to 5').


Calcitonin, zinc, and testicular function.
Recent studies demonstrating decreases in transport kinetics of zinc (Zn) in testis in response to calcitonin (CT) and the presence of CT receptors on Leydig cells has suggested a physiological interrelationship between CT and cellular Zn metabolism in the testis. The present studies were undertaken to evaluate the acute effects of human synthetic calcitonin (hCT) on testosterone (T) synthesis and on transmembrane Zn transport as measured in a closed two-compartment model system in Leydig cells isolated from intact and thyroparathyroldectomized (TPTX) rats. Leydig cells acutely exposed to 1 ng/mL equine luteinizing hormone (LH) in vitro had a fivefold increase in medium T concentration. Calcitonin at 42 micrograms/mL had no effect on the basal T synthesis and did not affect the increase seen after LH administration. Lower doses of LH demonstrated a dose response for T production, but no alteration in the pattern of response. In TPTX rats pretreated with 167 micrograms/d (25 MRC U/d) hCT subcutaneously (sc) for three days before they were killed, a reduction to 73% of the control value was observed in the in vitro Leydig cell fractional influx coefficient for Zn transport (P less than .02). No difference was observed in the fractional efflux coefficient. Fractional flux coefficients from intact rats demonstrated qualitatively similar, but more variable, changes. These data demonstrate that there is no acute effect of CT on T synthesis in the isolated Leydig cell. There does appear, nevertheless, to be a role for CT in the modulation of transmembrane Zn transport. Clinically important Zn-dependent alterations of T synthesis may require long-term changes in Zn metabolism before they become manifest.(ABSTRACT TRUNCATED AT 250 WORDS)


Semi-quantitative measurements of chemokine receptor 4-targeted 68Ga-pentixafor PET/CT in response assessment of Waldenström macroglobulinemia/lymphoplasmacytic lymphoma.
68Ga-pentixafor PET/CT was reported to have a high sensitivity in detecting tumor involvement of Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) in our previous study. We aimed to further investigate the semi-quantitative measurements of 68Ga-pentixafor PET/CT in response assessment in WM/LPL. Fifteen patients with WM/LPL were recruited in a prospective cohort study and underwent both 68Ga-pentixafor and 18F-FDG PET/CT at baseline and post-treatment. PET/CT-based responses were analyzed with semi-quantitative assessments of metabolic tumor volume (MTV) and total lesions glycolysis/uptake (TLGFDG and TLUCXCR4), and the correlation between PET/CT-based response and clinical response, monoclonal protein and IgM response was analyzed. After chemotherapy, 5 patients had complete response or very good partial response, 8 had partial response or minimal response and 2 had progressive disease. In quantitative analysis, 68Ga-pentixafor PET/CT-based response (measured in ∆TLUCXCR4%, ∆MTVCXCR4%, ∆SUVpeak%) showed a significant direct correlation with clinical response, monoclonal protein and IgM response (p < 0.01). However, 18F-FDG PET/CT-based response was independent from clinical response (p > 0.05). The semi-quantitative measurements of 68Ga-pentixafor PET/CT outperformed 18F-FDG PET/CT in response assessment of WM/LPL.


Cross-Sectional Imaging Findings of Atypical Liver Malignancies and Diagnostic Pitfalls: Emphasis on Computed Tomography, and Magnetic Resonance Imaging.
Atypical liver malignancies can either be uncommon presentations of commonly encountered liver malignancies or rare tumors infrequently seen in clinical practice and often pose a challenge in diagnostic imaging interpretation. These lesions tend to be highly variable in their imaging appearance and are less well discussed in the literature. Commonly, an inter-disciplinary approach incorporating clinical information, imaging data, and histopathology is needed to reach an accurate diagnosis. The diagnostic radiologist's knowledge of such liver malignancies can aid the clinical team in reaching the correct diagnosis and enabling appropriate management. In this article, we review certain technical considerations and focus on the unusual appearances of common primary and secondary malignant liver lesions, uncommon malignant liver lesions, with emphasis on computed tomography (CT) and magnetic resonance imaging (MRI).


Simultaneous determination of psychosine and cerebrosides.
A new method was developed for the simultaneous determination of psychosine and cerebrosides in tissues. Total lipids extracted from the tissues were treated with [3H]acetic anhydride in toluene-methanol. Known amounts of nonradioactive N-acetylpsychosine were added to the reaction product and then subjected to mild alkaline methanolysis. After the product was washed, it was fractionated by silica gel column chromatography and the fraction containing glycolipids was benzoylated. The benzoylated product was finally fractionated on TLC. The amounts of benzoylated derivatives of nonhydroxy- and hydroxycerebrosides and N-acetylpsychosine were determined using a scanning densitometer. The amounts of psychosine in tissues were calculated from the radioactivity in the spot of N-acetylpsychosine and the recovery of added carrier N-acetylpsychosine. This method allowed us to determine 5 to 1000 pmol of psychosine and 1 to 20 nmol of cerebrosides in peripheral nerves and other tissues of the twitcher mouse as well as transfected Schwann cells derived from the sciatic nerves.


Ultrasound in the diagnosis and measurement of aneurysms of the abdominal aorta.
One hundred cases clinically diagnosed as aneurysm of the abdominal aorta were examined by ultrasound. The findings are described and the value and limitations of the method assessed.


Ulnocarpal abutment after wrist arthrodesis.
We report three patients aged from 22 to 34 years, in whom ulnocarpal abutment developed after wrist arthrodesis. Two were treated by excision of the triquetrum and one by excision of the pisiform. The three patients were seen after wrist fusion because of ulnar wrist pain on forearm rotation, which was relieved by excision of a carpal bone. Two patients had had wrist arthrodesis because of wrist pain resulting from degenerative arthritis and silicone synovitis resulting from silicone rubber replacement of the lunate as treatment for Kienböck's disease. One patient had had a wrist arthrodesis to treat degenerative arthritis after an intra-articular distal radius fracture. The arthrodeses were all done with an A. O. plate and iliac crest bone graft. One patient gained forearm rotation after the excision of the carpal bone and none of the patients lost rotation. The average follow-up was 16 months.


Dissipation and residue of 2,4-D in citrus under field condition.
The dissipation, residues, and risks of 2,4-dicholrophenoxyacetic acid (2,4-D) in citrus under field condition were investigated based on a simple ultra-performance LC (UPLC)-MS/MS method. The results indicated that the residue level of 2,4-D in citrus did not degrade gradually with sampling time under field condition. At pre-harvest intervals (PHI) of 20-40 days, 2,4-D residues were 0.021-0.269 mg/kg in citrus flesh, 0.028-0.337 mg/kg in whole citrus, and 0.028-0.376 mg/kg in citrus peel, all bellow the China maximum residue limit in citrus (1 mg/kg). Risks of 2,4-D were assessed by calculation of risk quotient, and the results revealed no significant health risks after consumption of citrus.


Agenesis of the corpus callosum, infantile spasms, spastic quadriplegia, microcephaly and severe mental retardation in three siblings.
A sibship consisting of three siblings, one male and two females with unrelated parents, showed a clinical syndrome including: infantile spasms with hypsarrhythmia, microcephaly, severe mental retardation and spastic quadriplegia. The pneumoencephalogram performed in two sibs showed agenesis of the corpus callosum and aqueductal stenosis with tri-ventricular dilatation. The disorder did not show a progressive course with deterioration of mental and neurologic functions. No biochemical or cytogenetic defect could be identified. Complement fixation for cytomegalovirus was negative. This syndrome complex is probably inherited as an autosomal recessive trait. The clinical and the genetic aspects of the syndrome are discussed.


The T4 mot protein functions as part of a pre-replicative DNA-protein complex.
Middle-mode RNA synthesis in T4-infected cells takes place before replication of phage DNA commences. What distinguishes it from early-mode RNA synthesis is that initiation of middle RNA depends on T4-coded proteins, in particular on the mot gene product. mot protein is localized in a DNA-protein complex which forms during the first few minutes of infection. All of the cell's mot protein is bound in this complex, and it continues to be bound long after the synthesis of mot protein has stopped. When we infect Escherichia coli with T4 carrying a temperature-sensitive mutation in the mot gene, we find a correlation between the physiology of this mot mutant and the amount of mot protein bound in the DNA-protein complex. Although there is some host RNA polymerase in the complex, mot protein does not seem to bind to this enzyme. Two other T4-coded proteins, of molecular weights 17,600 and 15,000, are also found in the pre-replicative DNA-protein complex. One of these, p17,600, is coded for by a 750-base pair region located between genes 39 and 56; p17,600 appears to be the recently described motB gene product. The other protein, p15,000, is not an RNA polymerase-binding protein; it is characterized by its strong binding to the DNA-protein complex.


