Technical report: surgical preparation of human brain tissue for clinical and basic research.
The study of the distinct structure and function of the human central nervous system, both in healthy and diseased states, is becoming increasingly significant in the field of neuroscience. Typically, cortical and subcortical tissue is discarded during surgeries for tumors and epilepsy. Yet, there is a strong encouragement to utilize this tissue for clinical and basic research in humans. Here, we describe the technical aspects of the microdissection and immediate handling of viable human cortical access tissue for basic and clinical research, highlighting the measures needed to be taken in the operating room to ensure standardized procedures and optimal experimental results. In multiple rounds of experiments (n = 36), we developed and refined surgical principles for the removal of cortical access tissue. The specimens were immediately immersed in cold carbogenated N-methyl-D-glucamine-based artificial cerebrospinal fluid for electrophysiology and electron microscopy experiments or specialized hibernation medium for organotypic slice cultures. The surgical principles of brain tissue microdissection were (1) rapid preparation (<1 min), (2) maintenance of the cortical axis, (3) minimization of mechanical trauma to sample, (4) use of pointed scalpel blade, (5) avoidance of cauterization and blunt preparation, (6) constant irrigation, and (7) retrieval of the sample without the use of forceps or suction. After a single round of introduction to these principles, multiple surgeons adopted the technique for samples with a minimal dimension of 5 mm spanning all cortical layers and subcortical white matter. Small samples (5-7 mm) were ideal for acute slice preparation and electrophysiology. No adverse events from sample resection were observed. The microdissection technique of human cortical access tissue is safe and easily adoptable into the routine of neurosurgical procedures. The standardized and reliable surgical extraction of human brain tissue lays the foundation for human-to-human translational research on human brain tissue.


Effects of biowaste-derived biochar on the dynamic behavior of cadmium fractions in soils.
As a commonly used amendment to soil contaminated by heavy metals, biochar has attracted great attention and has been applied for decades due to the benefits to the soil. However, the effects of biochar on the dynamic behavior of soil properties and metal fractions are still unclear. Here, we used two biochars, derived from biowastes (reed and bamboo willow), to treat two cadmium (Cd)-contaminated soils, S1 (loamy sand) and S2 (sandy loam), and determined the dynamic effects. The incubation experiments were designed to investigate the effects of biochar on the dynamic behavior of soil pH, dissolved organic matter (DOM), bioavailable Cd, and the transformation of Cd fractions for 270 days. The results showed that the soil pH, DOM, and bioavailable Cd initially increased and then decreased with incubation time, and the soil pH and DOM were higher, but bioavailable Cd content was lower than the original value. The transformation of the metal fractions changed dynamically, and the exchangeable fraction of Cd decreased with incubation time. Furthermore, the correlation results showed that the DOM can directly control the redistribution of Cd fractions, while soil pH can control it indirectly by regulating the DOM. This study highlighted that biochar can affect soil pH and DOM, redistribute Cd fractions, decrease bioavailable Cd content, and lower the potential risk of heavy metals. This study suggests ways to immobilize heavy metals in contaminated soils using biochar.


Acquired intra abdominal testis due to adhesions after necrotizing enterocolitis.
Undescendent testis happens usually due to the stagnation during testicular descends. Stagnation of a testicle in the abdomen may be the target of adhesions with intestinal segments. Our case report a very rare variant of acquired intra-abdominal cryptorchidism due to adhesions after necrotizing enterocolitis. Newborn baby after NEC has a significant risk of developing intraperitoneal adhesions. In this report we will describe a case of previously palpable testis in the inguinal canal at neonatal age which was pulled inside the abdomen at seventh month of age through adhesions between test and the segment of sigmoid colon after NEC.


BRAF Modulates Lipid Use and Accumulation.
There is increasing evidence that oxidative metabolism and fatty acids play an important role in BRAF-driven tumorigenesis, yet the effect of BRAF mutation and expression on metabolism is poorly understood. We examined how BRAF mutation and expression modulates metabolite abundance. Using the non-transformed NIH3T3 cell line, we generated cells that stably overexpressed BRAF V600E or BRAF WT. We found that cells expressing BRAF V600E were enriched with immunomodulatory lipids. Further, we found a unique transcriptional signature that was exclusive to BRAF V600E expression. We also report that BRAF V600E mutation promoted accumulation of long chain polyunsaturated fatty acids (PUFAs) and rewired metabolic flux for non-Warburg behavior. This cancer promoting mutation further induced the formation of tunneling nanotube (TNT)-like protrusions in NIH3T3 cells that preferentially accumulated lipid droplets. In the plasma of melanoma patients harboring the BRAF V600E mutation, levels of lysophosphatidic acid, sphingomyelin, and long chain fatty acids were significantly increased in the cohort of patients that did not respond to BRAF inhibitor therapy. Our findings show BRAF V600 status plays an important role in regulating immunomodulatory lipid profiles and lipid trafficking, which may inform future therapy across cancers.


Circadian variation of food intake and digestive tract contents in the rat.
The variation of food intake and digestive tract contents over a period of 24 hours was measured in the free feeding rat kept under a 12:12 hr light:dark cycle (lights on at 0700 hr). After a cessation between 0700 and 1000 hr, the rate of food intake increased progressively during daytime followed by a marked increase and a plateau after lights went off. In the dark, dry matter in the stomach was almost ten times the levels of the light phase. In the major part of the high feeding period, the rates of food intake and gastric emptying equilibrated. Dry matter content of the intestine also followed circadian variations that were specific for each segment. The time-to-time content of the mid-gut segment was closely related to gastric emptying. The extent of dry matter absorption in the proximal intestine decreased continuously from the time lights went on and reached a minimum at 22 hr. Absorption in the distal segments was much less subjected to variation over 24 hours. In the free feeding situation, the changes induced by the light cycle on the rhythm of food intake were accompanied by marked modifications of digestive tract contents including those of the intestine. Data indicate a close relationship between gastric function and the middle portion of the intestine.


HOT mutation screening in human glioblastomas.
Somatic mutations in IDH1 and IDH2 are described in glioblastomas (GBMs). Mutant IDH1 and IDH2 reduce α-KG to D-2HG which accumulates, and is proposed to promote tumorigenesis. HOT catalyzes the conversion of γ-hydroxybutyrate to succinic semialdehyde in a reaction that produces D-2HG. Since increased HOT enzyme activity could lead to an accumulation of D-2HG, coupled with the fact that only a minority of GBMs carry IDH1/2 mutations and 2HG accumulation has recently been described in IDH wild-type tumors, we analyzed a set of GBM samples for mutations in the HOT gene. We screened 42 human GBM samples for mutations in HOT. No mutations in HOT were identified in the 42 GBM samples screened. Mutations in the coding regions of HOT do not occur at an appreciable frequency in GBM.


Distribution and reuse of 76Se-selenosugar in selenium-deficient rats.
Nutritional selenium compounds are transformed to the common intermediate selenide and then utilized for selenoprotein synthesis or excreted in urine mostly as 1beta-methylseleno-N-acetyl-Dd-galactosamine (selenosugar). Since the biological significance of selenosugar formation is unknown, we investigated their role in the formation of selenoenzymes in selenium deficiency. Rats were depleted of endogenous natural abundance selenium with a single stable isotope ((82)Se) and then made Se-deficient. (76)Se-Selenosugar was administered intravenously to the rats and their urine, serum, liver, kidneys and testes were subjected to speciation analysis with HPLC inductively coupled argon plasma mass spectrometry. Most (76)Se was recovered in its intact form (approximately 80% of dose) in urine within 1 h. Speciation analysis revealed that residual endogenous natural abundance selenium estimated by (77)Se and (78)Se was negligible and distinct distributions of the labeled (76)Se were detected in the body fluids and organs without interference from the endogenous natural abundance stable isotope. Namely, intact (76)Se-selenosugar was distributed to organs after the injection, and (76)Se was used for selenoprotein synthesis. Oxidation to methylseleninic acid and/or hydrolysis of the selenoacetal group to methylselenol were proposed to the transformation of selenosugar for the reuse. Effective use of an enriched stable isotope as an absolute label in hosts depleted of natural abundance isotopes was discussed for application in tracer experiments.


Necrotizing fasciitis caused by Haemophilus influenzae type b in a patient with rectal cancer treated with combined bevacizumab and chemotherapy: a case report.
Recently, necrotizing fasciitis has been reported in patients treated with bevacizumab, usually secondary to wound healing complications, gastrointestinal perforations, or fistula formation. The risk of invasive Haemophilus influenzae type b infection is significantly increased in immunocompromised hosts. However, necrotizing fasciitis due to Haemophilus influenzae type b in a patient treated with combined bevacizumab and chemotherapy has not been previously reported. A 59-year-old woman was admitted to the intensive care unit after sudden onset of fever, chills, and right thigh pain. She received chemotherapy with fluorouracil, irinotecan, and bevacizumab for colon cancer 10 days prior to admission. The advancing erythematous margin and her worsening clinical condition prompted us to suspect necrotizing fasciitis and consult the orthopedics department for a fascia biopsy and debridement. Surgical exploration revealed a murky dishwater-colored pus exudate from the incision site and the lack of a shiny appearance of the fascia that also suggested necrotizing fasciitis. After 2 days, the final results of the blood and exudate cultures confirmed the presence of Haemophilus influenzae type b. A diagnosis of necrotizing fasciitis due to Haemophilus influenzae type b was made. The patient required recurrent surgical debridement and drainage, but she recovered from the septic shock. We report a case of necrotizing fasciitis due to Haemophilus influenzae type b in a patient without injury and with rectal cancer treated with combined bevacizumab and chemotherapy. Physicians should consider invasive Haemophilus influenzae type b disease in the presence of necrotizing fasciitis in patients treated with this combined treatment modality.


Non-invasive diagnosis of congenital coronary arteriovenous fistula by cross-sectional and Doppler echocardiography.
A four-year-old child is reported in whom diagnosis of right coronary arteriovenous fistula draining into the right ventricle was made non-invasively, using cross-sectional and Doppler echocardiography. It was confirmed subsequently by coronary arteriography and surgery.


Distant metastases in papillary thyroid cancer. A review of 91 patients.
Of 731 patients with papillary thyroid cancer, 91 had metastases outside regional lymph nodes. The most common site was intrathoracic, occurring in 73 of the 91 patients. Miliary, micronodular pulmonary metastases, with iodine 131 (I-131) uptake and "curable" by I-131 treatment were encountered in seven patients. It has not been established whether this was a transient stage in additional patients. In 38 patients rounded, macronodular pulmonary metastases were found. Another 21 patients had unilateral pulmonary infiltration and mediastinal enlargement. Pulmonary infiltrations may be hematogenic, or may possibly occur via regional, mediastinal lymph nodes. Mortality within 1 year of the diagnosis of distant metastases exceeded 50%. Occurrence of distant metastases showed a slight but highly significant association with male sex, advanced age, and advanced local tumor stage. Better prognostic determinants are, however, required if adequate of the individual patient with papillary thyroid cancer is to be achieved.


