Isolation and characterization of microsatellite markers for Plathymenia reticulata (Fabaceae).
Microsatellite loci were isolated and characterized for use in population genetic studies of Plathymenia reticulata (Fabaceae), a tropical tree widespread in the Atlantic Forest and cerrado biomes of South America. Nine microsatellite markers were developed using a simple sequence repeat-enriched library. Polymorphism was analyzed in 51 individuals from two populations. All loci were polymorphic, with the number of alleles per loci ranging from five to 15 (mean number of alleles: 10.22). Observed and expected heterozygosities per loci and population ranged from 0.313 to 1.000 and 0.280 to 0.869, respectively. These highly informative loci are potentially useful to estimate population genetic structure and to understand evolutionary processes and taxonomy of the species.


Intestinal temperature, heart rate, and hydration status in multiday trail runners.
To assess heart rate (HR), intestinal body temperature (T(intest)), and hydration status changes and relationships in 12 participants in a 3-day trail run. Descriptive field study. : Three Cranes Challenge trail run, in Karkloof, KwaZulu-Natal, South Africa. Twelve (5 men and 7 women) amateur runners. Trail run of 95 km divided into 3 stages: elevation gains on the 3 days, 1020, 1226, and 680 m, respectively. Changes in HR, T(intest), serum osmolality, and body mass. Environmental conditions were consistently mild (ambient temperature range, 11.5-22.8°C; maximum relative humidity range, 95%-97%), average running speed varied from 9.00 to 5.14 minutes/km, and distance covered in the 3 stages ranged from 32 (stages 1 and 3) to 40 km (stage 2). Mean HR ranged from 134 to 171 beats per minute in the 12 athletes during the trail events and averaged at 150 beats per minute, whereas T(intest) ranged between 36.1 and 40.2°C. The correlation between maximum T(intest) and percent age-predicted maximum HR (n = 12) was significant (R = 0.58; P < 0.05), whereas the correlation between maximum T(intest) and serum osmolality or body mass did not reach significance (R = 0.16, 0.13; P > 0.05). This study provides evidence in support of the contention that maximum T(intest) is more closely related to metabolic rate during trail running than percent dehydration. The findings do not support an increase in core body temperature with a change in serum osmolality or body mass.


Comparative Study on Crack Initiation and Propagation of Glass under Thermal Loading.
This paper explores the fracture process based on finite element simulation. Both probabilistic and deterministic methods are employed to model crack initiation, and several commonly used criteria are utilized to predict crack growth. It is concluded that the criteria of maximum tensile stress, maximum normal stress, and maximum Mises stress, as well as the Coulomb-Mohr criterion are able to predict the initiation of the first crack. The mixed-mode criteria based on the stress intensity factor (SIF), energy release rate, and the maximum principal stress, as well as the SIF-based maximum circumferential stress criterion are suitable to predict the crack propagation.


Relationship between blood alcohol concentration and self-reported drinking behavior.
Men having a high blood alcohol concentration when arrested for drunken driving reported more drinking and more alcohol-related impairment than did men with lower concentrations.


The new cytogenetics: blurring the boundaries with molecular biology.
Exciting advances in fluorescence in situ hybridization and array-based techniques are changing the nature of cytogenetics, in both basic research and molecular diagnostics. Cytogenetic analysis now extends beyond the simple description of the chromosomal status of a genome and allows the study of fundamental biological questions, such as the nature of inherited syndromes, the genomic changes that are involved in tumorigenesis and the three-dimensional organization of the human genome. The high resolution that is achieved by these techniques, particularly by microarray technologies such as array comparative genomic hybridization, is blurring the traditional distinction between cytogenetics and molecular biology.


A Perspective on Wellness in Anesthesiology Residency Programs: A Multi-Strategy Approach.
Addressing resident wellness is an important topic given the high risk for burnout and depression in resident physicians compared with the general U.S. population. This article provides an overview of various approaches to help conceptualize and intervene on resident wellness, based on the 9-strategies framework to improve wellness laid out by Shanafelt and colleagues. This article outlines the most relevant literature in each strategy followed by the authors' experience within their anesthesiology residency program.


Differentiating diffuse from focal pattern on Computed Tomography in multiple myeloma: Added value of a Radiomics approach.
Focal pattern in multiple myeloma (MM) seems to be related to poorer survival and differentiation from diffuse to focal pattern on computed tomography (CT) has inter-reader variability. We postulated that a Radiomic approach could help radiologists in differentiating diffuse from focal patterns on CT. We retrospectively reviewed imaging data of 70 patients with MM with CT, PET-CT or MRI available before bone marrow transplant. Two general radiologist evaluated, in consensus, CT images to define a focal (at least one lytic lesion >5 mm in diameter) or a diffuse (lesions <5 mm, not osteoporosis) pattern. N = 104 Radiomics features were extracted and evaluated with an open source software. The pathological group included: 22 diffuse and 39 focal patterns. After feature reduction, 9 features were different (p < 0.05) in the diffuse and focal patterns (n = 2/9 features were Shape-based: MajorAxisLength and Sphericity; n = 7/9 were Gray Level Run Length Matrix (Glrlm)). AUC of the Radiologists versus Reference Standard was 0.64 (95 % CI: (0.49-0.78) p = 0.20. AUC of the best 4 features (MajorAxisLength, Median, SizeZoneNonUniformity, ZoneEntropy) were: 0.73 (95 % CI: 0.58-0.88); 0.71 (95 % CI: 0.54-0.88); 0.79 (95 % CI: 0.66-0.92); 0.68 (95 % CI: 0.53-0.83) respectively. A Radiomics approach improves radiological evaluation of focal and diffuse pattern of MM on CT.