The GTPase activity and isoprenylation of Swine GBP1 are critical for inhibiting the production of Japanese Encephalitis Virus.
Japanese encephalitis virus (JEV) is a flavivirus that cause severe neurological deficits. The guanylate-binding protein 1 (GBP1) gene is an interferon-stimulated gene and exerts antiviral functions on many RNA and DNA viruses via diverse mechanisms, however, the roles and the action modes of GBP1 in the antiviral effect on the production of JEV RNA and infectious virions remain to be clarified. In this study, we found that the RNA levels of swine GBP1 (sGBP1) in PK15 cells were up-regulated at the late stage of JEV infection. The overexpression of sGBP1 significantly inhibited the production of JEV while the knockdown of sGBP1 promoted the production of JEV. The GTPase activity and isoprenylation of sGBP1 both are critical for anti-JEV activity. The GTPase activity of sGBP1 is responsible for inhibiting the production of JEV genomic RNA. The isoprenylation of sGBP1 inhibited the expression and cleavage of JEV prM to decrease the yields of infectious virions, which may be associated with the interaction between sGBP1 and cellular proprotein convertase furin. Taken together, the study dissected the action modes of sGBP1with potent anti-JEV activity in more details.


A preliminary study of KAT2A on cGAS-related immunity in inflammation amplification of systemic lupus erythematosus.
Previous studies demonstrated that cGAS pathway is related to the inflammation amplification in a variety of autoimmune diseases. Lysine acetyltransferase family (KATs) can regulate the nuclear transcription or cytoplasmic activation of cGAS through different mechanisms. However, its role and related immunity patterns in systemic lupus erythematosus (SLE) have not been explored. In this study, RNA-seq and scRNA-seq profiling were performed for peripheral blood mononuclear cells (PBMCs) from patients with SLE. R packages were used for bioinformatic analysis. Cell culture, RT-PCR, western blotting, immunofluorescence, immunohistochemistry, and ELISA were used to explore gene expression in vitro or clinical specimens. Plasmid transfection and mass spectrometry were used to detect protein modifications. Eight acetyltransferase and deacetylase family members with significantly differential expression in SLE were found. Among them, KAT2A was abnormally upregulated and positively correlated with disease activity index. Further, KAT2A-cGAS pathway was aberrantly expressed in specific immune cell subsets in SLE. In vitro studies showed KAT2A modulated cGAS through increasing expression and post-translational modification. Our research provides novel insights for accurately positioning specific immune-cell subgroups in which KAT2A-cGAS reaction mainly works and KAT2A regulation patterns.


A correlation of serum C3DP levels with chemotherapeutic management of cancer patients.
Serial serum C3DP levels of 33 patients at our institution have been followed for up to 10 months. Individuals experiencing periods free of symptoms and signs of proliferating or expanding malignant disease, had C3DP levels which remained below 150 microgram/ml. Patients with active or recurrent disease, while on chemotherapy, had elevated C3DP values (greater than 150 microgram/ml). Serum C3DP values declined abruptly following treatment which resulted in major reduction of tumor mass. Decreases in C3DP levels from values above 150 microgram/ml to values within the normal range (50-150 microgram/ml) were observed during 89% (25/28) of the favorable clinical responses which have been followed with C3DP assays. Increases in C3DP levels from values within the normal range to values above 150 microgram/ml were observed either prior to or coordinate with clinical symptoms of disease recurrence 83% of the time (10/12 cases). These studies suggest that serial C3DP determinations offer an excellent prognostic aid for evaluating the response of malignant tumors during chemotherapeutic management.


The importance of load-independent analysis in assessment of the inotropic effect of prostaglandin E1 in vivo.
Load-independent pressure-dimension analysis was applied in 13 open-chest, anesthetized dogs during either left atrial (n = 7) or right atrial (n = 6) infusion of prostaglandin E1. Right atrial infusion of prostaglandin E1 in doses from 31 to 500 ng/kg/min resulted in no change in any parameters studied, including mean arterial pressure, cardiac output, and systemic and pulmonary vascular resistances. Left atrial infusion of prostaglandin E1 produced dose-dependent reductions in mean arterial pressure and systemic vascular resistance but no change in the slope of the relationship of left ventricular stroke work to end-diastolic length, a load-independent index of ventricular performance. In contrast to findings obtained with load-dependent parameters, these results suggest that prostaglandin E1 has no positive inotropic effect in vivo.


Fluocinolone acetonide intravitreal implant (Iluvien®): in diabetic macular oedema.
Fluocinolone acetonide intravitreal implant (Iluvien®) is an injectable, non-erodible, corticosteroid implant that is approved in several European countries for the treatment of chronic diabetic macular oedema (DMO). In analyses of two multinational trials in patients with DMO previously treated with macular laser photocoagulation, fluocinolone acetonide intravitreal implant 0.2 μg/day was significantly more efficacious than sham injection in improving visual acuity. At 24 months post injection, 29 % of fluocinolone acetonide intravitreal implant 0.2 μg/day recipients had an improvement in the best-corrected visual acuity (BCVA) letter score of ≥15 compared with 16 % in the sham injection group (p = 0.002) [primary endpoint]. Treatment benefit was most evident in the subgroup of patients whose duration of DMO was ≥3 years. In this subgroup at 36 months, 34 % of fluocinolone acetonide intravitreal implant 0.2 μg/day recipients had an increase in the BCVA score of ≥15, compared with 13 % of sham injection recipients (p < 0.001). Fluocinolone acetonide intravitreal implant recipients also had generally greater benefits than sham injection recipients on secondary endpoints. In patients who were phakic in the study eye at baseline, cataracts occurred in 82 % of fluocinolone acetonide intravitreal implant 0.2 μg/day recipients and 51 % of sham injection recipients. Overall, 37 % and 12 % of patients in the fluocinolone acetonide intravitreal implant and sham injection groups developed raised intraocular pressure (IOP), which was generally controlled with IOP-lowering drugs.


Contraceptive efficacy, compliance and beyond: factors related to satisfaction with once-weekly transdermal compared with oral contraception.
To investigate contraceptive efficacy, compliance and user's satisfaction with transdermal versus oral contraception (OC). Randomized, open-label, parallel-group trial conducted at 65 centers in Europe and South Africa. One thousand four hundred and eighty-nine women received a contraceptive patch (n = 846) or an OC (n = 643) for 6 or 13 cycles. Overall/method-failure Pearl Indices were 0.88/0.66 with the patch and 0.56/0.28 with the OC (p = n.s.). Compliance was higher at all age groups with the patch compared to the OC. Significantly more users were very satisfied with the contraceptive patch than with the OC. The percentage of patch users being very satisfied increased with age whereas it did not in the OC group. Likewise, improvements of premenstrual symptoms as well as emotional and physical well-being increased with age in the patch-group in contrast to the OC group. Ratings of satisfaction with the study medication correlated weakly with emotional (r = 0.33) and physical well-being (r = 0.39) as well as premenstrual symptoms (r = 0.30; p < 0.001). Contraceptive efficacy of the patch is comparable to OC, but compliance is consistently better at all age groups. Higher satisfaction with the patch at increasing age may be attributed to improvements in emotional and physical well-being as well as reduction of premenstrual symptoms.


Export of proteins from oocytes of Xenopus laevis.
When human lymphoblastoid mRNA was microinjected into X. laevis oocytes, titers of interferon rapidly reached a maximum inside the oocyte while accumulation of interferon continued in the incubation medium for at least 45 hr. If interferon protein was injected into oocytes it was rapidly inactivated. Significantly, newly synthesized interferon but not injected interferon was found to be membrane-associated. Further experiments involving the co-injection of mRNAs coding for secretory proteins (guinea pig milk proteins and human interferon) and nonsecretory proteins (rabbit globin) revealed that only the secretory proteins were exported from the oocyte. Moreover, different proteins were exported at different rates. A distinct subclass of newly synthesized oocyte proteins of unknown function also accumulated in the incubation medium. Since the information encoded in the messenger RNAs of secretory proteins is sufficient to specify synthesis, compartmentation and secretion of these proteins, the oocyte may provide a complete system for the analysis of the secretory process.