Role of the nuclear envelope in the pathogenesis of age-related bone loss and osteoporosis.
The nuclear envelope is the most important border in the eukaryotic cell. The role of the nuclear envelope in cell differentiation and function is determined by a constant interaction between the elements of the nuclear envelope and the transcriptional regulators involved in signal transcription pathways. Among those components of the nuclear envelope, there is a growing evidence that changes in the expression of A-type lamins, which are essential components of the nuclear lamina, are associated with age-related changes in bone affecting the capacity of differentiation of mesenchymal stem cells into osteoblasts, favoring adipogenesis and affecting the function and survival of the osteocytes. Overall, as A-type lamins are considered as the 'guardians of the soma', these proteins are also essential for the integrity and quality of the bone and pivotal for the longevity of the musculoskeletal system.


Controllable chaos in hybrid electro-optomechanical systems.
We investigate the nonlinear dynamics of a hybrid electro-optomechanical system (EOMS) that allows us to realize the controllable opto-mechanical nonlinearity by driving the microwave LC resonator with a tunable electric field. A controllable optical chaos is realized even without changing the optical pumping. The threshold and lifetime of the chaos could be optimized by adjusting the strength, frequency, or phase of the electric field. This study provides a method of manipulating optical chaos with an electric field. It may offer the prospect of exploring the controllable chaos in on-chip optoelectronic devices and its applications in secret communication.


Association of ERCC family mutations with prognosis and immune checkpoint inhibitors response in multiple cancers.
The proteins encoded by the excision repair cross-complementing (ERCC) family are pivotal in DNA damage repair and maintaining genome stability. However, the precise role of the ERCC family in tumor prognosis and the effectiveness of immune checkpoint inhibitors (ICI) therapy remain uncertain. This study aimed to explore the connection between ERCC mutations and prognosis as well as the response to ICI. We observed that patients with ERCC mutations exhibited enhanced progression-free survival (PFS) and overall survival (OS) in two independent pan-cancer cohorts. Furthermore, this mutant subgroup showed higher tumor mutation burden (TMB) compared to the wild-type subgroup. Notably, ERCC mutations were associated with better OS (HR 0.54, 95% CI 0.42-0.70; P < 0.001) in pan-cancer patients who underwent ICI therapy (N = 1661). These findings were validated in a separate cohort, where patients in the ERCC mutant subgroup demonstrated improved clinical outcomes (HR 0.56, 95% CI 0.37-0.84; P = 0.03) and higher response rates (51.9% vs. 26.8%) than the wild-type subgroup. Further analysis revealed that patients with ERCC mutations displayed elevated tumor neoantigen burden (TNB) levels and increased infiltration of immune-response cells. Our study suggests that ERCC mutations are linked to enhanced immunogenicity and improved ICI efficacy, thus potentially serving as a biomarker for ICI therapy.


Sequential chemotherapy and late intensification for malignant lymphomas of aggressive histologic type.
Fifty-six patients with malignant lymphoma of aggressive histologic type (51 large cell, three diffuse undifferentiated, and two nodular mixed) were treated with three non-cross-resistant combination chemotherapy regimens that were introduced sequentially according to the response to therapy. The objective was to increase the complete remission rate by changing the chemotherapy regimen early if the patient did not attain a complete remission after three courses of treatment. Late intensification was also used with the aim of prolonging the duration of complete remission. The overall complete remission rate obtained with this approach was 82 percent (100 percent in stages I to III and 66 percent in stage IV). The projected survival at four years is 71 percent (93 percent for stages I to III and 55 percent for stage IV). Eighty percent of patients with complete remission are projected to have continued remission at four years. Compared with previous experience with Adriamycin-based combination regimens, these results represent an improvement in remission and survival parameters. The most significant gains occurred in the prolongation of survival of patients with stages I to III disease and in the improved duration of complete remission of patients with stage IV disease. Toxicity included 15 documented infections among 320 courses of therapy, four cases of congestive heart failure, one case of bleomycin lung toxicity, and two cases of liver dysfunction. This multiple combination regimen represents an improvement over previous results utilizing Adriamycin-based combination chemotherapy.


A pilot randomized trial assessing the effects of autogenic training in early stage cancer patients in relation to psychological status and immune system responses.
Autogenic training (AT) is a type of meditation usually used for reducing stress. This pilot study describes how AT was used on a group of early stage cancer patients and the observed effect on stress-related behaviours and immune system responses. This was a randomized trial with 31 early stage breast cancer women, having received a lumpectomy and adjuvant radiotherapy. The women were randomized into two groups. Group 1 received a home visit only. Group 2 received a home visit and 2 months' weekly Autogenic training. At the beginning and end of the 2 monthly periods, the Hospital Anxiety and Depression Scale (HADS) and T and B cell markers were measured to give an indication of changes in immune system responses and measurement of anxiety and depression. At the end of the study, HADS scores and T and B cell markers remained similar in the women who did not receive AT. The women receiving AT showed a strong statistical difference for an improvement in their HADS scores and those women observed in a meditative state as opposed to a relaxed state were found to have an increase in their immune responses. This study suggests AT as a powerful self-help therapy.


Mapping of BnMs4 and BnRf to a common microsyntenic region of Arabidopsis thaliana chromosome 3 using intron polymorphism markers.
A recessive epistatic genic male sterile two-type line, 7365AB (Bnms3ms3ms4msRrfRf/BnMs3ms3ms4ms4RfRf), combined with the fertile interim-maintainer 7365C (Bnms3ms3ms4ms4rfrf) is an effective pollination control system in hybrid rapeseed production. We report an effective strategy used to fine map BnMs4 and BnRf. The two genes were both defined to a common microsyntenic region with Arabidopsis chromosome 3 using intron polymorphism (IP) markers developed according to Arabidopsis genome information and published genome organization of the A genome. The near-isogenic lines 7365AC (Bnms3ms3ms4ms4Rfrf/Bnms3ms3ms4ms4rfrf) of BnRf and 736512AB (Bnms3ms3Ms4ms4RfRf/Bnms3ms3ms4ms4RfRf) of BnMs4 were constructed to screen developed markers and create genetic linkage maps. Nine polymorphic IP markers (P1-P9) were identified. Of these, P2, P3, P4, and P6 were linked to both BnMs4 and BnRf with genetic distances <0.6 cM. Three simple sequence repeat markers, SR2, SR3, and SR5, were also identified by using public information. Subsequently, all markers linked to the two genes were used to compare the micro-collinearity of the regions flanking the two genes with Brassica rapa and Arabidopsis. The flanking regions showed rearrangements and inversion with fragments of different Arabidopsis chromosomes, but a high collinearity with B. rapa. This collinearity provided extremely valuable reference for map-based cloning in polyploid Brassica species. These IP markers could be exploited for comparative genomic studies within and between Brassica species, providing an economically feasible approach for molecular marker-assisted selection breeding, accelerating the process of gene cloning, and providing more direct evidence for the presence of multiple alleles between BnMs4 and BnRf.


Medical surveillance for carpal tunnel syndrome in workers.
Carpal canal size was examined as a risk factor associated with carpal tunnel syndrome in the workplace. Seven of 14 electricians had symptoms of carpal tunnel syndrome. When cross-sectional areas were measured by computed tomography (CT), affected workers had a cross-sectional area of 1.75 +/- 0.21 cm2; control values were 2.53 +/- 0.15 cm2 (p less than 0.05). Subjects with a subclinical syndrome had an area of 1.83 +/- 0.22 cm2, which was similar to the group with symptoms. Wrist circumference was not a predictor of the smallest carpal canal area. Unusual bony and soft tissue structures within the carpal canal were easily identified with CT.


Development and validation of a risk prediction model for overall survival in patients with nasopharyngeal carcinoma: a prospective cohort study in China.
Nasopharyngeal carcinoma (NPC) is prevailing in Southern China, characterized by distinct geographical distribution. Aimed to predict the overall survival (OS) of patients with nasopharyngeal carcinoma, this study developed and validated nomograms considering demographic variables, hematological biomarkers, and oncogenic pathogens in China. The clinicopathological and follow-up data of the nasopharyngeal carcinoma patients obtained from a prospective longitudinal cohort study in the Chongqing University Cancer Hospital between Jan 1, 2017 and Dec 31, 2019 ([Formula: see text]). Cox regression model was used to tested the significance of all available variables as prognostic factors of OS. And independent prognostic factors were identified based on multivariable analysis to model nomogram. Concordance index (C-index), area under the receiver operating characteristic (AUC), calibration curve, and decision curve analysis (DCA) were measured to assess the model performance of nomogram. Data was randomly divided into a training cohort (1227 observers, about 70% of data) and a validation group (408 observers, about 30% of data). At multivariable analysis, the following were independent predictors of OS in NPC patients and entered into the nomogram: age (hazard ratio [HR]: 1.03), stage (stage IV vs. stage I-II, HR: 4.54), radiotherapy (Yes vs. No, HR: 0.43), EBV ([Formula: see text] vs.[Formula: see text], HR: 1.92), LAR ([Formula: see text] vs.[Formula: see text], HR: 2.05), NLR ([Formula: see text] vs. [Formula: see text] HR: 1.54), and PLR ([Formula: see text] vs.[Formula: see text], HR: 1.79). The C-indexes for training cohort at 1-, 3- and 5-year were 0.73, 0.83, 0.80, respectively, in the validation cohort, the C-indexes were 0.74 (95% CI 0.63-0.86), 0.80 (95% CI 0.73-0.87), and 0.77 (95% CI 0.67-0.86), respectively. The calibration curve demonstrated that favorable agreement between the predictions of the nomograms and the actual observations in the training and validation cohorts. In addition, the decision curve analysis proved that the nomogram model had the highest overall net benefit. A new prognostic model to predict OS of patients with NPC was developed. This can offer clinicians treatment making and patient counseling. Furthermore, the nomogram was deployed into a website server for use.