Deficiency in IL-17-committed Vγ4(+) γδ T cells in a spontaneous Sox13-mutant CD45.1(+) congenic mouse substrain provides protection from dermatitis.
Interleukin 17 (IL-17)-committed γδ T cells (γδT17 cells) participate in many immune responses, but their developmental requirements and subset specific functions remain poorly understood. Here we report that a commonly used CD45.1(+) congenic C57BL/6 mouse substrain is characterized by selective deficiency in Vγ4(+) γδT17 cells. This trait was due to a spontaneous mutation in the gene encoding the transcription factor Sox13 that caused an intrinsic defect in development of those cells in the neonatal thymus. The γδT17 cells migrated from skin to lymph nodes at low rates. In a model of psoriasis-like dermatitis, the Vγ4(+) γδT17 cell subset expanded considerably in lymph nodes and homed to inflamed skin. Sox13-mutant mice were protected from psoriasis-like skin changes, which identified a role for Sox13-dependent γδT17 cells in this inflammatory condition.


Identification of the mammalian homologues of the Drosophila timeless gene, Timeless1.
We have identified novel mammalian homologues of a Drosophila clock gene, timeless, and designated them as human TIMELESS1 (hTIM1) and mouse Timeless1 (mTim1), respectively. These genes were mapped by FISH to chromosomal regions 12q12-13 in human and 10D3 in mouse. The deduced amino acid sequences of hTim1 and mTim1 proteins were 1208 and 1197 amino acids in length and shared 83% identity. Northern blot analysis identified a single transcript of 4.5 kb expressed widely in many tissues examined. Unlike the Drosophila counterpart, the levels of the mTim1 transcript exhibited no prominent circadian oscillation in the mouse brain.


Intrauterine expression of parathyroid hormone-related protein in normal and pre-eclamptic pregnancies.
Maternal hypertension, vasoconstriction and placental insufficiency are features of pre-eclampsia. Alterations in calcium homeostasis and in the production of calciotropic hormones and vasoactive agents have also been described in association with pre-eclampsia. Parathyroid hormone-related protein (PTHrP) is abundantly expressed in intrauterine tissues during normal pregnancy and has roles in fetal growth and calcium homeostasis, placental calcium transport and vascular tone regulation. Intrauterine PTHrP mRNA expression and tissue PTHrP content were determined by Northern blot analysis and radio-immunoassay, respectively, in preterm and term pre-eclamptic women. PTHrP mRNA expression and PTHrP content in placenta, amnion over placenta, reflected amnion and choriodecidua from preterm pre-eclamptic women (n=8-10) were not different from preterm controls (n= 10-12). PTHrP mRNA expression and content in amnion over placenta and reflected amnion were significantly greater in term compared to preterm pre-eclamptics (P<0.05). PTHrP mRNA expression was significantly lower in choriodecidua from term pre-eclamptic women (n=8) compared to term controls (n=28, P<0.05), but was not different in placenta or amnion. PTHrP content was not altered in term pre-eclamptic women (n=8) compared to controls (n=25) for any tissue. In summary, PTHrP expression in placenta and amnion was not increased in pre-eclamptic women in association with maternal hypertension, placental insufficiency and vasoconstriction. PTHrP mRNA expression was decreased in choriodecidua in association with term but not preterm pre-eclampsia, however, levels of the protein were not decreased. The data suggest that PTHrP is not involved in the placental pathophysiology of pre-eclampsia in late gestation.


Neurological abnormalities predict disability: the LADIS (Leukoaraiosis And DISability) study.
To investigate the role of neurological abnormalities and magnetic resonance imaging (MRI) lesions in predicting global functional decline in a cohort of initially independent-living elderly subjects. The Leukoaraiosis And DISability (LADIS) Study, involving 11 European centres, was primarily aimed at evaluating age-related white matter changes (ARWMC) as an independent predictor of the transition to disability (according to Instrumental Activities of Daily Living scale) or death in independent elderly subjects that were followed up for 3 years. At baseline, a standardized neurological examination was performed. MRI assessment included age-related white matter changes (ARWMC) grading (mild, moderate, severe according to the Fazekas' scale), count of lacunar and non-lacunar infarcts, and global atrophy rating. Of the 633 (out of the 639 enrolled) patients with follow-up information (mean age 74.1 ± 5.0 years, 45 % males), 327 (51.7 %) presented at the initial visit with ≥1 neurological abnormality and 242 (38 %) reached the main study outcome. Cox regression analyses, adjusting for MRI features and other determinants of functional decline, showed that the baseline presence of any neurological abnormality independently predicted transition to disability or death [HR (95 % CI) 1.53 (1.01-2.34)]. The hazard increased with increasing number of abnormalities. Among MRI lesions, only ARWMC of severe grade independently predicted disability or death [HR (95 % CI) 2.18 (1.37-3.48)]. In our cohort, presence and number of neurological examination abnormalities predicted global functional decline independent of MRI lesions typical of the aging brain and other determinants of disability in the elderly. Systematically checking for neurological examination abnormalities in older patients may be cost-effective in identifying those at risk of functional decline.