Cognitive behavioral therapy for overactive bladder in women: study protocol for a randomized controlled trial.
Overactive bladder (OAB) symptoms affect daily life by decreasing health-related quality of life (HRQol). However, there remain no very effective treatment for OAB. Pharmacotherapy is one of the best treatments, but it is not always efficient and may incur adverse events. Although behavioral therapy is another effective treatment, there are very few structured treatment manuals on how to prescribe behavioral therapy to treat OAB for whom. Cognitive behavioral therapy (CBT) is a psychotherapy consisting of structured sessions to solve problems with the collaborative empiricism between therapists and patients. OAB symptoms are supposed to worsen with cognitive distortion, and CBT is expected to be effective in treating OAB by modifying such cognitive processes. In this trial, we will evaluate the efficacy of CBT for OAB. A randomized, controlled, open-label, multicenter parallel-group superiority trial will be conducted. Participants with moderate to severe OAB symptoms with or without pharmacotherapy will be recruited and will be randomly allocated 1:1 to two different groups by minimization (age, baseline OAB severity, treatment status, types of intervention, and treating institutions). The intervention group will be prescribed an individual CBT program covering six techniques in 4 sessions (30 min each), with or without pharmacotherapy. The primary outcome is the change scores in an OAB-questionnaire (OAB-q) from baseline to the end of the trial (week 13). Secondary outcomes will include other patient reported outcome measures and the frequency volume chart. All analyses will be conducted on an intention-to-treat principle. This trial will determine the efficacy of CBT to treat OAB using a rigorous methodology. The effectiveness of CBT with a structured manual may not only lead to a new treatment option for patients suffering from OAB symptoms, but may also reduce the social burden by OAB. UMIN-CTR Clinical Trial, CTR-UMIN000038513 . Registered on November 7, 2019.


Immunopathological immunohistochemical study of low pathogenic avian influenza virus H5N1 infection in lovebirds (Agapornis spp.) in Indonesia.
To date, persistent infection with low pathogenic avian influenza virus (AIV) subtype H5N1 (LPAI H5N1) in chickens is widespread in Indonesia. Commercially available ornamental birds on markets play an important role in triggering the occurrence of AIV outbreaks. Thus, the presence of AIV in ornamental birds such as lovebirds needs to be closely monitored. Here, the presence of LPAI H5N1 was investigated in lovebirds with no clinical signs that, although apparently healthy, can be a continuous source of AIV transmission to other sensitive birds such as chickens and even humans. In the present study, 30 lovebirds were necropsied. The immunopathology of the lungs, which had hemorrhages, was immunohistochemically studied using the streptavidin-biotin (SB) method to stain for LPAI H5N1. Polyclonal antibodies against the nucleoprotein or monoclonal antibodies against the hemagglutinin of the AIV subtype H5N1 were used to identify these antigens in lung tissue samples. LPAI H5N1 was detected in the lungs of all lovebirds according to the brownish colored deposits in the histological samples. The highest intensity of the SB staining was found in the lumina of vascular capillaries and the cell membranes of air capillaries. The discovery of LPAI H5N1 in lovebirds increases the environmental health risk and raises the possibility of exposure to AIV. Thus, it is very important to improve the mechanisms that control the traffic of ornamental birds between regions and islands, as well as the AIV vaccination strategies related to the prevention, control, and eradication of AIV in Indonesia, and these procedures should be reevaluated. The present study proves that lovebirds are infected with LPAI subtype H5N1. Even if ornamental birds such as lovebirds do not show any clinical signs, they are likely to be a persistently infected with LPAI H5N1. Therefore, ornamental birds might be a continuous source of LPAI H5N1 infections in other sensitive birds, including poultry, and may also be responsible for virus transmission to humans.


New materials and devices for preventing catheter-related infections.
Catheters are the leading source of bloodstream infections for patients in the intensive care unit (ICU). Comprehensive unit-based programs have proven to be effective in decreasing catheter-related bloodstream infections (CR-BSIs). ICU rates of CR-BSI higher than 2 per 1,000 catheter-days are no longer acceptable. The locally adapted list of preventive measures should include skin antisepsis with an alcoholic preparation, maximal barrier precautions, a strict catheter maintenance policy, and removal of unnecessary catheters. The development of new technologies capable of further decreasing the now low CR-BSI rate is a major challenge. Recently, new materials that decrease the risk of skin-to-vein bacterial migration, such as new antiseptic dressings, were extensively tested. Antimicrobial-coated catheters can prevent CR-BSI but have a theoretical risk of selecting resistant bacteria. An antimicrobial or antiseptic lock may prevent bacterial migration from the hub to the bloodstream. This review discusses the available knowledge about these new technologies.


Metastatic solid tumors to the testis: a clinicopathologic evaluation of 157 cases from an international collaboration.
To elucidate the spectrum of metastatic solid tumors to the testis and their clinicopathologic features. The databases and files of 26 pathology departments from 9 countries on 3 continents were surveyed to identify metastatic solid tumors to the testis and to characterize their clinicopathologic features in detail. We compiled a series of 157 cases of metastatic solid tumors that secondarily involved the testis. The mean patient age at diagnosis was 64 years (range, 12-93 years). Most patients (127/144; 88%) had clinical manifestation of the disease, with testicular mass/nodule (89/127; 70%) being the most common finding. The main mechanism of testicular involvement was metastasis in 154/157 (98%) cases. Bilateral testicular involvement was present in 12/157 (8%) patients. Concurrent or prior extratesticular metastases were present in 78/101 (77%) patients. The diagnosis was made mainly in orchiectomy specimens (150/157; 95%). Different types of carcinomas (138/157; 87%), most commonly adenocarcinoma (72/157; 46%), were the most common malignancies. The most common primary carcinomas included prostatic (51/149; 34%), renal (29/149; 20%), and colorectal (13/149; 9%). Intratubular growth was identified in 13/124 (11%) cases and paratesticular involvement was found in 73/152 (48%) cases. In patients with available follow-up (110/157; 70%), more than half (58/110; 53%) died of disease. In this largest series compiled to date, we found that most secondary tumors of the testis represent metastases from the genitourinary and gastrointestinal tract carcinomas and typically occur in the setting of disseminated disease.


Corrigendum: Correlation Between Lung Density Changes Under Different Dose Gradients and Radiation Pneumonitis-Based on an Analysis of Computed Tomography Scans During Esophageal Cancer Radiotherapy.
[This corrects the article DOI: 10.3389/fonc.2021.650764.].


Oral plasmablastic lymphoma in an HIV-negative patient: a case report and review of the literature.
Plasmablastic lymphoma is an HIV-associated non-Hodgkin's lymphoma that primarily affects the oral cavity and jaws. The purpose of this report is to describe the first case of plasmablastic lymphoma occurring in an HIV-negative, nonimmunocompromised individual, and to review the histopathologic and immunohistochemical phenotype of this lymphoma. Histopathologically, our case exhibited a dense, diffuse lymphocytic infiltrate of noncohesive large lymphocytes with plasmacytoid features. Immunohistochemical analysis revealed positivity for the B-cell marker CD79a, VS38c, Epstein-Barr virus latent membrane protein (LMP), immunoglobulin G (IgG), and lambda light chain restriction. Neoplastic cells were negative for leukocyte common antigen, CD20, CD3, CD10, CD138, Bcl-2, Bcl-6, desmin, actin, EMA, S-100, HMB45, Alk-1, HHV8, IgA, IgM, and cytokeratin. The features of this rare disease are summarized based on a comprehensive review of the epidemiologic, clinical and immunohistochemical findings of previously reported cases.


Effect of silane reagent functionality for fluorinated alkyl and phenyl silica bonded stationary phases prepared in supercritical carbon dioxide.
This research examines the effect of silane reagent functionality for the preparation of fluorinated alkyl silica-bonded stationary phases prepared using supercritical carbon dioxide (sc-CO(2)) as a bonding medium. We present results that demonstrate that alkyl (C(8) and C(10)) and phenyl (pentafluorophenylpropyl, PFPP) silica bonded stationary phases can be prepared under sc-CO(2) conditions of 100 degrees C, 414bar and 3h, with surface coverages comparable to those obtained using organic solvent based methods. Fluorinated alkyl silica bonded phase preparation with a trichloro silane generates high ligand densities and more chemically uniform silica surface species compared to phases prepared using a monochloro or alkoxy silanes, as evidenced by thermogravimetric analysis (TGA) and (29)Si cross polarisation magic angle spinning (CP-MAS) NMR spectroscopy. In addition, the sc-trichloro prepared fluorinated C(8) bonded phases have demonstrated the ability to separate solutes on the basis of their molecular shape with the separation of the LC column shape selectivity test mixture, SRM 869a in the elution order of PhPh<BaP=TBN with a selectivity value of alpha(TBN/BaP)=1.0. These chromatographic findings are indicative of a fluorinated C(8) silica bonded stationary phase that is capable of some shape recognition.