Management of infants with intra-uterine growth restriction.
Intra-uterine growth restriction (IUGR) contributes to almost two-thirds of LBW infants born in India. Poor nutritional status and frequent pregnancies are common pre-disposing conditions in addition to obstetric and medical problems during pregnancy. Growth restriction may be symmetrical or asymmetrical depending on the time of insult during pregnancy. The pathological insult in an asymmetrical IUGR occurs during the later part of the pregnancy and has a brain-sparing effect. Common morbidities are more frequent in < 3rd percentile group as compared to 3rd-10th percentile group. Guidelines for management of IUGR neonates in these two groups have been provided in the protocol.


Hip and knee replacement in patients with ochronosis: Clinical experience and literature review.
Patients with alkaptonuria can present ochronotic degenerative arthropathy due to the accumulation of pigments in the cartilages. Ochronotic arthropathy initially affects the spine, then there is the involvement of the other large joints, with greater frequency of the knees. In this article we will present two patients with alkaptonuria who have been effectively treated with knee and hip replacement, comparing our experience with what is available in the literature.


Motor cortex stimulation for pain control induces changes in the endogenous opioid system.
Motor cortex stimulation (MCS) for neuropathic pain control induces focal cerebral blood flow changes involving regions with high density of opioid receptors. We studied the possible contribution of the endogenous opioid system to MCS-related pain relief. Changes in opioid receptor availability induced by MCS were studied with PET scan and [(11)C]diprenorphine in eight patients with refractory neuropathic pain. Each patient underwent two preoperative (test-retest) PET scans and one postoperative PET scan acquired after 7 months of chronic MCS. The two preoperative scans, performed at 2 weeks interval, did not show significant differences. Conversely, postoperative compared with preoperative PET scans revealed significant decreases of [(11)C]diprenorphine binding in the anterior middle cingulate cortex (aMCC), periaqueductal gray (PAG), prefrontal cortex, and cerebellum. Binding changes in aMCC and PAG were significantly correlated with pain relief. The decrease in binding of the exogenous ligand was most likely explained by receptor occupancy due to enhanced secretion of endogenous opioids. Motor cortex stimulation (MCS) may thus induce release of endogenous opioids in brain structures involved in the processing of acute and chronic pain. Correlation of this effect with pain relief in at least two of these structures supports the role of the endogenous opioid system in pain control induced by MCS.


Prevalence and predictors of dysmenorrhea among a population of adolescent's schoolgirls (Morocco).
Dysmenorrhea is the most common gynaecological problem among young females. In Arabic countries, few studies on gynaecological problems of adolescent's girls were published. the aim of the study was to determine the prevalence of dysmenorrhea and associated factors among adolescents in public schools at Marrakesh. we conducted a cross-sectional study; our data was collected via a questionnaire and the statistical analysis was done using SPSS version 21. Our random sample counted 364 post-menarcheal girls aged between 12 and 20 years who participated voluntarily in our study. the mean age at menarche was 12.89 ± 1.34 years; the prevalence of dysmenorrhea was 78% and 58.1% of them suffering from severe dysmenorrhea that increased clearly with the chronological age. Dysmenorrhea was cause for missing school among 13% of girls and the most common symptoms associated with it were backache, fatigue, irritability and anxiety. The gynecological age was found to be the only predictive factor of dysmenorrhea among schoolgirls. reproductive health education should be improved enough by including them in the school curriculum to prepare girls for menstruation and inform them about problems related to this phenomenon, especially dysmenorrhea.


A novel anti-MUC1 antibody against the MUC1 cytoplasmic tail domain: use in sensitive identification of poorly differentiated cells in adenocarcinoma of the stomach.
Isolated cancer cells of non-solid type poorly differentiated adenocarcinoma (por2) or signet-ring cell carcinoma (sig) are frequently seen in scirrhous gastric cancers with a very poor prognosis. These cells are often scattered in granulation tissue or desmoplastic fibrotic tissue and tend to be overlooked in routine pathological examination. We aimed to raise a novel antibody that can identify the isolated cancer cells easily. Because the MUC1 cytoplasmic tail domain (CTD) has many biological roles including tumor progression and cell adhesion disturbance and is expected to be expressed in isolated cancer cells, we raised a novel monoclonal antibody (MAb) MUC1-014E against an intracellular nonrepeating 19-amino-acid sequence (RYVPPSSTDRSPYEKVSAG: N-1217-1235-C) of the MUC1 CTD, using a synthetic peptide including the 7-amino-acid epitope (STDRSPY: N-1223-1229-C). In the immunohistochemical staining of 107 gastrectomy specimens including 48 por2 and 31 sig lesions, the MAb MUC1-014E showed high rates of positive staining (≥5% of carcinoma cells stained) for por2 (100%) and sig (97%), and of the highest intensity staining (4+, ≥75% of carcinoma cells stained) for por2 (100%) and sig (90%). In the 89 biopsy specimens including 82 por2 and 38 sig lesions, the MAb MUC1-014E showed high rates of positive staining for por2 (100%) and sig (100%) and of 4+ staining for por2 (87%) and sig (84%). All the rates were significantly higher than those with cytokeratins (AE1/AE3 or CAM5.2). The MAb MUC1-014E is very useful for accurate detection of isolated cancer cells in scirrhous gastric cancers.


Lipase-catalyzed selective synthesis of monolauroyl maltose using continuous stirred tank reactor.
Monolauroyl maltose was synthesized by an immobilized lipase that catalyzed condensation of maltose and lauric acid in acetone using a batch reactor or a continuous stirred tank reactor. Mono- and di-lauroyl maltoses were identified by FT-IR, (1)H NMR, (13)C NMR and MS. Monolauroyl maltose was selectively synthesized in a continuous stirred tank reactor and no diester was detected. The highest concentration of monolauroyl maltose at 28 mmol/l was obtained in 250 ml acetone when maltose was added at 4 g/d and the molar ratio of lauric acid to maltose was fixed at 4:1 at a flow rate of 0.15 ml/min for both influx and effluent without supplement of fresh molecular sieve.


Instruments for measuring patient safety competencies in nursing: a scoping review.
Patient safety competencies in nursing are essential for the quality of healthcare. To develop practices and collaboration in nursing care, valid instruments that measure competencies in patient safety are needed. To identify instruments that measure the patient safety competencies of nurses. A scoping review. The Cochran Library, Epistemonikos, Eric, Ovid Medline, CINAHL, Embase and Web of Science databases were searched for articles reporting on instruments measuring patient safety competence in nursing. The search was limited to English peer-reviewed scientific papers published from January 2010 to April 2021. A blinded selection of articles fulfilling the inclusion criteria was performed by two researchers based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Data were then extracted, synthesised and presented in tables and text. Our search identified 1,426 papers, of which 32 met the inclusion criteria. The selected papers described nine instruments, of which the 'Health Professional Education in Patient Safety Survey' was the most used instrument. The identified instruments comprised domains for patient safety skills, attitudes, knowledge, communication, teamwork and errors. The instruments had been tested for content (face) and construct validity as well as for reliability. However, sensitivity and responsiveness were rarely assessed. Over the last decade, there has been a growing body of instruments aimed at measuring patient safety competencies among nurses. The future development of new instruments should consider including the important dimension of ethics in patient safety as well as evaluating the instrument's responsiveness to be able to track changes over time.


Emerging vaccines for influenza.
Influenza remains one of the leading causes of morbidity and mortality worldwide. The available vaccines are least effective in the populations at greatest risk--children, the elderly, and the immunocompromised. Furthermore, avian influenza and other novel strains have the potential to cause the next influenza pandemic. Research efforts have accelerated worldwide to develop new vaccines to provide better immunity against annual epidemics and a potential pandemic. To summarize the global research efforts at developing new influenza vaccines, adjuvants, and delivery devices. MEDLINE and Pharmaprojects databases were searched for publications and continuing research on new influenza vaccine technologies. Technologies such as DNA vaccines, live recombinant viral vector vaccines, and virus-like particles have shown significant promise for immunogenicity and protection from experimental challenge to influenza. New modalities for vaccine delivery and methods for rapid vaccine production are also being investigated. With the possibility of an influenza pandemic increasing the need to develop new vaccines, the global research community has made large strides to meet this challenge.


The consequences of long-time arm morbidity in node-negative breast cancer patients with sentinel node biopsy or axillary clearance.
The aim was to evaluate long-time morbidity in breast cancer patients 3 years after sentinel node biopsy (SNB) or axillary clearance (AC) emphasizing the consequences of morbidity like work-related events and the need of physiotherapy. Morbidity was evaluated in 92 breast cancer patients 3 years after SNB only and in 47 patients after AC using a questionnaire. The circumferences of the upper extremities and the range of the shoulder movements were also measured. Two SNB and eight AC patients were not able to use the ipsilateral upper extremity to former extent P < 0.005. One SNB and one AC patient were retired or on a long-time sick leave because of arm morbidity. Clinically apparent upper extremity lymphoedema was observed in one SNB patient and in six AC patients, P < 0.005. Two SNB patients had received manual lymph drainage, one of them because of breast oedema. Seven patients had received manual lymph drainage after AC, three of them wore also compression sleeve, P < 0.05 between AC and SNB. The risk of remarkable long-time arm morbidity after SNB is minimal. Work-related events seem uncommon due to arm morbidity, regardless of the extent of axillary surgery.


Impact of emergency department visit on disease self-management in adults with depression.
Unexpected health-endangering events that lead to an emergency department visit may be perceived as "wake-up calls" and induce significant changes in health-related behavior ("health shock" effect). This study uses two waves of a survey of 826 adults with depression and finds that having an emergency department visit(s) increased medication adherence by 7.6 percentage points ( p < 0.05) relative to non-emergency department visitors but had no significant effect on counseling attendance (0.02% points, p = 0.380). Emergency department visits may provide an opportune teachable moment to initiate targeted interventions for positive behavioral change in adults with depression.


P300 and time of day: circadian rhythms, food intake, and body temperature.
The P300 or P3 component of the event-related brain potential (ERP) was obtained from five groups of 24 young adult subjects, with each group measured at a different time of day (8 a.m., 11 a.m., 2 p.m., 5 p.m., 8 p.m.). An activity-preference questionnaire was used to ensure that an equitable number of morning- and evening-preferring subjects were obtained for each testing time. P3 measures, physiological (body temperature, heart rate, subjective alertness), and cognitive performance (digit span, prose memory, digit symbol) variables were assessed. P3 amplitude and latency were not affected directly by the time of day. However, P3 amplitude was smaller in subjects who had not eaten within 6 hours of testing relative to subjects who had a recent meal, and P3 latency was correlated negatively with body temperature. The findings suggest that although the P3 ERP is not influenced by circadian rhythms, it is related to recency of food intake and physiological factors which change with time of day.