Development of the Japanese Version of the Psychosocial Assessment of Candidates for Transplantation in Allogeneic Hematopoietic Stem Cell Transplantation.
The Psychosocial Assessment of Candidates for Transplantation (PACT) is a validated instrument for evaluating psychosocial risk factors in transplant candidates. This study examined reliability and validity of the Japanese version of the PACT (J-PACT). PACT is a clinician-rated scale consisting of an initial rating, 8 subscales, and a final rating. J-PACT was developed through a translation and back-translation procedure. Seventy adult patients who underwent allogeneic hematopoietic stem cell transplant between April 2009 and December 2013 received retrospective J-PACT ratings based on medical records. Interrater reliability and concurrent validity with Hospital Anxiety and Depression Scale (HADS) and Profile of Mood Status (POMS) scores were assessed. Interrater reliability for each J-PACT item was generally high, ranging from 0.53 (drug and alcohol use)-0.93 (support stability). The concurrent validity analyses revealed the following significant relationships (p < 0.05). Higher support stability was associated with lower HADS depression (p = 0.02), POMS anger (p = 0.001), POMS fatigue (p = 0.03), and POMS confusion (p = 0.01) scores. Higher support availability was associated with lower POMS anger scores (p = 0.01). More suitable personality was associated with lower HADS anxiety (p = 0.04) and HADS depression (p = 0.048) scores. Better scores on lifestyle factors and alcohol use were both associated with lower POMS confusion scores (p = 0.01, 0.04, respectively). Better final rating was associated with lower HADS anxiety (p = 0.03) and HADS depression (p = 0.02) scores. J-PACT was reliable and valid, although further study is needed to confirm these findings.


Role of Sentinel Lymph Node Biopsy in Clinically Node Negative Carcinoma Penis - a Prospective Study.
Nodal metastasis is a strong prognostic indicator in carcinoma penis, with 25% difference in 5-year cancer-specific survival among node negative and node positive patients. This study aims to assess efficacy of SLNB in identifying occult nodal metastasis (seen in 20-25% of cases), thus avoiding morbidity of prophylactic groin dissection in rest. Study was conducted between June 2016 and December 2019 on 42 patients (84 groins). Primary outcomes assessed were sensitivity, specificity, false negative rates, positive predictive value, and negative predictive value of sentinel lymph node biopsy (SLNB) compared to superficial inguinal node dissection (SIND). Secondary outcomes were to know prevalence of nodal metastasis, sensitivity, specificity, false negative rates, positive predictive value (PPV), negative predictive value (NPV) of frozen section study, and ultrasonography (USG) compared to histopathological examination (HPE) and to evaluate false negative results of fine needle aspiration cytology (FNAC). Patients with impalpable inguinal nodes were subjected to USG and FNAC of suspicious nodes. Only those with non-suspicious USG/negative FNAC were included. Patients who were node positive, had prior chemotherapy/radiotherapy/prior groin surgery, or medically unfit for surgery were excluded. Dual-dye technique was used to identify sentinel node. Superficial inguinal dissection was done in all cases and both specimens were subject to frozen section. If ≥ 2 nodes were involved on frozen section, ilioinguinal dissection was done. SLNB had sensitivity, specificity, PPV, NPV, and accuracy of 100%, respectively. There were no false negative results of frozen section study among 168 specimens. Ultrasonography had sensitivity of 50%, specificity of 48.75%, PPV of 4.65%, NPV of 95.12%, and accuracy of 48.81%. We had 2 false negative results of FNAC. Sentinel node biopsy with frozen section study when done in properly selected cases using dual-dye technique in high volume centers by experienced professionals is a very reliable tool in establishing the nodal status, thereby facilitating need directed treatment, thus prevent either over/under treatment.


Oesophageal atresia: a simplified approach to early management.
Management following the repair of oesophageal atresia (OA) with tracheooesophageal fistula (TOF) in the past included the routine use of an intercostal chest drain, a gastrostomy, or a transanastomotic tube (TAT) for enteral nutrition and a routine contrast swallow (CS) before oral feeds. There has been a trend towards simplification of the management, but this is not universal. The aim of this study was to evaluate the safety of a simplified management regime in infants undergoing primary repair of OA in a retrospective case note review of infants undergoing surgery for OA with TOF under the care of one consultant over a 12-year period. Intercostal chest drains, TATs, and CSs were not routinely used. Early enteral feeding was initiated and oral feeding was allowed in babies of adequate birth weight (BW) and gestation. A CS was only performed when there were specific anastomotic concerns. Parameters recorded included demographic details, time to first enteral feed by tube or mouth, time to full oral feeds, and complications. Forty patients were studied; 17 were managed without (group 1) and 23 with (group 2) a TAT. Sex distribution, gestational age, and BW were comparable in the two groups. In group 1, the time to the establishment of full oral feeds was 2-8 days (average 3.9). Four infants developed strictures; 2 were managed with dilatation alone and 2 required surgery. In group 2, the time to the establishment of full enteral feeds was 2-12 days (average 5.9). Four patients developed strictures; 2 underwent an anti-reflux procedure and a 3rd resection of a cartilaginous remnant. There was 1 death in a patient with intractable cardiac failure. The majority of infants with OA and TOF can thus be safely managed without routine chest drainage or CS. A sizeable minority do not require a TAT. Early introduction of oral feeds in the non-TAT group is not associated with an increased complication rate.


Analysis of DNA sequences homologous with the ARS core consensus in Saccharomyces cerevisiae.
We have previously identified an autonomously replicating segment (ARS) near the 3' end of the histone H4 gene at the copy-I H3-H4 locus. We have now searched for additional autonomously replicating segments and sequences homologous with the ARS core consensus sequence near the copy-II histone H4 gene and both of the histone H3 genes. No new ARS elements were identified by functional cloning assays. However, several matches to the ARS core consensus element were found within the DNA sequences of the copy-I and copy-II genes. An exact match to the ARS core consensus was identified in the region downstream from the copy-I histone H3 gene and a set of sequences with weak homology was also located within the copy-II region. However, restriction fragments including these sequences did not demonstrate ARS activity on a plasmid in transformed cells.