Sex determination from pulp tissues of teeth subjected to different physical conditions and times after extraction.
The purpose of this study was to determine the reliability of sex determination from observation of Barr bodies in cells of tooth pulp tissue subjected to different physical conditions and duration of time after extraction. The study comprised 150 teeth of subjects (male 50% and female 50%) who were randomly sampled. The teeth were grouped according to the conditions and times they were subjected to before extirpation of pulp tissues as follows: immediately after extraction; after 1 month in stagnant water; after staying at room temperature for 1 month, 3 months and 5 months post extraction and; after being subjected to varied degrees of temperature. The pulp tissues were fixed in 10% formal saline and processed for H&E stain. The presence of a cell with visible Barr body was considered positive for women. Sex chromatin were observable in the female preparations up to a duration of five months after extraction; teeth left in stagnant water for 1 month; and teeth subjected to temperature up to 400 degrees C. There was no positive cell in preparations of male subjects. Teeth pulp tissues are reliable evidence in forensic human identification by sex in varied physical conditions and times of death.


Pharmacokinetics and pharmacodynamics of a short- and long-acting theophylline medication (Theolair and Theolair retard) in normals and asthmatics. Part II: Lung function and side effects.
Six normals and six patients with chronic obstructive lung disease were treated with a short- and long-acting theophylline (Theolair and Theolair retard). During treatment the lung function data of the patients showed an improvement on day 1, but no further improvement on days 4 and 7, despite the higher theophylline plasma concentration on these last days. There was no close correlation between the improvement of lung function and the theophylline plasma concentration, nor was there any difference between Theolair and Theolair retard as regards improvement of lung function. Side effects were negligible, and the theophylline plasma concentration was rather low. It seems advisable to use a higher dosage of the theophyllines and perhaps it is even better to combine them with other bronchodilators.


Identification of a novel de novo mutation of SETBP1 and new findings of SETBP1 in tumorgenesis.
In the past decade, SETBP1 has attracted a lot of interest on that the same gene with different type or level (germline or somatic) of variants could provoke different pathologic consequences such as Schinzel-Giedon syndrome, SETBP1 Haploinsufficiency Disorder (SETBP1-HD) and myeloid malignancies. Whole exome sequencing was conducted to detect the etiology of a pregnant woman with mental retardation. As a new oncogene and potential marker of myeloid malignancies, somatic SETBP1 variants in other cancers were rarely studied. We performed a pan-cancer analysis of SETBP1 gene in different cancers for the first time. A novel heterozygous mutation of the SETBP1 gene (c.1724_1727del, p.D575Vfs*4) was found in the patient and the fetus and the mutation was predicted to result in a truncated protein. Reduced SETBP1 expression was associated with SETBP1-HD. The pan-cancer analysis of SETBP1 showed that SETBP1 overexpression should be given special attention in Bladder Urothelial Carcinoma (BLCA) and Stomach adenocarcinoma (STAD). The de novo SETBP1 mutation was the genetic cause of SETBP1-HD in the family. BLCA and STAD might be related to SETBP1 overexpression.


Genetically targeted radiotherapy of head and neck squamous cell carcinoma using the sodium-iodide symporter (NIS).
Gene therapy that uses delivery of the sodium-iodide symporter (NIS) gene followed by radioiodide administration has been proposed as a novel form of radiotherapy for nonthyroidal cancers. In vitro [(125)I] iodide accumulation and efflux from cells was determined after treatment with an NIS-expressing adenovirus (Ad-NIS). A clonogenic survival assay and tumor growth experiment that used athymic mice were used to demonstrate the in vitro and in vivo cytotoxicity of Ad-NIS treatment and [(131)I] iodide delivery. Head and neck squamous cell carcinoma (HNSCC) cell lines treated with Ad-NIS exhibit significant amounts of radioiodide accumulation and retention. In vitro HNSCC cell survival was significantly diminished after NIS gene delivery followed by administration of [(131)I] iodide. Moreover, NIS gene transfer/[(131)I] iodide administration dramatically attenuated HNSCC tumor formation in athymic mice. Our data demonstrate the feasibility of genetically targeted radiotherapy by use of the NIS gene as a possible therapeutic intervention in head and neck cancer.


Short report: hematologic changes in acute, imported Plasmodium falciparum malaria.
We conducted a retrospective analysis of hematologic changes in 89 patients with imported Plasmodium falciparum malaria. Thirteen (15%) were anemic at presentation, 60 (67%) had thrombocytopenia, and 63% had lymphopenia. There was a significant inverse relationship between parasitemia and platelet count. Anemia is rare among patients with imported malaria, while thrombocytopenia and lymphopenia are common.


Splenic Vein Embolization Using Coil Anchors and Prophylactic Occlusion of a Hepatofugal Collateral for Hepatic Encephalopathy due to Splenorenal Shunt: Technical Note and Literature Review.
Purpose. Interventional treatment strategies for patients with encephalopathy due to splenorenal shunt remain controversial. Portosplenic blood flow separation by occluding the splenic vein could avoid the complication of severe portal hypertension, but it would require repeated reintervention due to recurrence of symptoms. This paper describes occlusion of the splenic vein using coil anchors and prophylactic embolization of a collateral hepatofugal vessel with no recurrence of hyperammonemia. Materials and Methods. A 51-year-old woman with severe cirrhosis had hepatic encephalopathy due to a large splenorenal shunt. The serum ammonia level was 132 μ g/dL. Via a transileocolic approach, the splenic vein was completely embolized with 0.035-inch metallic coils using coil anchors while preserving the splenorenal shunt. In addition, one of the collateral vessels of the portal vein, the retrogastric vein, was also embolized prophylactically. Results. After this procedure, the serum ammonia level decreased immediately to 24 μ g/dL. The portal venous pressure increased by only 1.5 mmHg. Hepatic encephalopathy had not been observed for 25 months after the procedure, and neither retention of ascites nor worsening of esophageal varices and liver function was observed. Conclusion. This procedure appears to be safe and effective for hepatic encephalopathy caused by a splenorenal shunt.


B-type natriuretic peptide in cardiovascular disease.
Natriuretic peptide hormones, a family of vasoactive peptides with many favourable physiological properties, have emerged as important candidates for development of diagnostic tools and therapeutic agents in cardiovascular disease. The rapid incorporation into clinical practice of bioassays to measure natriuretic peptide concentrations, and drugs that augment the biological actions of this system, show the potential for translational research to improve patient care. Here, we focus on the physiology of the natriuretic peptide system, measurement of circulating concentrations of B-type natriuretic peptide (BNP) and the N-terminal fragment of its prohormone (N-terminal BNP) to diagnose heart failure and left ventricular dysfunction, measurement of BNP and N-terminal BNP to assess prognosis in patients with cardiac abnormalities, and use of recombinant human BNP (nesiritide) and vasopeptidase inhibitors to treat heart failure.


Use of primary radiotherapy for rectal cancer in the Netherlands between 1997 and 2008: a population-based study.
To describe variation in the utilisation rates of primary radiotherapy for patients with rectal cancer in the Netherlands, focusing on time trends and age effects. Data on primary non-metastatic rectal cancer were derived from the population-based cancer registries of four comprehensive cancer centres (regions) in the Netherlands (1997-2008, n=13,055). An increase in the utilisation rate was noted for the four regions, from 37-46% in 1997 to 66-76% in 2008, for both genders. This increase was found predominately for preoperative radiotherapy (from 13-31% to 58-67%) and (unsurprisingly) was most pronounced for stage T2-3 patients (from 9-27% to 68-80%). The probability of receiving radiotherapy decreased with age: the odds of receiving preoperative radiotherapy was reduced in patients aged 65 years and older, as well as the odds of receiving postoperative radiotherapy in those aged 75 years and older, which remained significant after adjustment for stage, gender and region. Regional differences persisted in multivariable analyses, i.e. the odds of receiving preoperative radiotherapy was reduced in two regions: odds ratio: 0.4 (95% confidence interval: 0.4-0.5) and 0.7 (0.6-0.8). The odds of receiving postoperative radiotherapy was significantly increased in these regions [odds ratio: 2.6 (2.2-3.2) and 1.6 (1.3-1.9), respectively] and reduced in another [odds ratio 0.8 (0.6-0.96)]. The utilisation rate of radiotherapy for rectal cancer increased significantly over time, particularly for preoperative radiotherapy and was most pronounced for T2-3 patients. Due to national multidisciplinary treatment guidelines, regional differences became limited in recent years after adjustment for age and stage of the disease. A low utilisation rate of radiotherapy was seen in women and elderly patients.