Cardiac tamponade following penetrating thoracic trauma: unusual evolution.
We report a case of cardiac tamponade following a penetrating wound of the heart treated surgically. The patient developed later on a pericarditis of the immunologic type complicated by new tamponade. The clinical situation was only relieved by corticotherapy.


Mandibular reconstruction with the Dacron urethane tray: a radiologic assessment of bone remodeling.
A retrospective study was made of 22 consecutive patients who underwent mandibular reconstruction with a Dacron (Osteo-mesh, Xomed Inc, Jacksonville, FL) tray technique from September 1988 to April 1992. Free autogenous iliac bone, in the form of particulate cancellous chips and marrow, was densely packed into the Dacron tray, that was adapted to bridge the mandibular segmental defect. Sixteen cases underwent uneventful healing with the formation of a continuous bony bridge and union with the remaining mandible. The pattern of bone remodeling and rate of resorption in these cases were assessed by sequential panoramic radiographs taken up to 3 years postoperatively. The mean horizontal dimension of the mandibular defects was 75 mm and the mean vertical reconstructed height was 25 mm. When the grafted bone was radiographically of uniform density, it progressed into a mature trabecular pattern matching that of the normal mandible. However, when there were areas of radiolucency, most likely from inadequate condensation of the graft, such areas were not replaced by bone in the long term. The bony height at both ends and the middle of the reconstructed segment underwent reasonably even resorption and retained about 80% of the bony height over a 3-year period. The rate of resorption was highest in the first 6 months and stabilized at about 2 years. There were six failures, all showing significant irregular bony resorption prior to tray removal.


Comparative non-shivering thermogenesis in adjacent populations of the common spiny mouse (Acomys cahirinus) from opposite slopes: the effects of increasing salinity.
We compared non-shivering thermogenesis between two adjacent populations of the common spiny mouse Acomys cahirinus from different habitats, in relation to increasing salinity. Individuals were captured from the north- and south-facing slopes of the same valley, that represent "Mediterranean" and "desert" habitats, respectively. We hypothesized that the two populations of mice would differ in their thermoregulatory capacities, reflecting their need to cope with the environmental stress in each habitat. We measured resting metabolic rate by recording oxygen consumption, body temperature and response to an injection of exogenous noradrenaline. Mice were maintained on diets with increasing levels of salt intake to examine their abilities to cope with increasing osmotic stress. Mice from north-facing slopes generally had a higher resting metabolic rate and a higher increase in oxygen consumption in response to noradrenaline than mice from south-facing slopes. Increasing salinity decreased resting metabolic rate values, body temperature, and oxygen consumption in response to noradrenaline in both populations, and diminished slope-dependant differences. We suggest that these differences could be a result of an ongoing adaptive process to different climatic conditions, typical of the Mediterranean region, that are a demonstrable example of evolution in action.


Diagnostic efficiency of the AUDIT-C in U.S. veterans with military service since September 11, 2001.
Alcohol screening with the 3-item alcohol use disorders identification test (AUDIT-C) has been implemented throughout the U.S. Veterans Health Administration. Validation of the AUDIT-C, however, has been conducted with samples of primarily older veterans. This study examined the diagnostic efficiency of the AUDIT-C in a younger cohort of veterans who served during Operation Enduring Freedom and/or Operation Iraqi Freedom (OEF/OIF). Veteran participants (N=1775) completed the alcohol use disorders identification test (AUDIT) and underwent the structured clinical interview for DSM-IV-TR for Axis I disorders (SCID) in research settings within four VA medical Centers. Areas under receiver operating characteristic curves (AUCs) measured the effiency of the full AUDIT and AUDIT-C in identifying SCID-based diagnoses of past year alcohol abuse or dependence. Both measures performed well in detecting alcohol use disorders. In the full sample, the AUDIT had a better AUC (.908; .881-.935) than the AUDIT-C (.859; .826-.893; p<.0001). It is notable that this same result was found among men but not women, perhaps due to reduced power. Diagnostic efficiency statistics for the AUDIT and AUDIT-C were consistent with results from older veteran samples. The diagnostic efficiency of both measures did not vary with race or age. Both the AUDIT and AUDIT-C appear to be valid instruments for identifying alcohol abuse or dependence among the most recent cohort of U.S. veterans with service during OEF/OIF within research settings.


Hepatic and extrahepatic splanchnic glucose metabolism in the postabsorptive and glucose fed dog.
In awake dogs we measured the glucose balance across the liver and extrahepatic splanchnic tissues in the postabsorptive state and during two hours of IV infusion of glucose or for three hours following ingestion of oral glucose and during four hours of sequential intraportal followed by oral glucose. The IV glucose infusion rate was adjusted to maintain a steady state glucose concentration of either euglycemic levels (insulin clamp, group 1, N = 4), 125 mg/100 mL above the postabsorptive glucose concentration (+125 mg glucose clamp, group 2, N = 3) or 200 mg/100 mL above basal glucose levels (+200 mg glucose clamp, group 3, N = 7). Oral glucose was given at a dose of either 1.5 g/kg (group 4, N = 7) or 2.5 g/kg (group 5, N = 12). In dogs that received IV glucose, basal gut glucose uptake (0.5 +/- 0.1 mg/min X kg) was stimulated by hyperglycemia (1.5 +/- 0.5 and 1.4 +/- 0.1 mg/min X kg for group 2 and 3, respectively, P less than 0.05). In these same animals basal hepatic glucose output (-2.7 +/- 0.3 mg/min X kg) was promptly suppressed and net hepatic glucose uptake occurred (2.8 +/- 0.2 and 2.4 +/- 0.5 mg/min X kg in group 2 and 3 respectively). Euglycemic hyperinsulinemia (group 1) suppressed postabsorptive hepatic glucose release but did not enhance glucose removal by either the liver or gut tissues. After oral glucose gut tissues released absorbed glucose into portal blood. Over three hours following the glucose meal 74% and 59% of the ingested glucose was absorbed in group 4 and 5, respectively. As with IV glucose, postabsorptive hepatic glucose production was suppressed and over the first two hours after feeding the liver took up glucose (3.4 +/- 1.0 and 3.1 +/- 0.7 mg/min X kg groups 4 and 5, respectively) at a rate similar to that seen with IV glucose. To further examine the effect of the route of glucose administration on liver glucose handling, hepatic glucose balance was measured serially over four hours in three dogs that received IV glucose into a mesenteric vein to produce portal hyperglycemia (+125 mg/dL portal glucose clamp N = 3). Oral glucose (2.5 mg/kg) was given at two hours, and the rate of the mesenteric glucose infusion adjusted to maintain portal glycemia constant. The hepatic glucose balance averaged 5.5 mg/min X kg over the 0 to 2 hour period and 4.2 +/- 1.0 mg/min X kg over the 2 to 4 hour time.(ABSTRACT TRUNCATED AT 400 WORDS)


Specific D-glucose transport in sarcolemma vesicles.
The sarcolemmal fraction prepared from rat skeletal muscle consists of osmotically active vesicles that accumulate D-glucose in preference to L-glucose, apparently by facilitated diffusion into intravesicular space. Stereospecific D-glucose uptake by these vesicles is a saturable rpocess, inhibited by phloridzin, by cytochalasin B, and by certain sugars, and enhanced by counterflow. An additional leak pathway permits entry of both D- and L-glucose into the vesicles. Stereospecific D-glucose transport by sarcolemmal vesicles is enhanced to a small extent by insulin, provided the hormone is administered prior to cell disruption. In membranes prepared from insulin-pretreated muscle, Ca2+ produces a small further enhancement. Local anesthetics preferentially inhibit stereospecific D-glucose transport. Apparent uptake of both D- and L-glucose is greater when vesicles are suspended in salt solutions rather than sucrose, an effect attributed to increased functional vesicular volume.


Phosphorylation sites are evolutionary checkpoints against liquid-solid transition in protein condensates.
Assemblies of multivalent RNA-binding protein fused in sarcoma (FUS) can exist in the functional liquid-like state as well as less dynamic and potentially toxic amyloid- and hydrogel-like states. How could then cells form liquid-like condensates while avoiding their transformation to amyloids? Here, we show how posttranslational phosphorylation can provide a "handle" that prevents liquid-solid transition of intracellular condensates containing FUS. Using residue-specific coarse-grained simulations, for 85 different mammalian FUS sequences, we show how the number of phosphorylation sites and their spatial arrangement affect intracluster dynamics preventing conversion to amyloids. All atom simulations further confirm that phosphorylation can effectively reduce the β-sheet propensity in amyloid-prone fragments of FUS. A detailed evolutionary analysis shows that mammalian FUS PLDs are enriched in amyloid-prone stretches compared to control neutrally evolved sequences, suggesting that mammalian FUS proteins evolved to self-assemble. However, in stark contrast to proteins that do not phase-separate for their function, mammalian sequences have phosphosites in close proximity to these amyloid-prone regions. These results suggest that evolution uses amyloid-prone sequences in prion-like domains to enhance phase separation of condensate proteins while enriching phosphorylation sites in close proximity to safeguard against liquid-solid transitions.


Following the Pathway of W Chromosome Differentiation in Triportheus (Teleostei: Characiformes).
In this work, we trace the dynamics of satellite DNAs (SatDNAs) accumulation and elimination along the pathway of W chromosome differentiation using the well-known Triportheus fish model. Triportheus stands out due to a conserved ZZ/ZW sex chromosome system present in all examined species. While the Z chromosome is conserved in all species, the W chromosome is invariably smaller and exhibits differences in size and morphology. The presumed ancestral W chromosome is comparable to that of T. auritus, and contains 19 different SatDNA families. Here, by examining five additional Triportheus species, we showed that the majority of these repetitive sequences were eliminated as speciation was taking place. The W chromosomes continued degeneration, while the Z chromosomes of some species began to accumulate some TauSatDNAs. Additional species-specific SatDNAs that made up the heterochromatic region of both Z and W chromosomes were most likely amplified in each species. Therefore, the W chromosomes of the various Triportheus species have undergone significant evolutionary changes in a short period of time (15-25 Myr) after their divergence.