Factors associated with changes in plantar pressure of people with peripheral diabetic neuropathy.
Diabetic neuropathy is one of the main complications of Diabetes Mellitus, which can lead to loss of protective sensation, motor, and plantar pressure alteration, generating deformities, abnormal gait and mechanical trauma to the feet. to evaluate the distribution of plantar pressure, sensorimotor changes, balance and associated factors to plantar pressure changes in people with peripheral diabetic neuropathy. Cross-sectional study conducted with individuals registered in the primary public health service of a city in the east of São Paulo - Brazil. The sample was composed by people with Diabetes Mellitus and Peripheral Neuropathy identified by the Michigan Screening Instrument. It were investigated variables such as sensory-motor changes, static and dynamic plantar pressure using baropodometry and balance using the Berg scale. A significance level of 5% was adopted for all tests used. Of the 200 individuals evaluated, 52.55% had no plantar protective sensitivity, the static evaluation did not demonstrated changes in the peak of plantar pressure, however in the dynamics the mean in the right foot was 6.0 (±2) kgf/cm2 and 6,7 (±1.62) kgf/cm2 on the left foot, the center of static pressure on the right foot was lower (10.55 ± 3.82) than on the left foot (11.97 ± 3.90), pointing hyper plantar pressure. The risk of falling was high, ranging from 8 to 56 points, with an average of 40.9 (±10.77). The absence of protective plantar sensitivity, increased pressure, biomechanical changes lead to loss of balance and are predictive of complications in the feet due to diabetic neuropathy.


Youth Experience Tracker Instrument: A self-report measure of developmental antecedents to severe mental illness.
We sought to examine the structure, internal consistency, convergent and criterion validity of the Youth Experience Tracker Instrument (YETI), a new brief self-report measure designed to facilitate early identification of risk for severe forms of mental illness, including major depressive disorder, bipolar disorder, and schizophrenia. We collected 716 YETIs from 315 individuals aged 8 to 27 with and without familial risk of severe mental illness. The YETI measures six developmental antecedents that precede and predict serious forms of mental illness: affective lability, anxiety, basic symptoms, depressive symptoms, psychotic-like experiences, and sleep. A battery of concurrent questionnaires and interviews measured the same constructs. The best-fitting bifactor model supported the validity of both total score and antecedent-specific subscales. Internal consistency was high for the total score (ω = 0.94) and subscales (ω = 0.80-0.92; ρ = 0.72). The total score captured the majority of information from the 26 YETI items (hierarchical omega ωh = 0.74). Correlations of YETI subscales with established measures of the same constructs (r = 0.45-0.80) suggested adequate convergent validity. We propose cut-offs with high negative predictive values to facilitate efficient risk screening. The YETI, a brief self-report measure of antecedents, provides an alternative to using multiple longer instruments. Future research may examine the predictive validity of the YETI for the onset of major mood and psychotic disorders.


Quantitative immunoelectrophoretic analysis of rat allergen extracts. I. Antigenic characterisation of fur, urine, saliva and other rat-derived materials.
Crossed immunoelectrophoresis reference patterns were established for the antigenic constituents of rat fur, urine and saliva. Using quantitative immunoelectrophoretic techniques, extensive cross-reactivity was observed between these extracts, and with epithelia, shaved pelt, serum, faeces and dust. No major qualitative sex differences were observed, though levels of certain components differed. Constituents of many source materials were found to show a reaction of partial identity with previously isolated rat urinary allergens; and relative skin test reactivity of a range of these extracts was associated with the amount of urinary allergen present. Material from two different rat strains had similar constituents. Rat source materials did not cross-react with the corresponding extracts from guinea pigs.


The size of educational differences in mortality from specific causes of death in men and women.
This study examines the association between education and mortality from specific causes of death based on mortality records for 1996 and 1997, and 1996 population census data from the Region of Madrid (Spain). Poisson regression models were used to estimate the percentage increase in mortality associated with 1 year less education. The percentage increases in mortality from stomach cancer, lung, bladder and liver cancers, for aids, chronic obstructive pulmonary disease, pneumonia and influenza, and chronic liver disease and cirrhosis were higher in men than in women, whereas the percentage increases in mortality from colon cancer, diabetes mellitus, ischemic heart disease and nephritis, nephrosis and nephrotic syndrome were higher in women. The results found for some causes of death--lung cancer, ischemic heart disease, diabetes mellitus and chronic obstructive pulmonary disease--reflect the variations by educational level in the prevalence of lifestyle-related risk factors in men and women. Various hypotheses have been suggested for other causes of death, but it is not known why the magnitude of the association between education and mortality from some causes of death differs between men and women. Future studies of this subject may provide some clues as to the underlying mechanisms of this association.


Photodynamic therapy improves the outcome of immune checkpoint inhibitors via remodelling anti-tumour immunity in patients with gastric cancer.
Photodynamic therapy (PDT) plays an immunoregulatory role in tumours. Here, we conducted a retrospective patient analysis to evaluate the effectiveness of PDT plus immune checkpoint inhibitors (ICIs) in gastric cancer. Further, we performed a dynamic analysis of gastric cancer patients receiving PDT to clarify its effects on anti-tumour immunity. Forty ICI-treated patients that received PDT or not were retrospectively analysed. Five patients with gastric adenocarcinoma were enrolled for sample collection before and after PDT. Single-cell RNA/T cell receptor (TCR) sequencing, flow cytometry and histological exanimation were used to analyse the collected specimens. Patients in PDT group had a significantly better OS after ICI treatment than those in No PDT group. Single-cell analysis identified ten cell types in gastric cancer tissues and four sub-populations of T cells. Immune cell infiltration increased in the tumours after PDT and the circular immune cells showed consistent alterations. TCR analysis revealed a specific clonal expansion after PDT in cytotoxic T lymphocytes (CTL), but a constriction in Tregs. The B2M gene is upregulated in tumour cells after PDT and is associated with immune cell infiltration. Several pathways involving the positive regulation of immunity were enriched in tumour cells in the post-PDT group. The interactions following PDT were increased between tumour cells and effector cells but decreased between Tregs and other immune cells. Some co-stimulatory signaling emerged, whereas co-inhibitory signaling disappeared in intercellular communication after PDT. PDT elicits an anti-tumour response through various mechanisms and is promising as an adjuvant to enhance ICI benefit.