The 2-methoxy group of ubiquinone is essential for function of the acceptor quinones in reaction centers from Rba. sphaeroides.
The orientation of a methoxy substituent is known to substantially influence the electron affinity and vibrational spectroscopy of benzoquinones, and has been suggested to be important in determining the function of ubiquinone as a redox cofactor in bioenergetics. Ubiquinone functions as both the primary (Q(A)) and secondary (Q(B)) quinone in the reaction centers of many purple photosynthetic bacteria, and is almost unique in its ability to establish the necessary redox free energy gap for 1-electron transfer between them. The role of the methoxy substitution in this requirement was examined using monomethoxy analogues of ubiquinone-4 - 2-methoxy-3,5-dimethyl-6-isoprenyl-1,4-benzoquinone (2-MeO-Q) and 3-methoxy-2,5-dimethyl-6-isoprenyl-1,4-benzoquinone (3-MeO-Q). Only 2-MeO-Q was able to simultaneously act as Q(A) and Q(B) and the necessary redox potential tuning was shown to occur in the Q(B) site. In the absence of active Q(B), the IR spectrum of the monomethoxy quinones was examined in vitro and in the Q(A) site, and a novel distinction between the two methoxy groups was tentatively identified, consistent with the unique role of the 2-methoxy group in distinguishing Q(A) and Q(B) functionality.


Impairment of respiratory muscle strength in Berardinelli-Seip congenital lipodystrophy subjects.
Berardinelli-Seip Congenital Generalized Lipodystrophy (BSCL) is an ultra-rare metabolic disease characterized by hypertriglyceridemia, hyperinsulinemia, hyperglycemia, hypoleptinemia, and diabetes mellitus. Although cardiovascular disturbances have been observed in BSCL patients, there are no studies regarding the Respiratory Muscle Strength (RMS) in this type of lipodystrophy. This study aimed to evaluate RMS in BSCL subjects compared with healthy subjects. Eleven individuals with BSCL and 11 healthy subjects matched for age and gender were included in this study. The Maximum Inspiratory Pressure (MIP), Maximum Expiratory Pressure (MEP), and Peripheral Muscle Strength (PMS) were measured for three consecutive years. BSCL subjects were compared to healthy individuals for MIP, MEP, and PMS. Correlations between PMS and MIP were also analyzed. The genetic diagnosis was performed, and sociodemographic and anthropometric data were also collected. BSCL subjects showed significantly lower values for MIP and MEP (p < 0.0001 and p = 0.0002, respectively) in comparison to healthy subjects, but no changes in handgrip strength (p = 0.15). Additionally, we did not observe changes in MIP, MEP, and PMS two years after the first analysis, showing maintenance of respiratory dysfunction in BSCL subjects (p = 0.05; p = 0.45; p = 0.99). PMS and MIP were not correlated in these subjects (r = 0.56; p = 0.18). BSCL subjects showed lower respiratory muscle strength when compared with healthy subjects; however, PMS was not altered. These findings were maintained at similar levels during the two years of evaluation. Our data reveal the first association of BSCL with the development of respiratory muscle weakness.


An emergency medicine clinical problem-solving system.
The availability of complete, accurate, and current medical information is an important aspect of clinical problem solving. As the body of medical information grows and increasingly is reformatted into problem-oriented references, information processing by physicians will grow in importance. The most popular clinical problem-solving method, the Weed problem-oriented medical record, primarily records information; it does not provide an explicit information-processing model. An emergency medicine clinical problem-solving system containing information recording and processing methodologies is presented. The information processing methodology of this system is highlighted.


Dexmedetomidine enables copper homeostasis in cerebral ischemia/reperfusion via ferredoxin 1.
Excessive oxygen free radicals and toxic substances are generated in cerebral ischemia-reperfusion (I/R) process. Dexmedetomidine (DEX), a common anesthetic and sedative drug, can considerably boost glutathione (GSH), which has anti-copper influx effects. Focusing on cuproptosis, the mechanism of DEX in the I/R was revealed. Using the I/R rat model, the effects of DEX and the copper chelator D-penicillamine on cerebral infarct volume, copper levels, mitochondrial respiration and membrane potential, GSH content, and enrichment of cuproptosis functional proteins were examined. The involvement of ferredoxin 1 (FDX1) in the DEX regulatory pathway was verified by overexpressing FDX1 in vitro. DEX could significantly reduce cerebral infarction in rats, reduce copper levels, maintain mitochondrial functions, increase GSH, and reduce the content of key proteins related to cuproptosis. These aspects were replicated in vitro and revealed that FDX1 overexpression partially reversed the impacts of DEX. Together, cuproptosis occurs in the brain I/R process and DEX can enhance cell survival by blocking the primary pathway mediated by FDX1.KEY MESSAGESDexmedetomidine reduces cerebral infarction in the I/R rat models.Dexmedetomidine reduces cuproptosis in the I/R rat models.FDX1, an upstream of protein fatty acylation, mediates regulation of Dexmedetomidine.


Freeze-fracture studies of cytoplasmic inclusions occurring in experimental lipidosis as induced by amphiphilic cationic drugs.
The ultrastructure of cytoplasmic inclusions, which characterize experimental lipidosis as induced by several amphiphilic cationic drugs, was studied by means of freeze-fracturing and thin-sectioning. Retinal and adrenal tissues of rats chronically treated with high oral doses of chlorphentermine were used. In thin sections the cytoplasmic inclusions, which were previously shown to represent lysosomes overloaded with polar lipids, exhibit lamellated or lattice-like internal patterns. The present freeze-fracture observations are interpreted as to indicate that the lamellated inclusions contain polar lipids in the lamellar phase, whereas those with lattice-like patterns contain polar lipids in a hexagonal phase.


A phase 1/2, open-label, parallel group study to evaluate the preliminary efficacy and usability DARE-HRT1 (80 μg estradiol/4 mg progesterone and 160 μg estradiol/8 mg progesterone intravaginal RinGSM) over 12 weeks in healthy postmenopausal women.
The exploratory objectives of this study were to evaluate the usability and acceptability and to conduct a preliminary evaluation of the efficacy of DARE-HRT1. DARE-HRT1 is an intravaginal ring (IVR) that releases 17β2-estradiol (E2) with progesterone (P4) over 28 days. It is the first combination E2 and P4 IVR being developed for the treatment of vasomotor symptoms (VMS) in healthy postmenopausal women with an intact uterus. This was a randomized, open-label, 2-arm, parallel group study in 21 healthy postmenopausal women. Women were randomized (1:1) to either DARE-HRT1 IVR1 (E2 80 μg/d with P4 4 mg/d) or DARE-HRT1 IVR2 (E2 160 μg/d with P4 8 mg/d). They used the assigned IVR for three 28-day cycles, inserting a new IVR monthly. Preliminary genitourinary syndrome of menopause (GSM) treatment efficacy was estimated by measuring changes from baseline in vaginal pH, vaginal maturation index (VMI), and changes in the severity of GSM symptoms. Preliminary systemic VMS efficacy was measured by changes in responses to the Menopause-Specific Quality of Life (MENQOL) questionnaire. Acceptability was assessed by product experience surveys. Preliminary local GSM treatment efficacy was supported by significant decreases in vaginal pH and % parabasal cells, and significant increases in the overall VMI and % superficial cells for both IVR groups (all P values <0.01). Preliminary VMS efficacy was supported by significant decreases in all domains of the MENQOL questionnaire from baseline for both dosing groups (all P values <0.01). Data from this study support further development of DARE-HRT1 for the treatment of menopausal symptoms.


Nectarivory by the plant-tissue feeding predator Macrolophus pygmaeus Rambur (Heteroptera: Miridae): nutritional redundancy or nutritional benefit?
Most predators and parasitoids feed on plant-provided food (nectar, pollen) or engage in herbivory during at least part of their life stages. Plant feeding by these insects plays an important role in driving predator-herbivore dynamics. Thus, understanding the effects of plant feeding on omnivores could be an important element in improving biological control strategies. The mirid Macrolophus pygmaeus is an omnivorous heteropteran predator of whitefly and other pests. Unlike other predators that need to seek out accessible nectar to meet their carbohydrate requirements, mirid bugs can access the plant's carbohydrate resources by feeding directly on plant tissues. Leaf and stem feeding could be seen as a nutritional surrogate that allows mirids to become independent of nectar availability. However, to date feeding experiments have not yet considered nectar feeding by these mirid predators. In this study we demonstrate that M. pygmaeus survival is prolonged on broad bean plants featuring extrafloral nectar as compared to broad bean with extrafloral nectaries removed, irrespective of the presence of cattail pollen. Survival on extrafloral nectar was comparable to the survival by individuals kept on broad bean provided with eggs of Ephestia kuehniella as prey. Also, a greater proportion of mirid females laid eggs when extrafloral nectar was available as compared to those confined on nectariless plants without supplemental food.