Cribriform architecture outperforms Gleason pattern 4 percentage and tertiary Gleason pattern 5 in predicting the outcome of Grade Group 2 prostate cancer patients.
Gleason pattern 4 (GP4) percentage, invasive cribriform and/or intraductal carcinoma (IC/IDC) and the presence of tertiary Gleason pattern 5 (TP5) in radical prostatectomy (RP) specimens all aid in the risk stratification of Grade Group (GG) 2 prostate cancer patients. However, it is unclear to what extent these pathological features are mutually related and what are their individual values if they are investigated simultaneously. The aims of this study were: (i) to determine the mutual relationships of the GP4 percentage, IC/IDC and TP5 in GG2 RP specimens; and (ii) to assess their prognostic value for biochemical recurrence-free survival (BCRFS). Of 1064 RP specimens, 472 (44.4%) showed GG2 prostate cancer. Patients with ≥25% GP4 more frequently had IC/IDC (67.0% versus 43.9%; P < 0.001) and TP5 (20.6% versus 5.8%; P < 0.001) than those with <25% GP4. In unadjusted analysis, an increased GP4 percentage [hazard ratio (HR) 1.3; 95% confidence interval (CI) 1.0-1.6; P = 0.04] and IC/IDC (log rank P < 0.001) were associated with shorter BCRFS, whereas TP5 (P = 0.12) and a dichotomised (<25%, ≥25%) GP4 percentage (P = 0.10) were not. In multivariable analysis, IC/IDC was an independent prognostic factor (HR 1.9; 95% CI 1.2-2.9; P = 0.005) for BCRFS, whereas a continuous or dichotomised GP4 percentage and TP5 were not independent prognostic factors. In conclusion, a higher GP4 percentage in RP specimens was associated with more frequent IC/IDC and TP5. IC/IDC was an independent predictor for BCRFS, whereas the GP4 percentage and TP5 were not. These findings underscore the importance of routinely including the presence of IC/IDC in RP pathology reports.


Antinociceptive effects of dehydrocorydaline in mouse models of inflammatory pain involve the opioid receptor and inflammatory cytokines.
Dehydrocorydaline (DHC) is an alkaloidal component isolated from Rhizoma corydalis. Previous studies have shown that DHC has anti-inflammatory and anti-tumor effects and that it can protect the cardiovascular system. However, there are few studies of the antinociceptive effects of DHC in vivo. This study explored the antinociceptive effects and possible mechanisms of DHC in mice using two inflammatory pain models: the acetic acid-induced writhing test and the formalin paw test. The intraperitoneal administration of DHC (3.6, 6 or 10 mg/kg) showed a dose-dependent antinociceptive effect in the acetic acid-induced writhing test and significantly attenuated the formalin-induced pain responses in mice. The antinociceptive effects of DHC were not associated with changes in the locomotor activity or motor responses of animals, and no obvious acute or chronic toxic effects were observed in the mice. Furthermore, the use of naloxone confirmed the involvement of the opioid receptor in the central antinociceptive effects of DHC. DHC reduced formalin-induced paw edema, which indicated that DHC may produce an anti-inflammatory effect in the periphery. In the formalin test, DHC decreased the expression of caspase 6 (CASP6), TNF-α, IL-1β and IL-6 proteins in the spinal cord. These findings confirm that DHC has antinociceptive effects in mice.


Estrogen suppression in premenopausal women following 8 weeks of treatment with exemestane and triptorelin versus triptorelin alone.
Luteinizing hormone-releasing hormone (LHRH) agonists (e.g., triptorelin) reduce ovarian estrogen production in premenopausal women with hormone-sensitive breast cancer. Aromatase inhibitors (e.g., exemestane) inhibit extraovarian production of estrogen and may further reduce circulating estrogens when combined with an LHRH agonist. Healthy premenopausal women were randomized to receive 3.75 mg triptorelin (T) on days 1 and 29 with 25 mg exemestane (EX) or matched placebo once daily for 8 weeks, from day 1 to day 56. The primary objective was to evaluate the effect of T +/- EX on estradiol (E(2)) suppression by comparing the AUC(day 36-57 )for the 2 treatments. Secondary objectives included evaluation of estrone (E(1)), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) suppression; effects of EX on the T-induced gonadotrophin and estrogen flare; pharmacokinetics (PK); and safety. Twenty-eight (14 in each arm) were evaluable for efficacy and PK. Mean plasma estrogen levels (AUC(day 36-57)) were significantly lower for subjects who received T + EX than for subjects who received T alone (20.6 vs. 54.0 pg d/ml [-62%; P < 0.05], and 38.9 vs. 198.0 pg d/ml [-80%; P < 0.01] for E(2) and E(1), respectively). Coadministration of EX did not affect the initial flare or subsequent suppression of LH and FSH following the first dose of T, or the PK of T. Both treatments were well tolerated. Coadministration of T and EX resulted in greater estrogen suppression than when T was given alone. These findings could translate into improved clinical outcomes for premenopausal breast cancer patients receiving LHRH agonists.


A simple high performance liquid chromatographic method for the quantification of total cotinine, total 3'-hydroxycotinine and caffeine in the plasma of smokers.
A simple isocratic HPLC procedure has been developed for the quantification of caffeine and the nicotine metabolites cotinine, 3'-hydroxycotinine, cotinine glucuronide and 3'-hydroxycotinine glucuronide in the plasma of smokers. The glucuronide conjugates were determined indirectly via initial basic hydrolysis of the analyte sample followed by quantification of the resulting deconjugation product. Plasma was basified, extracted with dichloromethane, evaporated, the residue dissolved water and an aliquot part was analyzed by HPLC. The method utilized a Partisil-10 SCX cation-exchange column and an isocratic mobile phase of sodium phosphate buffer: methanol (92:8 v/v, 0.1 M, adjusted to pH 4.8 with triethylamine) at a flow rate of 1.5 ml/min. UV detection was at 254 nm. All solutes were separated with good resolution, and quantification was determined using an internal standard of N,N-diethylnicotinamide. The retention times were: caffeine 5.1 min, 3'-hydroxycotinine 7.2 min, N,N-diethylnicotinamide 9.5 min, and cotinine 15.5 min. Detection limits for caffeine, 3'-hydroxycotinine, cotinine, and total cotinine were 10 ng/ml; the detection limit for total 3'-hydroxycotinine was 20 ng/ml. The inter-day and intra-day variations for all analytes were between 1 and 8%. This analytical method is suitable for the determination of caffeine and nicotine metabolite levels in large numbers of clinical samples.


[Double blind study of the efficacy and safety of the fixed dose combination of enalapril 10 mg/nitrendipine 20 mg versus the increase of amlopidine dose in essential hypertensive patients not controlled with amlodipine 5 mg].
Combined therapy or dose-tiration are acceptable second-line therapeutic options after a first treatment failure. This double blind clinical trial compared the fixed dose combination of enalapril 10 mg/nitrendipine 20 mg (E/N) with amlopidine 10 mg (A) in 323 hypertensive patients not previously controlled with amlodipine 5 mg. After 6 weeks of treatment, the E/N and A groups had similar percentages of blood pressure normalization (55% versus 60.2%; p = 0.4588). The adverse events related with the treatment were significantly less frequent with E/N than with a (19.8% versus 37%; p = 0.0029), especially due to a lower incidence of malleolar edema in E/N (11.1% versus 33.6%; p < 0.0001). Combining the efficacy and tolerability data, treatment with E/N permitted control of blood pressure of 2.8 patients per every patient with adverse events, while this rate for A was 1.6 to 1.


Effects of effluent organic matter (EfOM) on the removal of emerging contaminants by ozonation.
Removal of emerging contaminants in wastewater treatment is essential to ensure the ecological health of the receiving water bodies. Ozonation is a promising technology to achieve this purpose but important wastewater characteristics affecting the optimal removal efficiency need to be elucidated. Secondary effluents contain effluent organic matter (EfOM), which can react directly with ozone as well as react as the initiator, promoter and inhibitor in the hydroxyl radical (.OH) chain reactions resulting from ozone decomposition. These different reaction modes of EfOM, coupled with alkalinity and pH value, collectively determine the ozone and .OH exposures and the degradation of pharmaceutical compounds by ozonation. In this study, we determined the rate constants of EfOM collected from two municipal wastewater treatment plants in terms of direct ozone reaction, initiation, promotion and inhibition at various pH values (pH 6.0-7.5) and temperatures (10-30 °C). The rate constants of direct reaction and initiation generally increased with the increasing pH value while the rate constants of promotion and inhibition did not vary significantly. All rate constants increased with the increasing temperature. The removal of ibuprofen, acetylsulfamethoxazole and metoprolol in diluted secondary effluent by ozonation can be fairly-well modeled by using the determined rate constants of EfOM.


Intragenic proviral elements support transcription of defective HIV-1 proviruses.
HIV-1 establishes a persistent proviral reservoir by integrating into the genome of infected host cells. Current antiretroviral treatments do not target this persistent population of proviruses which include latently infected cells that upon treatment interruption can be reactivated to contribute to HIV-1 rebound. Deep sequencing of persistent HIV proviruses has revealed that greater than 90% of integrated HIV genomes are defective and unable to produce infectious virions. We hypothesized that intragenic elements in the HIV genome support transcription of aberrant HIV-1 RNAs from defective proviruses that lack long terminal repeats (LTRs). Using an intact provirus detection assay, we observed that resting CD4+ T cells and monocyte-derived macrophages (MDMs) are biased towards generating defective HIV-1 proviruses. Multiplex reverse transcription droplet digital PCR identified env and nef transcripts which lacked 5' untranslated regions (UTR) in acutely infected CD4+ T cells and MDMs indicating transcripts are generated that do not utilize the promoter within the LTR. 5'UTR-deficient env transcripts were also identified in a cohort of people living with HIV (PLWH) on ART, suggesting that these aberrant RNAs are produced in vivo. Using 5' rapid amplification of cDNA ends (RACE), we mapped the start site of these transcripts within the Env gene. This region bound several cellular transcription factors and functioned as a transcriptional regulatory element that could support transcription and translation of downstream HIV-1 RNAs. These studies provide mechanistic insights into how defective HIV-1 proviruses are persistently expressed to potentially drive inflammation in PLWH.


Pathologic features associated with nonsentinel lymph node metastases in patients with metastatic breast carcinoma in a sentinel lymph node.
To the authors' knowledge it has not yet been determined which patients with primary breast carcinoma and an axillary sentinel lymph node (SN) metastasis have additional metastases in nonsentinel lymph nodes. Pathologic features of the primary breast carcinoma and its SN metastasis were examined in 194 patients and correlated with the tumor status of the non-SNs in the same axillary basin. Two-level cytokeratin immunohistochemistry was applied to the SNs and to non-SNs of cases that were negative by standard hematoxylin and eosin examination. Lymph node staging based on SN findings, size of the primary tumor, and presence of peritumoral lymphatic vascular invasion (LVI) were associated with non-SN metastasis. The majority (63%) of the 101 patients with SN macrometastases had non-SN metastases. Extranodal hilar tissue invasion in conjunction with SN involvement also was strongly associated with non-SN metastasis (P = 0.0001) but was present in only 65% of patients (35 of 54 patients) with non-SN macrometastases. Approximately 26% of patients (24 of 93 patients) with SN micrometastases (</= 2.0 mm) had non-SN metastases; among these patients only primary tumor size and peritumoral LVI were correlated with non-SN metastasis. Detailed pathologic examination of the primary tumor and its SN metastasis may increase precision in the selection of patients for further axillary surgery or radiation therapy.