Effect of stabilization time and soil chromium concentration on Sesbania virgata growth and metal tolerance.
Sesbania virgata is a pioneer shrub from the Fabaceae family, native to riparian environments in northeast of Argentina, southern of Brazil and Uruguay. In peri-urban riparian soils, metal contamination is a frequent problem, being its bioavailability partly determined by the stabilization time and frequency of contamination events. The effect of time elapsed between chromium (Cr) soil enrichment and plant seeding and Cr doses on S. virgata tolerance and metal absorption were evaluated. Treatments were developed by adding Cr (80-400 ppm) to the soil and allowing two days or fifteen months to elapse before sowing, and a control treatment without Cr addition. After 150 days from seeding, bioaccumulation and translocation factors, growth parameters (dry biomass and its aerial/radical allocation pattern, stem length and its elongation rate), morphological parameters (root volume and leaf area), and physiological parameters (chlorophyll content) of the specimens were determined. The emergence of S. virgata was inhibited since 150 ppm when Cr was added to the soil two days before seeding, with Cr accumulation in roots starting at 80 ppm (17.4 ± 2.5 mg kg-1). Under 15 months of metal stabilization, S. virgata plants survived across the entire range of Cr doses tested, with accumulation in roots since 100 ppm (35.5 ± 0.2 mg kg-1) and metal translocation to aerial tissues only under 400 ppm. The results obtained showed that S. virgata did not have high BCF and TF values, suggesting that it cannot be classified as bioaccumulator of Cr under the tested conditions. However, its presence in environments contaminated with Cr can be beneficial, as it helps to stabilize the metal in the soil.


Nonfatal tractor-related injuries presenting to a state trauma system.
To identify tractor-related injuries using data from a statewide trauma system, to characterize the mechanisms of nonfatal tractor-related injury, and to determine which injuries are associated with higher severity injury. A retrospective observational study was conducted using the Iowa State Trauma Registry to identify cases of nonfatal tractor-related injuries over an 11-year period from 2002 to 2012. Frequency of injury was reported by age, sex, severity, and nature. Injuries were classified by mechanism and a polytomous regression model was used to predict injury severity adjusting for sex and age. Five-hundred thirteen nonfatal tractor-related injuries were identified with 18% classified as severe. Injuries were most frequent among males and among those ≥45years of age. Rollovers were the most frequent mechanism of both total (25%) and severe injury (38%), although the frequency of injury mechanism varied by age. Falls were the next most frequent mechanism of injury (20%) but resulted in fewer high-severity injuries. Collision (adjOR=1.89, 95% CI=1.01-3.51), rollover (adjOR=2.03, 95% CI=1.21-3.40), and run over/rolled on (adjOR=2.06, 95% CI=1.17-3.62) injuries were significantly associated with higher injury severity. Advanced age was also a significant predictor of higher severity injury (adjOR=1.82, 95% CI=1.06-3.12). Mechanisms of nonfatal tractor-related injuries are heterogeneous, differ by age, and are associated with varying level of severity. This work shows the burden of nonfatal tractor injuries on a rural state trauma system. These findings also demonstrate the heterogeneous nature of nonfatal tractor injuries and underscore the need for a multi-level approaches to injury prevention.


A database system for abstract selection for a major anesthesia society meeting.
Until the present time, record keeping for abstract selection for major anesthesia meetings has been performed by manual methods - paper, pen, and typewriter. We describe the construction and implementation of a microcomputer based system to facilitate data recording, form-letter generation, and program construction. Based on MicroPro's WordStar, InfoStar, MailMerge series, the database has reduced the total effort required to construct the final program from 1.5 hours per abstract submitted for the 1984 meeting to 0.7 hours for the 1986 meeting. Problems encountered were mastery of the system by operating personnel, floppy disk overflow, and data loss of unknown etiology. The significant time savings attest to the value of the system.


CARD14 Glu138 mutation in familial pityriasis rubra pilaris does not warrant differentiation from familial psoriasis.
Some familial cases of pityriasis rubra pilaris (PRP) have the CARD14 gene mutations that are also detected in familial psoriasis vulgaris. However, genotype-phenotype correlation in these two entities is poorly understood. Here, we report a case of PRP with a new mutation in CARD14. Genomic analysis of a 40-year-old female patient with sporadic PRP type V identified a heterozygous dominant c.412G>A mutation (p.Glu138Lys) in CARD14. Two types of CARD14 mutations causing Glu138 substitutions have been reported in cases of familial PRP and pustular psoriasis. All three types, including the present case, are predicted to cause similar loss of the negative charges at this site. This suggests that the difference in molecular charge and the resulting change in molecular interaction around the N-terminal end of the coiled-coil region of CARD14 molecule do not determine the phenotypic differences between psoriasis and PRP.