The effect of categorization on verbal memory after temporal lobectomy.
Epileptic patients with left or right temporal lobectomies were compared with normal subjects on a verbal memory task involving recall and recognition of categorized and uncategorized word lists. The left temporal group recalled significantly fewer words than the normal control subjects, and recognition performance was also poorer. The right temporal group did not differ significantly from the normal controls on recognition, although differences neared significance on recall. Categorization improved performance in all the groups. The left temporal patients improved if words were presented in order of category membership, but recalled less if category membership was randomized over order of presentation.


Rupture of hidden abnormal myometrial vessels during cesarean delivery of a patient with subserosal leiomyoma: A possible pathogenesis of sudden-onset disseminated intravascular coagulation.
We report a case of sudden-onset disseminated intravascular coagulation during cesarean delivery for a patient with a subserosal leiomyoma. Rupture of hidden anastomotic vessels resulted in a significant decrease in fibrinogen levels and uncontrolled bleeding. Uterine venous flow disturbance caused by subserosal leiomyoma compression can possibly cause such a situation.


Isolated low levels of high-density lipoprotein cholesterol and stroke incidence: JMS Cohort Study.
The cardiovascular relevance of isolated low levels of high-density lipoprotein cholesterol (HDL-C) is yet to be determined. Stroke often leads to long-term disability, and thus, not only stroke mortality but also stroke incidence is a topic of research. Although isolated low HDL-C level has been found to be a predictor for stroke mortality previously, whether it can predict stroke incidence is unknown. In the Jichi Medical School cohort study, 11 025 community-living residents without a history of stroke were examined. Hazard ratios (HRs) for isolated and non-isolated low HDL-C levels were calculated relative to those for normal HDL-C levels in stroke patients using Cox's regression models. During the mean follow-up period of 10.7 years, 412 residents had their first-ever stroke. The multivariable-adjusted HRs for the levels of isolated and non-isolated low HDL-C were 1.11 (95% confidence interval, 0.85-1.44) and 1.35 (1.01-1.81), respectively, when compared to that for normal HDL-C. Low HDL-C levels with other dyslipidemias may contribute to the incidence of stroke, not isolated low HDL-C.


Tris(4-bromophenyl)aminium Hexachloroantimonate as a "Waste-Utilized"-Type Initiator-Promoted C-H Chlorination via C-H Activation Relay: Synthesis of Chlorinated Pyrroles.
Using tris(4-bromophenyl)aminium hexachloroantimonate as a "waste-utilized"-type initiator, the aerobic oxidation of the sp3 C-H bond of proline esters was realized via C-H activation relay, giving a series of halogenated pyrroles in high yields. The mechanistic study revealed that the counterion, SbCl6-, was involved in the radical chlorination process, which provides a new way to understand the role of the counterions.


Profiles of experienced and internalized weight-based stigma in college students across the weight spectrum: Associations with eating disorder, depression, and anxiety symptoms.
Weight stigma comprises negative attitudes and weight-related stereotypes that result in rejection, discrimination, and prejudice against individuals in larger bodies. Both internalized and experienced weight stigma are associated with negative mental health outcomes, yet it remains unknown how types of stigmatizing experiences (e.g., systemic vs. intraindividual), internalized stigma, and weight status relate, or how profiles of weight stigma differentially impact mental health. The current study (N = 1001 undergraduates) used latent profile analysis to identify weight stigma risk profiles and test whether profiles were cross-sectionally associated with eating disorder symptoms, depression, and social appearance anxiety. The best-fitting solution indicated a class high on all facets of weight stigma, a class low on all facets of weight stigma, and three groups with intermediate levels of weight, weight bias internalization, and experienced weight stigma. Gender, but not ethnicity, was associated with class membership. Classes with higher experienced and internalized stigma had higher eating disorder symptoms, depression, and social appearance anxiety. Findings support the utility of weight stigma profiles in identifying risk for negative mental health outcomes. These findings can inform initiatives to reduce weight stigma among college students, especially among high-risk groups.


Phenothiazine--another possible etiologic agent in erythema multiforme. Report of a case.
A case report is presented which offers evidence that administration of a phenothiazine drug resulted in erythema multiforme of the oral cavity in a psychotic patient. The condition remissed after discontinuation of the medication.


Association between G2385R and R1628P polymorphism of LRRK2 gene and sporadic Parkinson's disease in a Han-Chinese population in south-eastern China.
The G2385R and R1628P polymorphisms of the leucine-rich repeat kinase 2 (LRRK2) gene have been reported to be associated with Parkinson's disease (PD), but no data are available on Han-Chinese population of south-eastern China. This study aimed to investigate whether G2385R and R1628P variants are associated with sporadic PD in this population. Total 1,060 subjects were enrolled; including 550 unrelated healthy controls and 510 patients with sporadic PD. Genotyping of polymorphisms was performed by PCR-restriction fragment length polymorphism analysis. All variant samples were sequenced for further confirmation. The results showed that the A allele of the G2385R variant was significantly enriched in sporadic PD patient group (4.8%) when compared with control group [1.1%; odds ratio (OR) 4.58, 95% confidence interval (CI) 2.42-8.65, P < 0.01]. However, no significant difference in the frequency of the C allele of R1628P polymorphism variant was observed between cases and controls (2.8 vs. 1.7%, OR 1.67, 95% CI 0.93-2.99, P = 0.08). In conclusion, this study provides the first evidence that G2385R polymorphism is a risk factor for sporadic PD in Han-Chinese population of south-eastern China.


Effects of solubilization and vanadate/glutathione complex on inhibitor potencies against eosinophil cyclic AMP-specific phosphodiesterase.
Treatment of membranes from guinea-pig peritoneal eosinophils with deoxycholate and NaCl solubilized greater than 95% of the particulate cyclic AMP-specific phosphodiesterase (PDE IV). Solubilized PDE IV was at least 10 times more potently inhibited by selective PDE IV inhibitors (e.g. rolipram, denbufylline) than bound enzyme. Vanadate/glutathione complex (V/GSH) activated membrane-bound PDE IV and also increased potencies of these same inhibitors by at least 10-fold. Neither solubilization nor V/GSH markedly influenced the inhibitory activities of non-selective inhibitors (e.g. trequinsin, dipyridamole). Inhibitor effects on solubilized PDE IV and cyclic AMP accumulation in intact cells were strongly correlated. These results suggest a biologically important site on eosinophil PDE IV which is concealed or partially concealed in freshly prepared membranes and is exposed by solubilization or V/GSH.


The Effects of Castration, Implant Protocol, and Supplementation of Bos indicus-Influenced Beef Cattle under Tropical Savanna Conditions on Growth Performance, Carcass Characteristics, and Meat Quality.
The effects of castration, supplementation, and implant protocol (IP) on growth, carcass characteristics, and meat quality of grass-fed cattle were evaluated. Two experiments followed a two-way ANOVA and a 2 × 2 factorial arrangement. Experiment-I, 99 bulls were evaluated for: (a) supplementation (mineral (MS) or strategic protein-energy supplementation (SS), and (b) IP (repeated (day-0 and day-90) Zeranol-72 mg implantation (Zeranol-Zeranol) or Trenbolone Acetate-140 mg/Estradiol-20 mg (day-0) followed by Zeranol-72 mg (day-90) (TBA/E2-Zeranol). Experiment II, 50 animals were evaluated for: (a) IP (like Experiment-I), and (b) male class (steers vs. bulls). In Experiment-I, SS bulls had greater growth rate, carcass yield, and yield of high-valued boneless lean cuts than MS bulls, while decreasing (p < 0.05) time to harvest. Steaks from SS-bulls on TBA/E2-Zeranol IP were more (p = 0.05) tender than SS/Zeranol-Zeranol counterparts. Experiment-II bulls had greater growth than steers, but decreased (p < 0.05) carcass quality aspects. Zeranol-Zeranol increased (p < 0.01) meat tenderness of steers. Interactions (p < 0.05) affected cutability (Experiment-II) and meat sensory traits (Experiment-I/II). The SS improved growth, carcass yield, and shortened days until harvest of bulls, while TBA/E2-Zeranol IP positively affected tenderness in bull meat only. Castration improved carcass quality while the implant effects on cutability and tenderness were male-class dependent.