Prospective hematologic and clinicopathologic study of asymptomatic cats with naturally acquired feline immunodeficiency virus infection.
Prospective studies were performed over a 28- to 77-month period (median, 66 months) on 5 cats with naturally acquired feline immunodeficiency virus (FIV) infection in an attempt to correlate hematologic and clinicopathologic changes with the emergence of clinical disease. On presentation, all cats were asymptomatic; free of opportunistic infections; and had normal complete blood counts, bone marrow morphologies, marrow progenitor frequencies, and progenitor in vitro growth characteristics. During study, 2 cats remained healthy, 2 cats showed mild clinical signs, and 1 cat developed a malignant neoplasm (ie, bronchiolar-alveolar adenocarcinoma). Although persistent hematologic abnormalities were not observed, intermittent peripheral leukopenias were common. In 3 of 5 FIV-seropositive cats, lymphopenia (< 1,500 lymphs/microL; normal reference range, 1,500 to 7,000 lymphs/microL) was a frequent finding and the absolute lymphocyte counts had a tendency to progressively decline. One of the other 2 cats had consistently low to low-normal absolute neutrophil counts (1,300 to 4,800 segs/microL; mean, 2,730 segs/microL; normal reference range, 2,500 to 12,500 segs/microL), and the remaining cat had consistently normal leukograms, except for a transient period (ie, 11 months) of benign lymphocytosis (7,200 to 13,430 lymphs/microL) early in the study. Periodic examinations of bone marrow aspirates revealed normal to slightly depressed myeloid-to-erythroid ratios with normal cellular morphology and maturation. Bone marrow abnormalities observed late in the study included mild dysmorphic changes (ie, megaloblastic features) in 2 cats, and a significant decrease (60% of controls, P < .001) in the frequencies of burst-forming units erythroid (BFU-E) in marrow cultures of FIV-seropositive cats compared with uninfected control cats.(ABSTRACT TRUNCATED AT 250 WORDS)


A comparison of methane emissions following rice paddies conversion to crab-fish farming wetlands in southeast China.
Rice paddies and aquaculture wetlands are typical agricultural wetlands that constitute one of the important sources of atmospheric methane (CH4). Traditional transplanted rice paddies have been experiencing conversion to pond aquaculture wetlands for pursuing higher economic benefits over the past decades in southeast China. A parallel field experiment was carried out to compare CH4 emissions from a transplanted rice paddy and its converted crab-fish farming wetland in southeast China. Over the rice-growing season, CH4 fluxes averaged 1.86 mg m(-2) h(-1) from rice paddies, and 1.14 and 0.50 mg m(-2) h(-1) for the treatments with or without aquatic vegetation present in the crab-fish farming wetlands, respectively. When averaged across the treatments, seasonal CH4 emissions from crab-fish framing wetlands were 52% lower than those from rice paddies. The CH4 fluxes were negatively related to water dissolved oxygen (DO) concentration but positively related to soil/sediment dissolved organic carbon (DOC) content in crab-fish farming wetlands. Dependence of CH4 fluxes on DO or DOC was intensified by the aquatic vegetation presence. By extrapolating the present CH4 emission rate with the current rice paddy-converted aquaculture cultivation area, the seasonal CH4 emissions from inland aquaculture wetlands during the critical farming stage (20 June to 18 October) were estimated to be 33.6 Gg ha(-1) in southeast China in 2012. Rice paddies conversion to crab-fish farming wetlands might have reduced CH4 emissions by 22-54% in mainland China. Results of this study suggest that the conversion of transplanted rice paddies to crab-fish aquaculture wetlands for higher economic benefits would also lead to a lower ecosystem CH4 release rate.


Comparison of the nucleotide and amino acid sequences of the RsrI and EcoRI restriction endonucleases.
The RsrI endonuclease, a type-II restriction endonuclease (ENase) found in Rhodobacter sphaeroides, is an isoschizomer of the EcoRI ENase. A clone containing an 11-kb BamHI fragment was isolated from an R. sphaeroides genomic DNA library by hybridization with synthetic oligodeoxyribonucleotide probes based on the N-terminal amino acid (aa) sequence of RsrI. Extracts of E. coli containing a subclone of the 11-kb fragment display RsrI activity. Nucleotide sequence analysis reveals an 831-bp open reading frame encoding a polypeptide of 277 aa. A 50% identity exists within a 266-aa overlap between the deduced aa sequences of RsrI and EcoRI. Regions of 75-100% aa sequence identity correspond to key structural and functional regions of EcoRI. The type-II ENases have many common properties, and a common origin might have been expected. Nevertheless, this is the first demonstration of aa sequence similarity between ENases produced by different organisms.


Impaired tuftsin activity in cirrhosis: relationship with splenic function and clinical outcome.
Cirrhotic patients show increased susceptibility to bacterial infections. It is not known whether tuftsin deficiency, which is associated with an increased incidence of infections in many disease states, is present in cirrhosis. Our aims were to determine whether tuftsin activity is deficient in cirrhosis and if so, whether this deficiency is related to splenic function, contributes to altered neutrophil granulocyte function, or influences the occurrence of bacterial infections and patient survival. Tuftsin activity and splenic function were assessed in 31 patients with liver cirrhosis and 31 healthy subjects. The phagocytic activity of neutrophil granulocytes from 23 patients was tested in vitro with addition of both autologous and pooled sera from healthy subjects. In 10 patients and eight controls it was also tested with addition of synthetic tuftsin. Patients were followed up until death or liver transplantation. Patients had reduced tuftsin activity (median 8% (range 3-24.5)) compared with controls (17% (11.5-37)) (p<0.001) and a higher pitted red cell count (p<0.001). Tuftsin activity was correlated with pitted cell count (p=0.02) and the Child-Pugh score (p=0.002). Nineteen of 23 patients showed deficient phagocytic activity of neutrophil granulocytes, which was correlated with tuftsin activity (p<0.001), improved in all cases but one with addition of serum from healthy subjects, and normalised with addition of synthetic tuftsin. Reduced tuftsin activity did not influence patient survival but was associated with a higher incidence of bacterial infections (p=0.029). Tuftsin activity was reduced in cirrhosis, and contributed to impaired phagocytic activity of neutrophil granulocytes. Such an abnormality appears to be related to impaired splenic function and severity of cirrhosis, and probably favours the occurrence of bacterial infections.


Studies on mast cells of Rana tigrina.
Mast cell degranulators cause vasoconstriction in the frog. A comparative study of the mesenteric mast cells of the frog and rat showed that the frog mast cells differed from those of the rat in having a dense perigastric instead of a sparse ideal distribution, and in responding to compound 48/80 by a rapid and marked disappearance and/or fragmented appearance instead of classical degranulation. The vasoconstriction and mast cell response after in vivo compound 48/80 appeared related since they showed a parallel increase when the dose was increased.


Micro-fractional, directional skin tightening: A porcine model.
Skin changes are among the most visible signs of aging. Fractional ablative lasers improve skin quality by making small skin wounds that heal rapidly without scarring. While they improve skin texture and discoloration, there is minimal effect on skin laxity. This study was performed to assess skin shrinkage performed by removing multiple small full-thickness skin columns with coring needles combined with wound closure. In 5 swine 116 squares (3 cm(2) ) were demarcated for treatment and control sites. In treatment sites 10% of the skin was removed by full-thickness skin coring needles (19 gauge) and afterwards closed and compressed with an elastic adhesive dressing. This procedure was compared to puncturing the skin with standard hypodermic needles (without tissue removal) and subsequent closure with compressive dressing. Area and shape of sites were measured before and 28 days after treatment. Test and control sites healed within a week without scarring. Coring with wound closure caused significant shrinkage after 28 days. The treated skin area was reduced by 9% (P < 0.0001) and the direction of shrinkage was influenced by the direction of wound closure. Coring without wound closure and puncturing the skin without tissue removal produced an insignificant 3% decrease in area. Significant minimally invasive skin tightening in a preferred direction can be achieved by removing skin with coring needles followed by wound closure. The direction of shrinkage is influenced by the direction of micro-hole closure, irrespective of the skin tension lines. This approach may allow reshaping the skin in a desired direction without scarring.


Complete annotated genome sequence of Mycobacterium tuberculosis Erdman.
We report the completely annotated genome sequence of Mycobacterium tuberculosis Erdman (TMC 107; ATCC 35801), which is a well-known laboratory strain of M. tuberculosis.


Treatment of Wide-Necked Cerebral Aneurysms Using the WEB Device Including Flow Alteration Assessment With Color-Coded Imaging: A Single Center Experience.
The Woven EndoBridge (WEB) device (MicroVention, Tustin, CA) has extended the treatment of cerebral aneurysms. Despite the fact that the WEB device has shown promising clinical results, little is known about the caused intra-aneurysmal flow alterations. Here we present our clinical experience with the WEB, including examining various syngo iFlow (Siemens AG, Erlangen, Germany) parameters to predict aneurysm occlusion. We reviewed the data from patients with unruptured cerebral aneurysms treated with a WEB device between 2016 and 2020. Aneurysm occlusion and complications were assessed. Furthermore, different quantitative criteria were evaluated using syngo iFlow after digital subtraction angiography. A total of 26 patients hosting 26 cerebral aneurysms met the inclusion criteria. Follow-up was available for 21 patients, with a mean of 7.3 ± 6.3 months. A total of 71.4% (n = 15) of the aneurysms included were located in the anterior and 28.6% (n = 6) in the posterior circulation. Adequate aneurysm occlusion was achieved in 85.7% (n = 18). The iFlow parameters for reduced aneurysm outflow (ID-R) differed significantly from the parameters for reduced inflow (PI-R and PI-D) (P < 0.001). The parameters did not differ significantly between adequately and insufficiently occluded aneurysms. Only a trend towards a lower ID-R of insufficiently occluded aneurysms was observed (P = 0.063), indicating a potential predictive value for insufficient aneurysmal outflow. There was no treatment-related morbidity or mortality. The applied syngo iFlow parameters confirmed that flow changes induced by the WEB device significantly affect outflow compared to inflow and have potential predictive value for adequate aneurysm occlusion.