Dental sensory receptors.
Teeth are innervated by unmyelinated sympathetic axons, and by unmyelinated and small myelinated sensory axons. Some sensory axons in teeth are terminal branches of larger parent axons, so that conduction from teeth to CNS in trigeminal nerves includes C-fiber, A-delta, and A-beta velocities. Sensory dental axons contain acetylcholine or substance P-like immunoreactivity. The sympathetic axons contain noradrenalin. Other neuropeptides may also be present, such as vasoactive intestinal peptide and serotonin. Dental axons of mature teeth of many species (man, monkey, cat, rodents, fish) are essentially the same, but continuously erupting teeth have smaller and fewer axons. Free sensory nerve endings in mature teeth are found in the peripheral plexus of Raschkow, the odontoblastic layer, the predentin, and the dentin. Free nerve endings are most numerous in those regions near the tip of the pulp horn, where more than 40% of the dentinal tubules can be innervated. Many dentinal tubules contain more than one free nerve ending. Intradentinal axons can extend as far as 0.2 mm into dentin but usually end less than 0.1 mm from the pulp. Some sensory endings also occur along pulpal blood vessels. In continuously erupting teeth nerve endings do not enter the dentin but remain within the pulp. Nerve endings in dentin are labeled by axonal transport. They are therefore as viable and active as the nerve endings in pulp. The axoplasm of the free nerve endings contains organelles typical of other somatosensory receptors. These organelles are most common in the successive beaded regions along the free nerve endings and include mitochondria, clear and dense-core vesicles, multivesicular bodies, profiles of smooth endoplasmic reticulum, and relatively few microtubules and neurofilaments. The beads can vary in size from about 0.2 to 2.0 microns and can have varying amounts of receptor organelles. The interbead axonal regions are thin and contain mainly microtubules and neurofilaments. Nerve endings are associated with companion cells after they leave the coronal nerve bundles; these companion cells include Schwann cells, fibroblasts, and odontoblasts. There is no good evidence of gap junctions or synapses between nerve endings and odontoblasts. Instead, the two cell types form appositions that have a 20-40 nm extracellular cleft and parallel apposed plasmalemmas but no unusual membrane-associated material. No special organelles occur in the odontoblastic cytoplasm at these sites.(ABSTRACT TRUNCATED AT 400 WORDS)


Rigid bronchoscopy and mechanical debulking in the management of central airway tumors: an Indian experience.
Treatment options for central airway tumors include surgery, radiotherapy, and in those with inoperable or emergent airway obstruction, therapeutic bronchoscopy. Herein, we report our experience with the exclusive use of rigid bronchoscope in the management of central airway tumors. Retrospective review of charts of patients who underwent rigid bronchoscopy and mechanical coring for the management of central airway (trachea and mainstem bronchi) tumors over a period of 2 years. "Successful" outcome was defined as procedure leading to reduction of luminal obstruction to <50% and improvement of respiratory distress. "Unsuccessful" outcome was defined in cases where the luminal obstruction could not be reduced by ≥50% or there was lack of improvement in the clinical status of the patient. During the study period, 30 patients with symptomatic central airway tumors were encountered. Of these, 23 patients underwent 31 rigid bronchoscopic procedures. Respiratory failure was present in 15 (65.2%) patients. Adenoid cystic carcinoma was the most common primary tracheal tumor, whereas squamous cell carcinoma was the most common secondary tracheobronchial tumor. The procedure was successful in 19 (82.6%) patients. Complications were encountered in 10 of the 31 (32.3%) rigid bronchoscopies. There was no procedural mortality. Rigid bronchoscopy and mechanical debulking as a sole therapy is an effective and safe procedure for airway obstruction resulting from tracheobronchial tumors.


High performing primary health care organizations from patient perspective: a qualitative study in China.
There is a global call to build people-centred primary health care (PHC) systems. Previous evidence suggests that without organization-level reform efforts, the full potential of policy reforms may be limited. This study aimed to generate a profile of high performing PHC organizations from the perspective of patients. We conducted semi-structured interviews with 58 PHC users from six provinces (Shandong, Zhejiang, Shaanxi, Henan, Shanxi, Heilongjiang) in China using purposive and snowball sampling techniques. Transcription was completed by trained research assistants through listening to the recordings of the interviews and summarizing them in English by 30-s segments to generate the narrative summary. Informed by the Classification System of PHC Organizational Attributes, thematic analysis aimed to identify domains and attributes of high performing PHC organizations. A profile of a high performing PHC organization with five domains and 14 attributes was generated. The five domains included: (1) organizational resources including medical equipment, human and information resource; (2) service provision and clinical practice including practice scope, internal integration and external integration; (3) general features including location, environment and ownership; (4) quality and cost; and (5) organizational structure including continuous learning mechanism, administrative structure and governance. A five-domain profile of high performing PHC organizations from the perspective of Chinese PHC users was generated. Organizational resources, service delivery and clinical practices were most valued by the participants. Meanwhile, the participants also had strong expectation of geographical accessibility, high quality of care as well as efficient organizational structure. These organizational elements should be reflected in further reform efforts in order to build high performing PHC organizations.


Conservative Curative Larynx Preserving Surgery for Subglottic Soft Tissue Recurrence Reinforced with Fascia-Lata and Strap Muscles.
For early cancers of vocal cords, trans oral laryngeal surgery (TOLS) and curative radiotherapy (RT), have remained mainstay of treatment. Soft tissue recurrence in laryngeal cancers is not much documented, leading to absence of guidelines to deal with it, salvage total laryngectomy being the treatment of choice. We present a tailormade surgical procedure for limited soft tissue recurrence of glottic cancer extending into subglottic anterior soft tissue reinforced with fascia lata and strap muscles, previously treated with TOLS and/or RT.