New lipoxygenase inhibitors isolated from Chinese plants. Development of new anti-allergic drugs.
Some natural compounds isolated from Chinese plants were found to have strong inhibitory activity for 5-lipoxygenase and were thus able to inhibit leucotriene synthesis. Among these compounds, caffeic acid was selected for study; more than 100 of its derivatives were synthesized and tested for 5-lipoxygenase inhibitory activity. Two derivatives, TMK-919 and TMK-920, proved to be 100 times more potent than the parent compound and were able to inhibit the homologous PCA reaction significantly in rats at a dose of 10 mg/kg, i.v.


Filling in the gaps: SNX-RGS proteins as multiorganelle tethers.
SNX-RGS proteins are molecular tethers localized to multiple interorganelle contact sites that exhibit roles in cellular metabolism. Here, we highlight recent findings on these proteins and discuss their emerging roles in metabolism, human disease, and lipid trafficking.


RANK ligand as a therapeutic target for bone metastases and multiple myeloma.
Osteoclastic bone resorption is a critical component of skeletal complications of malignancy including fracture, bone pain, hypercalcemia, and spinal cord compression. Three proteins, RANKL, RANK, and OPG have been recently identified as key determinants of osteoclastogenesis and the regulation of bone resorption. Both RANKL and OPG can be aberrantly regulated in the cancer setting and function as important gatekeepers of tumor-induced osteolytic bone disease. RANKL-induced osteoclastogenesis not only mediates osteolytic bone disease, but also contributes to the pathogenesis of osteoblastic bone disease resulting from tumors. In addition, an important role was recently described for bone marrow derived RANKL to mediate the bone-specific tropism of RANK-expressing tumor cells. This manuscript will review how RANKL contributes to skeletal complications of cancer and the development of targeted, mechanism-based drugs that inhibit RANKL.


A single-institutional analysis of racial disparities in clinicopathologic characteristics, treatment selections, and outcomes in advanced-stage pancreatic cancer patients.
To investigate racial disparities among unresectable/metastatic pancreatic ductal adenocarcinoma (PDA) patients treated with contemporary chemotherapy regimens at an urban center. Retrospective review of all PDA patients treated at a single institution between 2012-2017. Continuous and categorical variables were tested using t-test, Mann-Whitney U, chi-squared or Fisher's exact test as appropriate. Kaplan-Meier curves were generated and Cox proportional hazards models were used to analyze survival outcomes. One hundred and forty-five patients identified as: White [69], African American (AA, 34), Asian [15], and Other [27]. Fifty-five-point-seven percent of patients received gemcitabine-based therapy vs. 36.6% received fluorouracil (5-FU) based therapy, specifically 26.1% received FOLFIRINOX and 43.7% received gemcitabine/nab-paclitaxel. In a univariable model, Asians had significantly worse overall survival (OS) than Whites [hazard ratio (HR) 2.74, P=0.013], but there were no OS differences between AA vs. Whites (HR 1.51, P=0.297) nor Other vs. Whites (HR 2.05, P=0.062). On multivariable analysis, Asians had worse OS compared to Whites (HR 2.62, P=0.018), and gemcitabine-based therapy was inferior to 5-FU-based therapy (HR 2.65, P=0.005). There were no OS differences between AA vs. Whites nor Other vs. Whites (HR 1.12, P=0.769 and HR 0.8, P=0.763, respectively). In this series of advanced PDA patients treated with contemporary chemotherapy, AA and White patients had comparable outcomes, but Asians had worse OS than White patients.


Gating and permeation of kainate receptors: differences unveiled.
Kainate receptors (KARs) represent, together with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl D-aspartate (NMDA) receptors, one of the three families of ionotropic glutamate receptors. Recent advances in the study of their biophysical properties have revealed a surprising diversity. KAR-mediated excitatory postsynaptic currents (EPSCs) are often much slower than AMPA receptor-mediated EPSCs, and this is probably due to the slow deactivation rate of KARs containing the GluK4 or GluK5 subunits. By contrast, GluK3-containing receptors, unlike other AMPA/kainate receptors, desensitize faster at low agonist concentrations, making these receptors insensitive to glutamate spillover from neighboring synapses. Moreover, KARs have a wide range of sensitivities to intracellular polyamines and consequently of voltage dependent activation. Finally, newly discovered associated proteins, such as Neto1 and 2, have marked effects on receptor properties, increasing further the potential diversity of KAR functional properties. Altogether, this functional diversity of KARs could have profound consequences on their ability to shape synaptic transmission under physiological and pathological conditions.


Intermittent and continuous exposure to 1,25(OH)2D3 have different effects on growth plate chondrocytes in vitro.
Intermittent 1,25(OH)2D3 administration is widely used to suppress parathyroid glands in secondary (renal) hyperparathyroidism. It is unknown whether the effects of continuous and intermittent 1,25(OH)2D3 differ on vitamin D target organs other than parathyroids. Using primary cultures of rat chondrocytes (tibia) we compared the effects of continuous versus intermittent exposure to physiologic concentrations of 1 alpha,25(OH)2D3 on proliferation (radiothymidine incorporation), cell count, protein synthesis ([3H]-leucine incorporation), alkaline phosphatase activity (as a marker of differentiation) and 1 alpha,25(OH)2D3 receptor (VDR) regulation. Cells were synchronized and then exposed for variable periods to a medium containing 10% delipidated FCS and 10(-8) M to 10(-12) M 1 alpha,25(OH)2D3 (or 1 beta,25(OH)2D3 as specificity control). Intermittent (8 hr exposure every 48 hr) as well as continuous (sham washing) administration of 1 alpha,25(OH)2D3 had a biphasic effect on proliferation, that is, stimulation at low (10(-12) M) and inhibition at high (10(-8) M) concentrations. At 10(-12) M intermittent 1 alpha,25(OH)2D3 yielded higher cell counts than continuous 1,25(OH)2D3. This was seen in the log phase, which was day 3 (continuous 141 +/- 2.3% of solvent control; intermittent 185 +/- 2.0%) and in the plateau phase of growth, which was day 6 (128 +/- 2.6 vs. 169 +/- 2.7% of solvent control). Dependence on extracellular Ca is suggested by the effects of varying nominal Ca concentrations in the medium and of Ca channel blockers. Even two hours of exposure to 1 alpha,25(OH)2D3 (10(-12) M) yielded maximal activation of AP during postincubation.(ABSTRACT TRUNCATED AT 250 WORDS)


Does the addition of drugs targeting the vascular endothelial growth factor pathway to first-line chemotherapy increase complete response? A meta-analysis of randomized clinical trials.
Drugs targeting the vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling (anti-VEGF/VEGFR drugs) are the most validated anti-angiogenic strategies for cancer treatment. Complete response (CR) is a rare event in cancer patients receiving chemotherapy. A meta-analysis was conducted to determine whether adding anti-VEGF/VEGFR drugs to chemotherapy can further increase the chance of CR in the first-line therapy. Relevant databases were systematically searched for the period 2000-2015. Eligible studies were selected according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The incidence, relative risk (RR), and 95 % confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. A total of 12,453 patients from 28 randomized controlled trials were included. The overall incidence of CR in patients treated with anti-VEGF/VEGFR drugs plus chemotherapy was 1.5 % (95 % CI, 1.0-2.0 %) compared to 1.1 % (95 % CI, 0.7-1.4 %) in the chemotherapy-alone arm. Adding anti-VEGF/VEGFR drugs was associated with significant improvement of CR (RR, 1.52, 95 % CI, 1.18-1.95, P = 0.001). When stratified by drug type, adding VEGFR tyrosin kinase inhibitors (TKIs) did not increase the chance of CR (RR, 0.87, 95 % CI, 0.51-1.49; P = 0.614). The addition of bevacizumab with 7.5 mg/kg every 3 weeks, but not 15 mg/kg every 3 weeks, significantly improves the CR (7.5 mg, RR, 2.43, 95 % CI, 1.64-3.60, P = 0.000; 15 mg, RR, 1.07, 95 % CI, 0.63-1.81, P = 0.799). In subgroup analysis, a significant improvement of CR by the addition of anti-VEGF/VEGFR drugs was observed in patients with colorectal cancer (RR, 2.10, 95 % CI 1.21-3.63, P = 0.008), ovarian cancer (RR, 3.07; 95 % CI, 1.68-5.62, P = 0.000), and patients who are treated with platinum-based regimens (RR, 1.78, 95 % CI, 1.23-2.59, P = 0.002). Low-dose bevacizumab, rather than VEGFR TKIs or high-dose bevacizumab, can increase the chance of CR in patients receiving chemotherapy.