[Eco-physiological studies on desert plants : V. Influence of soaking and redrying on the germination of Zygophyllum coccineum seeds and the possible contribution of an inhibitor to the effect].
1. The rate and percentage of germination of soaked and redried seeds are higher than those of untreated seeds. The promoting effect of soaking and redryring of seeds on germination increases with the duration of soaking. Seeds that germinated during soaking are unable to tolerate drying. 2. Exposure of the seeds to light after the first 8 hours of soaking inhibits germination of the seeds after drying. 3. Washing the seeds with water has no effect on germination in the dark at 25°C, while it promotes germination in light at 25°C and in the dark at 10°C. 4. The leachate of Zygophyllum coccineum seeds has no significant effect on the dark germination of these seeds. On the other hand, it inhibits the light germination. Germination of Lepidium sativum seeds is not affected by the leachate of Zygophyllum seeds, either in the dark or in light. 5. When the washed seeds of Zygophyllum coccineum are germinated, their radicles are longer and the hypocotyls shorter than in the controls. The leachate promotes hypocotyl growth and inhibits that of the radicle. 6. A hypothesis is suggested to interpret the results based on the assumed interaction between seeds, light and an inhibitor.


The abundant world: Paul Feyerabend's metaphysics of science.
The goal of this paper is to provide an interpretation of Feyerabend's metaphysics of science as found in late works like Conquest of Abundance and Tyranny of Science. Feyerabend's late metaphysics consists of an attempt to criticize and provide a systematic alternative to traditional scientific realism, a package of views he sometimes referred to as "scientific materialism." Scientific materialism is objectionable not only on metaphysical grounds, nor because it provides a poor ground for understanding science, but because it implies problematic claims about the epistemic and cultural authority of science, claims incompatible with situating science properly in democratic societies. I show how Feyerabend's metaphysical view, which I call "the abundant world" or "abundant realism," constitute a sophisticated and challenging form of ontological pluralism that makes interesting connections with contemporary philosophy of science and issues of the political and policy role of science in a democratic society.


Sulbactam improves binding property and uptake capacity of glutamate transporter-1 and decreases glutamate concentration in the CA1 region of hippocampus of global brain ischemic rats.
Glutamate transporter-1 (GLT-1) removes most glutamate in the synaptic cleft. Sulbactam confers neuronal protection against ischemic insults in the hippocampal CA1 region accompanied by the upregulation of GLT-1 expression in rats. The present study further investigates the effect of sulbactam on the binding property and uptake capacity of GLT-1 for glutamate, and the change in extracellular glutamate concentration in the hippocampal CA1 region of rats with global brain ischemia. The binding property and uptake capacity of GLT-1 were measured using a radioligand binding and uptake assay, respectively, with L-3H-glutamate. The extracellular glutamate concentration was detected using microdialysis and high-performance liquid chromatography-mass spectrometry. Neuropathological evaluation was performed based on thionin staining. It was shown that sulbactam pre-treatment changed GLT-1 binding property, including increased Bmax and decreased Kd values, increased GLT-1 uptake capacity for glutamate, and inhibited the elevation of extracellular glutamate concentration in rats with global cerebral ischemia. These effects of sulbactam were accompanied by its neuronal protection on the hippocampal CA1 neurons against delayed neuronal death resulted from ischemic insult. Furthermore, administration of GLT-1 antisense oligodeoxynucleotides, which inhibited the expression of GLT-1, blocked the aforementioned sulbactam-related effects, which suggested that GLT-1 upregulation mediated the above effect although other mechanisms independent of the upregulation of GLT-1 expression could not be excluded. It could be concluded that sulbactam improves the binding property and uptake capacity of GLT-1 for glutamate and then reduces the glutamate concentration and excitotoxicity during global cerebral ischemia, which contributes to the neuroprotection of sulbactam against brain ischemia.


¹⁸F-labeled 2-phenylquinoxaline derivatives as potential positron emission tomography probes for in vivo imaging of β-amyloid plaques.
In continuation of our study on the 2-phenylquinoxaline scaffold as potential β-amyloid imaging probes, two [(18)F]fluoro-pegylated 2-phenylquinoxaline derivatives, 2-(4-(2-[(18)F]fluoroethoxy)phenyl)-N-methylquinoxalin-6-amine ([(18)F]4a) and 2-(4-(2-(2-(2-[(18)F]fluoroethoxy)ethoxy)ethoxy)phenyl)-N-methylquinoxalin-6-amine ([(18)F]4b) were prepared. Both of them displayed high binding affinity to Aβ(1-42) aggregates (K(i) = 10.0 ± 1.4 nM for 4a, K(i) = 5.3 ± 3.2 nM for 4b). The specific and high binding of [(18)F]4a and [(18)F]4b to Aβ plaques was confirmed by in vitro autoradiography on brain sections of AD human and transgenic mice. In biodistribution in normal mice, [(18)F]4a displayed high initial brain uptake (8.17% ID/g at 2 min) and rapid washout from the brain. These preliminary results suggest [(18)F]4a may be a potential PET imaging agent for Aβ plaques in the living human brain.


Oral contraceptive use induces upregulation of the CCR5 chemokine receptor on CD4(+) T cells in the cervical epithelium of healthy women.
Heterosexual transmission of human immunodeficiency virus type I (HIV-1) is the predominant mode of infection worldwide. Increased risk of HIV-1 transmission has been reported with oral contraceptive use. To elucidate the underlying mechanism of this observation, intraepithelial endocervical T lymphocytes from women using oral contraceptives were analysed for expression of activation and chemokine receptors. T lymphocytes from the cervical epithelium and peripheral blood of women using combined oral contraceptives (COC) and those using no contraceptive method (NONE) were compared. Cervical T lymphocytes were obtained with a cytobrush and in parallel, mononuclear leukocytes were separated from blood by centrifugation over a ficoll-hypaque gradient. Cellular activation markers and HIV-1 chemokine co-receptors, CXCR4 and CCR5, were analysed by flow cytometry. Activation markers (CD69, CD25 and HLA-DR) on T cells were expressed at higher levels in the cervical epithelium than peripheral blood T cells but were no different in those women using COC. CXCR4 was widely expressed on cervical and on blood T cells, but was not influenced by COC use. By contrast, the number of T cells expressing CCR5 increased in women using COC (P<0.05). The level of cervical CCR5 expression per cell was shown to increase on both activated CD4(+) (CD69(+), P<0.05; HLA-DR(+), P<0.01) and CD8(+) (CD69(+), P<0.05; HLA-DR(+), P<0.05) T lymphocytes compared with COC use. These data show that with COC use, the expression of CCR5 on CD4(+) T lymphocytes is increased. Furthermore, the cell surface density of CCR5 is increased on both CD4(+) and CD8(+) T lymphocyte subsets. These findings suggest a mechanism by which oral contraceptive use can increase the risk of HIV-1 transmission.


Recruitment and Retention of South Asian Ethnic Minority Populations in Behavioral Interventions to Improve Type 2 Diabetes Outcomes.
South Asian (SA) immigrants have a higher burden of type 2 diabetes, report poor self-management, and remain a hard-to-engage group in behavioral interventions. The purpose of this review was to characterize recruitment and retention of SAs in behavioral interventions. We identified 14 studies with limited information regarding recruitment and retention. Overall recruitment rates were low: 12 studies had a mean recruitment rate of 44% among those screened, and 9 studies with complete information on eligibility had a mean recruitment rate of 65.8% among those eligible. Mean retention rate was 79.4% across all 14 studies. Although unstandardized and inconsistent reporting limited our ability to draw any conclusions regarding the best strategies to maximize recruitment and retention, we were able to highlight some novel and effective strategies. There is a need for consistent and standardized reporting of recruitment and retention-related information to encourage meaningful research and guide researchers in efficient allocation of resources and a successful conclusion of future interventions.


The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Recommendation Using the Delphi Method (Version 2023.1).
During the coronavirus disease 2019 (COVID-19) pandemic, the need for appropriate treatment guidelines for patients with brain tumors was indispensable due to the lack and limitations of medical resources. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. The KSNO Guideline Working Group was composed of 22 multidisciplinary experts on neuro-oncology in Korea. In order to reach consensus among the experts, the Delphi method was used to build up the final recommendations. All participating experts completed the series of surveys, and the results of final survey were used to draft the current consensus recommendations. Priority levels of surgery and radiotherapy during crises were proposed using appropriate time window-based criteria for management outcome. The highest priority for surgery is assigned to patients who are life-threatening or have a risk of significant impact on a patient's prognosis unless immediate intervention is given within 24-48 hours. As for the radiotherapy, patients who are at risk of compromising their overall survival or neurological status within 4-6 weeks are assigned to the highest priority. Curative-intent chemotherapy has the highest priority, followed by neoadjuvant/adjuvant and palliative chemotherapy during a crisis period. Telemedicine should be actively considered as a management tool for brain tumor patients during the mass infection crises such as the COVID-19 pandemic. It is crucial that adequate medical care for patients with brain tumors is maintained and provided, even during times of crisis. This guideline will serve as a valuable resource, assisting in the delivery of treatment to brain tumor patients in the event of any future crisis.


Fathers' functional status during pregnancy and the early postnatal period.
to determine the functional status of fathers whose wives were pregnant or in the early postnatal period. the research population comprised 3750 fathers whose wives were pregnant or in the early postnatal period, and who were registered at a primary health clinic in the province centre. The research sample comprised 275 husbands of women who were registered at these clinics and who were in at least their 28th week of a normal (not at-risk) pregnancy with a single fetus, or who were in the early postnatal period (6-8 weeks postnatal) following birth of a single baby between the 38th and 42nd week without complications. Due to fathers declining to participate in the study or unable to participate because of busy work schedules, the research was completed with 155 fathers-to-be and 93 fathers; in total, 90% of the target sample was reached. A sociodemographic survey and the Inventory of Functional Status-Fathers were used for data collection and to describe the functional abilities of fathers-to-be and fathers. no statistically significant differences were found in functional status between the husbands of pregnant women and the husbands of women in the early postnatal period. Number of pregnancies was not significantly related to any of the seven subscales of fathers' functional status; age of husband, length of marriage and occupation of wife were significantly related to one subscale; occupation of husband and health insurance were significantly related to two subscales; income status of husband and educational level of wife were significantly related to three subscales; and educational level of husband was significantly related to four subscales. although there was no significant difference in functional status for the husbands of pregnant women and the husbands of postnatal women, sociodemographic factors were found to have an effect.