Simultaneous effects of two fungicides (copper and dimethomorph) on their phytoremediation using Lemna minor.
Effects of two fungicides, copper and dimethomorph ((E,Z)4-[3-(4-chlorophenyl)-3-(3-4dimethoxyphenyl) acryloyl] morpholine) on Lemna minor growth and phytoremediation were evaluated. The toxicity of copper and dimethomorph alone and in combination, was assessed by growth inhibition of L. minor cultures after 96 and 168 h. Copper had a severe impact on growth (max. inhibition: 90 % at 1,000 μg L(-1)) while dimethomorph (as pure ingredient or formulated as Forum) did not (inhibition <45 % at 1,000 μg L(-1)) after 168 h of treatment. When both chemicals were combined, synergism was observed after 96 h of exposure to copper and Forum. However, this interaction was a simple additivity after 168 h. Additivity was also observed when the pure active ingredient (dimethomorph) replaced Forum in the mixture of copper and dimethomorph at 96 and 168 h. L. minor showed an excellent performance in removing copper from the medium since after 96 h, 36, 60, and 76 % removal were reached for 10, 20, and 30 μg L(-1) of Cu respectively. Copper accumulated in the plants. The removal of copper increased with Forum concentration. After 96 h copper (10 μg L(-1) initial concentration) elimination increased from 36.39 ± 5.86-60.70 ± 6.06 % when Forum concentration increased from 0 to 500 μg L(-1). Accumulation of copper in plants was also increased by Forum but not by the active ingredient alone. Depuration of Forum by L. minor varied between 10 and 40 % after 96 h and it was generally more efficient than that of the pure ingredient. This depuration decreased in the presence of copper possibly due to the metal toxicity.


Partial purification and characterization of the first hydrogenase isolated from a thermophilic sulfate-reducing bacterium.
A soluble [NiFe] hydrogenase has been partially purified from the obligate thermophilic sulfate-reducing bacterium Thermodesulfobacterium mobile. A 17% purification yield was obtained after four chromatographic steps and the hydrogenase presents a purity index (A398 nm/A277 nm) equal to 0.21. This protein appears to be 75% pure on SDS-gel electrophoresis showing two major bands of molecular mass around 55 and 15 kDa. This hydrogenase contains 0.6-0.7 nickel atom and 7-8 iron atoms per mole of enzyme and has a specific activity of 783 in the hydrogen uptake reaction, of 231 in the hydrogen production assay and of 84 in the deuterium-proton exchange reaction. The H2/HD ratio is lower than one in the D2-H+ exchange reaction. The enzyme is very sensitive to NO, relatively little inhibited by CO but unaffected by NO2-. The EPR spectrum of the native hydrogenase shows the presence of a [3Fe-4S] oxidized cluster and of a Ni(III) species.


Activatable MRI probes for the specific detection of bacteria.
Activatable fluorescent probes have been successfully used as molecular tools for biomedical research in the last decades. Fluorescent probes allow the detection of molecular events, providing an extraordinary platform for protein and cellular research. Nevertheless, most of the fluorescent probes reported are susceptible to interferences from endogenous fluorescence (background signal) and limited tissue penetration is expected. These drawbacks prevent the use of fluorescent tracers in the clinical setting. To overcome the limitation of fluorescent probes, we and others have developed activatable magnetic resonance probes. Herein, we report for the first time, an oligonucleotide-based probe with the capability to detect bacteria using magnetic resonance imaging (MRI). The activatable MRI probe consists of a specific oligonucleotide that targets micrococcal nuclease (MN), a nuclease derived from Staphylococcus aureus. The oligonucleotide is flanked by a superparamagnetic iron oxide nanoparticle (SPION) at one end, and by a dendron functionalized with several gadolinium complexes as enhancers, at the other end. Therefore, only upon recognition of the MRI probe by the specific bacteria is the probe activated and the MRI signal can be detected. This approach may be widely applied to detect bacterial infections or other human conditions with the potential to be translated into the clinic as an activatable contrast agent.


[Study of the somatotropic function of the pituitary gland and the glucocorticoid function of the adrenal glands in rats with alloxan diabetes].
The somatotropichormone (STH) content was studied in the hypophysis and the peripheral blood of rats with alloxan diabetes; the corticosterone content was determined in their peripheral blood. The STH content in the peripheral blood and the hypophysis of these rats failed to differ from that in the control group, but the blood STH content rose considerably in the sick animals. Exclusion of the insular apparatus function was accompanied by the adrenal gland hypertrophy, which correlated with the rise of the blood corticosterone level. The data obtained indicated that the insular apparatus insufficiency induced by alloxan was accompanied by changes in the somatotropic function of the hypophysis and of glucocorticoid function of the adrenal glands.