Cervicofacial and mediastinal emphysema following minor dental procedure: a case report and review of the literature.
Subcutaneous cervical emphysema is a clinical sign associated with many conditions, including laryngotracheal trauma, pneumothorax and necrotizing deep tissue infections. We discuss a case of a 76-year-old man presenting with extensive cervical emphysema a few hours after a minor dental filling procedure. The CT-scan revealed a significant amount of air within the cervical and mediastinal spaces, reaching lobar bronchi. Vitals were within normal values Bloodwork demonstrated an elevation of creatinine kinase (3718; normal < 150) and mild leukocytosis (WBC = 11.6). We decided to proceed to an urgent cervical exploration to exclude necrotizing fasciitis. This revealed air but no tissue necrosis nor abnormal fluid. The patient improved clinically and was discharged two days later with oral antibiotics. Although cervicofacial subcutaneous emphysema following dental procedures has been reported, it is usually less extensive and involving more invasive procedures using air-driven handpieces. As an otolaryngologist confronted with extensive subcutaneous emphysema following a potential entry route for an aggressive infection, given the seriousness of this diagnosis, the decision of whether or not to perform a diagnostic surgical exploration should remain.


Face off: searching for truth and beauty in the clinical encounter. Based on the memoir, autobiography of a face by Lucy Grealy.
Based on Lucy Grealy's memoir, Autobiography of a Face, this article explores the relationship between gender and illness in our culture, as well as the paradox of "intimacy without intimacy" in the clinical encounter. Included is a brief review of how authenticity, vulnerability, and mutual recognition of suffering can foster the kind of empathic doctor-patient relationship that Lucy Grealy sorely needed, but never received. As she says at the end of her memoir, "All those years I'd handed my ugliness over to people, and seen only the different ways it was reflected back to me."


Efficacy of resuscitative endovascular balloon occlusion of the aorta for hemorrhage control in patients with abnormally invasive placenta: a historical cohort study.
Patients with abnormally invasive placenta (AIP) are at high risk of massive postpartum hemorrhage. Resuscitative endovascular balloon occlusion of the aorta (REBOA), as an adjunct therapeutic strategy for hemostasis, offers the obstetrician an alternative for treating patients with AIP. This study aimed to evaluate the role of REBOA in hemorrhage control in patients with AIP. This was a historical cohort study with prospectively collected data between January 2014 to July 2021 at a single tertiary center. According to delivery management, 364 singleton pregnant AIP patients desiring uterus preservation were separated into two groups. The study group (balloon group, n = 278) underwent REBOA during cesarean section, whereas the reference group (n = 86) did not undergo REBOA. Surgical details and maternal outcomes were collected. The primary outcome was estimated blood loss and the rate of uterine preservation. A total of 278 (76.4%) participants experienced REBOA during cesarean section. The patients in the balloon group had a smaller blood loss during cesarean Sect. (1370.5 [752.0] ml vs. 3536.8 [1383.2] ml; P < .001) and had their uterus salvaged more often (264 [95.0%] vs. 23 [26.7%]; P < .001). These patients were also less likely to be admitted to the intensive care unit after delivery (168 [60.4%] vs. 67 [77.9%]; P = .003) and had a shorter operating time (96.3 [37.6] min vs. 160.6 [45.5] min; P < .001). The rate of neonatal intensive care unit admission (176 [63.3%] vs. 52 [60.4%]; P = .70) and total maternal medical costs ($4925.4 [1740.7] vs. $5083.2 [1705.1]; P = .13) did not differ between the two groups. As a robust hemorrhage-control technique, REBOA can reduce intraoperative hemorrhage in patients with AIP. The next step is identifying associated risk factors and defining REBOA inclusion criteria to identify the subgroups of AIP patients who may benefit more.


Protective effect of Lizhong Pill on nonsteroidal anti-inflammatory drug-induced gastric mucosal injury in rats: Possible involvement of TNF and IL-17 signaling pathways.
The traditional Chinese medicine formula Lizhong Pill (LZP) and its herbal constituents are frequently utilized in Asian (China, Saudi Arabia, India, Japan, etc.) and some European (Russia, Sweden, UK, etc.) nations to treat various gastrointestinal ailments. This study aimed to investigate the protective impact and potential mechanism of LZP against indomethacin (IND)-induced gastric mucosal injury in rats. Using a biochemical kit, we investigated the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) in rat serum, as well as pepsin in rat stomach tissue, using an IND-induced rat model of gastric mucosal injury. Various imaging tools, including HE staining, scanning electron microscopy (SEM), and transmission electron microscopy (TEM), were used to examine the gastric mucosa's surface morphology and ultrastructure. Furthermore, molecular docking was employed to predict the binding capacity of the primary bioactive components of LZP to the critical molecular protein targets in the IL-17 and TNF signaling pathways. At the same time, immunofluorescence was used to determine the protein expressions of CASP3, VCAM1, MAPK15, MMP3, IL-17RA, and TNFR1. The present study demonstrates that LZP (3.75 and 7.50 g/kg) significantly reduces the gastric mucosal injury index induced by IND. This effect is evidenced by the improved morphology, surface, and structure of the gastric mucosa, as determined by HE, SEM, and TEM findings. Additionally, 3.75 and 7.50 g/kg LZP intervention significantly increased SOD and CAT contents and inhibited pepsin and GST activities. Molecular docking analysis revealed that the small molecular components of LZP can bind spontaneously to crucial proteins involved in the IL-17 and TNF signaling pathways, including MAPK15, MMP3, VCAM1, and CASP3. The immunofluorescence findings proved that LZP (3.75 and 7.50 g/kg) can inhibit the protein expressions of MAPK15, MMP3, VCAM1, CASP3, IL-17RA, and TNFR1. Our investigation findings demonstrate that LZP can potentially ameliorate IND-induced damage to the gastric mucosa by inhibiting IL-17 and TNF signaling pathways. These results offer encouraging support for using alternative medicine to manage drug-induced gastric mucosal injury.


The morphologic and morphometric features of the triquetrum.
Fractures of the triquetrum are the second most common form of isolated carpal bone fracture after the scaphoid. However, data on triquetrum morphology and morphometry are sparse. The aim of this study was to describe the morphology of triquetrum using anatomical landmarks, evaluate its morphometric features, and determine its vascular entry points. The morphological and morphometrical features of 87 adult dry triquetral bones (39 left, 48 right) were determined by measuring length, width and thickness. The number and locations of nutrient foramina wider than 0.5 mm were recorded. Mean length, width and thickness were 17.37 mm (range, 14.26-22.13), 12.65 mm (range, 10.37-15.85) and 11.41 mm (range, 8.98-18.23), respectively. The facet articulating with the pisiform was oval in 40 bones, round in 8 and amorphous (neither round nor oval) in 39. The mean length of the interarticular ridge was 7.09 ± 0.9 mm. The mean number of nutrient foramina was significantly greater on the dorsal than on the other aspects. The dorsal predominance of nutrient foramina makes the bone weaker in the dorsal region, which could explain why fractures are more common in this region. Also, the dorsal aspect is rich in blood supply, which could explain why avascular necrosis is less common in triquetral fractures. As most of the vascularization is on the dorsal side, there is need for caution when performing triquetrum surgery. LEVEL OF EVIDENCE: Level 2.


Pure primary squamous cell carcinoma of the breast: a rare presentation and clinicopathologic comparison with usual ductal carcinoma of the breast.
Pure and primary squamous cell carcinomas of the breast are exceedingly uncommon lesions. To the best of our knowledge, based up on review of the literature, only four studies of patients with these tumors, which presented clinically as breast abscess, have been reported previously. We present a woman who sought medical attention for breast pain and was initially diagnosed with a breast abscess. When she did not respond to antibiotic therapy, an incision as well as drainage was performed. Histologic examination of the material revealed a pure squamous cell carcinoma. An extensive work up ruled out other primary sites. She was treated with mastectomy and radiation therapy and has seen disease-free 3 years postdiagnosis. We also review the literature for presenting features, value of imaging studies, role of cytology in diagnosis, and therapy of such tumors in comparison to the usual ductal carcinomas of the breast.