Studies on the 14.5 nm meridional X-ray diffraction reflection during length changes of intact frog muscle fibres.
The intensity of the 14.5 nm meridional reflection (M3) from activated skeletal muscle fibres was studied in both single fibres and fibre bundles during the imposition of length changes. During shortening at small load, the intensity of the reflection decreased within 2 ms to less than 20% of isometric intensity, then recovered partially during the remainder of the shortening. When shortening was terminated, recovery of intensity was delayed. Small shortening steps (0.5% fibre length) produced a fall in M3 intensity (IM3) delayed by ca. 250 microseconds compared to the fall in tension. For larger step releases (1% fibre length), the fall in IM3 was not delayed. The fall in IM3 could be almost completely reversed by a subsequent restretch applied within 1.5 ms. Beyond 10 ms after the initial release, the restretch caused a further fall in intensity. A rapid step stretch (0.5% fibre length) also caused a fall in IM3 without delay, which was partially reversed by a release applied within 10 ms. A second small release applied 3 ms (or less) after the first caused a second fall in M3 intensity, but without delay and with faster time course. Small amplitude sinusoidal length oscillations (0.15-0.2% sarcomere; 1 kHz) caused a sinusoidal change in M3 intensity, which was 180 degrees out of phase with the force oscillations, and lacked distortion during its release phase.


Obstructive site localization using multisensor manometry versus the Friedman staging system in obstructive sleep apnea.
The aim of this study was to find the correlation between an anatomy-based staging system and pressure manometry performed during sleep. A retrospective study of 45 patients with obstructive sleep apnea (OSA) was carried out. All patients were evaluated by polysomnography, and obstruction sites were localized using a multisensor manometer during the full night. Obstruction sites were classified into retropalatal and retroglossal. The patients were also staged by anatomic findings of tonsil size and palate position. The % retroglossal obstruction was 29.4, 33.5 and 48.6% in stages I, II and III, respectively. There was no significant difference between stages. In contrast, when compared according to the Friedman tongue position (FTP), the mean % retroglossal obstruction of FTP grade 3 was significantly higher than that of FTP grade 1 (P = 0.009) although apnea hypopnea index, body mass index and lowest SpO2 were not different among FTP grades. It seems that FTP correlates with retroglossal obstruction and may be used to select patients in need of retroglossal modification of the airway.


Alteration of lumbar muscle morphology and composition in relation to low back pain: a systematic review and meta-analysis.
Previous studies have proposed that there is a relationship between low back pain (LBP) and morphology and composition of paraspinal muscles. However, results have been conflicting, especially regarding fatty infiltration of muscles. The primary goal of this study was to review and analyze results from imaging studies which investigated morphological and composition changes in the multifidus, erector spinae and psoas major muscles in people with LBP. Systematic review with meta-analysis. A patient sample was not required OUTCOME MEASURES: This review did not have outcome measures. PubMed, Scopus, Web of Sciences, EMBASE and ProQuest were searched for eligible studies up to 31st July 2020 (all languages). A systematic search of electronic databases was conducted to identify studies investigating the association between the morphology and fat content of lumbar muscles in people with LBP compared with a (no LBP) control group. 13,795 articles were identified. Based on the screening for inclusion/ exclusion, 25 were included. The quality of the studies was evaluated using the Newcastle-Ottawa Scale. From the 25 articles, 20 were included in the meta-analysis. Results showed that the total cross-sectional area of the multifidus was smaller in people with LBP (Standardized mean difference, SMD = -0.24, 95% CI = -0.5 to 0.03). Combined SMDs showed a medium effect of LBP on increasing multifidus muscle fat infiltration (SMD = 0.61, 95% CI = 0.30 to 0.91). There were no LBP related differences identified in the morphology or composition of the lumbar erector spine and psoas major muscles. People with LBP were found to have somewhat smaller multifidus muscles with a significant amount of intramuscular fat infiltration. Varying sample size, age and BMI of participants, quality of studies and the procedures used to measure fat infiltration are possible reasons for inconsistencies in results of previous studies.


Biochemical mediators of the effects of mechanical forces and electric currents on mineralized tissues.
Cyclic nucleotides (cAMP and cGMP) and prostaglandin E (PGE) have been implicated as possible mediators of the effects of external stimuli on bone cells. The objective of this study was to determine changes in relative levels of these substances in mineralized tissue cells in response to mechanical and electrical stimuli, by the use of a combined immunohistochemical-microphotometric procedure. Canine teeth of eight 10-12 month-old female cats were tipped distally with 80 g force for either 1 h or 14 days. After 1 h, a slight elevation of staining intensity in alveolar bone osteoblasts and periodontal ligament (PDL) cells was observed at sites of tension and compression. After 14 days of treatment, this effect was markedly increased. Fifteen female cats, 10-12 months old, received electric stimulation (20 micron amperes d.c.) to the gingiva of 1 maxillary canine for 1, 5, 15, 30, or 60 min. At the cathode, significant increases of staining intensity in periosteal osteoblasts for cAMP, cGMP, and PGE were found at 15 and 60 min. At the anode, a significant rise in the staining intensity of these cells for PGE was seen at 15 min; at 60 min, cGMP and PGE, but not cAMP, were elevated. These results demonstrate the usefulness of the immunohistochemical technique in detecting relative changes in mineralized tissue cell content of cyclic nucleotides and prostaglandins in response to local application of physical stimuli of short and long duration.


Potential impact of improvements in radiation therapy on quality of life and survival.
The NCI goal for the U.S. is to reduce the cancer mortality rate to one-half by the year 2000. Part of this improvement will be due to use of state of art treatment on a population wide basis and in addition, major improvements in efficacy of treatment. More effective radiation therapy will result in fewer local failures, increased survival, reduced treatment associated morbidity, and less frequent complications of treatment. The latter two aspects are very important to quality of life. If radiation combined with other modalities (e.g., sensitizers) were to become of greatly enhanced efficacy, then the number of patients requiring cystectomy, abdominal perineal resection, pneumonectomy, amputation, etc., would come down. The beneficial consequence would be fewer patients subjected to permanent ileostomy, colostomy, etc. The increase in survival if local failure were eliminated was estimated to be the decrease in local failure less the same loss in the new local controls due to DM as obtained in the local control patients after conventional treatment. For all sites, patients experience higher survival rates if they do not have local failure. For those sites where loss due to metastasis is not high, more effective local therapy would result in numerically impressive gains in survival.


YWHAZ and TBP are potential reference gene candidates for qPCR analysis of response to radiation therapy in colorectal cancer.
The expression profiles of conventional reference genes (RGs), including ACTB and GAPDH, used in quantitative real-time PCR (qPCR), vary depending on tissue types and environmental conditions. We searched for suitable RGs for qPCR to determine the response to radiotherapy in colorectal cancer (CRC) cell lines, organoids, and patient-derived tissues. Ten CRC cell lines (Caco-2, COLO 205, DLD-1, HCT116, HCT-15, HT-29, RKO, SW1116, SW480, and SW620) and organoids were selected and irradiated with 2, 10 or 21 grays (Gy) based on the previous related studies conducted over the last decade. The expression stability of 14 housekeeping genes (HKGs; ACTB, B2M, G6PD, GAPDH, GUSB, HMBS, HPRT1, IPO8, PGK1, PPIA, TBP, TFRC, UBC, and YWHAZ) after irradiation was evaluated using RefFinder using raw quantification cycle (Cq) values obtained from samples before and after irradiation. The expression stability of HKGs were also evaluated for paired fresh frozen tissues or formalin-fixed, paraffin-embedded samples obtained from CRC patients before and after chemoradiotherapy. The expression of YWHAZ and TBP encoding 14-3-3-zeta protein and TATA-binding protein were more stable than the other 12 HKGs in CRC cell lines, organoids, and patient-derived tissues after irradiation. The findings suggest that YWHAZ and TBP are potential RG candidates for normalizing qPCR results in CRC radiotherapy experiments.


[Fractures of the neck of femur in juveniles (author's transl)].
The problems of the treatment of femoral neck fractures in young patients are discussed on 22 cases as well as the operative technique, post-operative treatment, late complications and their treatment. We feel that femoral neck fractures in children and young ones should be treated operatively. The three flanged nail should be used for internal fixation, giving a better fixation than K-wires. We have not seen any damage caused by the crossing of the epiphyseal plate with a nail or K-wires. Postoperatively the patient should walk non weight bearing on the fractured hip for 9 months, especially in transcervical fractures. The danger of aseptic necrosis of the femoral head is clearly diminished by this precaution. The late results of femoral neck fractures in juveniles are clearly worse than in children. The femoral neck fracture of the young is to be treated as an emergency. If the therapy is too late or not adequate the consequences for the hip joints of the juveniles can be drastic.


Media for Salmonella.
The main categories of selective plating media are reviewed. The selective enrichment media are considered to be of critical importance in salmonella isolation. During the last 10 years Rappaport-Vassiliadis broth has emerged as a new reliable enrichment medium. Likewise motility enrichment is a very promising technique, but will no doubt have its limitations. However, since it is based on a different principle compared with traditional enrichment, it may complement traditional techniques in a useful way. Most important, however, is the insight that the selectivity of a selective procedure is not solely defined by the medium and by incubation conditions. The food sample and its microflora apparently influences the result considerably. This finding may open a new and fascinating field of scientific research; the ecology of selective media.


A history of cryptorchidism: lessons from the eighteenth century.
John Hunter in 1786 opened the door to more than 200 years of study and discussion of the cryptorchid testis. We review the history that has brought us to our current surgical treatment of this condition. We performed a review of the medical and historical surgical literature pertaining to cryptorchidism. The study of cryptorchidism began with the anatomical descriptions of Baron Albrecht von Haller and John Hunter. Attempts at surgical correction of the undescended testis began in the early 1800s, culminating in the first successful orchidopexy by Thomas Annandale in 1877. Further contributions to the surgical technique include: (1) Arthur Dean Bevan's division of the processus vaginalis to prevent reascent and his stress on the importance of adequate mobilization of the spermatic cord, (2) the description by Robert Prentiss of surgical triangles which allowed for mobilization of the spermatic cord and placement of the testis into the scrotum without tension, and (3) Lattimer's subdartos pouch. Our understanding and the surgical treatment of cryptorchidism have continued to evolve over the last 200 years. A study of the history of surgical management of the undescended testis sheds light on the rationale behind current management.


Whole genomic sequence of Enterobacter sichuanensis AJI 2411 - A plant growth promoting rhizobacteria.
Enterobacter sichuanensis AJI 2411 is a rhizobacteria displaying plant growth promoting potentials, which was isolated from the rhizosphere of soybeans in Ede, Osun State, Nigeria. The full genome of Enterobacter sichuanensis AJI 2411 was sequenced and reported in this study to shed light on the molecular mechanisms that aids the bacteria's plant growth-promoting abilities.