Percutaneous trans-ulnar versus trans-radial arterial approach for coronary angiography and angioplasty, a preliminary experience at an Egyptian cardiology center.
Trans-ulnar approach was proposed primarily for elective procedures in patients not suitable for trans-radial approach that was introduced two decades ago. The trans-ulnar approach is as safe and effective as the trans-radial approach for coronary angiography and intervention. This study's aim was to assess the feasibility and safety of the trans-ulnar approach in coronary procedures as a preliminary experience for operators experienced in trans-radial approach with no/minimal trans-ulnar approach experience at an Egyptian center. Vascular access in 120 patients was selected randomly for coronary angiography and angioplasty-80 through radial and 40 through ulnar approach. Patients were examined for local complications and Doppler evaluation to both radial and ulnar arteries a day after the procedure was done. Ulnar approach success was 82.5% versus 93.7% in the radial group; failure of ulnar artery puncture was the only cause of crossover in the ulnar group, while occurrence of persistent spasm was the leading cause of crossover in the radial group followed by radial artery tortuosity. The procedure time of coronary angiography and percutaneous coronary intervention of the ulnar group was significantly higher than that of the radial group (P value = 0.011 and 0.034, respectively). The mean caliber of the right ulnar artery was 2.45 ± 0.38, slightly larger than that of the radial artery 2.33 ± 0.38 at the level of the wrist, but this difference was statistically non-significant. Our study demonstrated that ulnar access with experienced radial operators and in our patients is a safe and practical approach for coronary angiography or angioplasty, without any major complications. Bearing in mind its high success rate, it can be used when a radial artery is not useful for the catheterization or as a default approach on the expense of slightly longer procedural time.


Can chronic kidney disease lead to chronic heart failure, and does worsening chronic heart failure lead to chronic kidney disease progression.
The objective of this review is to discuss if chronic kidney disease (CKD) leads to chronic heart failure (CHF), and does worsening CHF lead to CKD progression and how a new medication class can modify the risk of both outcomes. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are similarly effective on cardiovascular (CV) - and kidney-related outcomes in the presence of CV and CKD. SGLT2 inhibitors can reduce the risk of CHF events and CKD progression, and may have synergistic effects in patients with cardiorenal syndrome.


Exposure to acetamiprid influences the development and survival ability of worker bees (Apis mellifera L.) from larvae to adults.
In most cases, honey bees experience pesticide pollution in a long-term period through direct or indirect exposure, such as the development process from larvae to the pre-harvest stage. At present, little is known about how honey bees respond to pesticide stresses during the continuous development period. This study aims to examine effects of long-term acetamiprid exposure on the development and survival of honey bees, and further present the expression profile in larvae, 1-day-old, and 7-day-old adult worker bees that related to immune, detoxification, acetylcholinesterase (AChE) and memory. Honey bees from 2-day-old larvae to 14-day-old adults except the pupal stage were continuously fed with different acetamiprid solutions (0, 5, and 25 mg/L). We found that acetamiprid over 5 mg/L disturbed the development involving birth weight and emergence rate of newly emerged bees, and reduced the proportion of capped cells of larvae at 25 mg/L; gene expression related to immune and detoxification of worker bees exposed to acetamiprid was roughly activated, returned and then inhibited from larval to emerged and to the late adult stage, respectively. Moreover, lifespans of bees treated with acetamiprid at 25 mg/L were significantly reduced. The present study reflects the potential risk for honey bees continuously exposed to acetamiprid in the development stage.


2,9,10-Trimeth-oxy-dibenzo[b,d]oxepin-7(6H)-one.
The title compound, C(17)H(16)O(5), was prepared through a cyclization reaction of 2-(3',4',5-trimeth-oxy-biphenyl-2-yl-oxy)acetyl chloride. The two benzene rings form a dihedral angle of 34.55 (5)°. The crystal structure does not feature any hydrogen bonds.


A quantitative comparison of the early histopathological changes from tracheotomy and endotracheal intubation on the distal trachea in fetal lambs.
Twenty-four premature fetal lambs underwent tracheotomy (n = 11) or endotracheal intubation (n = 13) for 3-9 h for an unrelated experiment. All were maintained with 100% oxygen on a pressure cycled ventilator. No suctioning was performed. At sacrifice, sections of the distal trachea were studied for histopathological changes in epithelium, submucosa and mucous glands. All changes were confined to the epithelium and were reported as either partial or total epithelial erosion in regards to preservation of the basal cell layer. In tracheotomized and intubated animals, both partial and total erosion were seen as early as 3 and 3.5 h, respectively. In the intubated animals, 13.5% of the cumulative tracheal circumference showed total erosion; 19.8% showed partial erosion. In animals undergoing tracheotomy, 9.6% of the cumulative tracheal circumference had total erosion; 19.1% had partial erosion. Possible etiological factors include oxygen toxicity, lack of humidification, effects of mechanical ventilation and indirect trauma from surgery or intubation. The clinical significance for premature infants is discussed.


Alpha-2-adrenoceptor sensitivity in early alcohol withdrawal.
Growth hormone (GH), blood pressure, and pulse rate responses to clonidine (100 micrograms IV) were studied three times during the first week of alcohol withdrawal in 19 alcohol-dependent patients. Fifteen healthy men were used as controls. The results suggest reduced sensitivity of the alpha-2-adrenoceptors involved in GH secretion for at least 1 week after the end of alcohol intake. In contrast, very short-lasting subsensitivity was found in the alpha-2-adrenoceptors regulating blood pressure.


A gene for Stargardt's disease (fundus flavimaculatus) maps to the short arm of chromosome 1.
Stargardt's disease (fundus flavimaculatus) is one of the most frequent causes of macular degeneration in childhood and accounts for 7% of all retinal dystrophies. It is an autosomal recessive condition characterized by a bilateral loss of central vision occurring at age 7-12 years. Genetic linkage analysis of eight families has assigned the disease locus to chromosome 1p21-p13. Multipoint linkage analysis and haplotype analysis has allowed us to establish the best estimate for location of the gene over the locus D1S435 (maximum lod score of 12.66). Our results are consistent with the genetic homogeneity of this condition.


The effect of intravenous lipids on gastric emptying in rats subjected to total parenteral nutrition.
Total parenteral nutrition (TPN) is indicated in a number of clinical situations involving obstructive disorders of the gastrointestinal tract or when total bowel rest is required. However, little is known of its effects upon the physiology of gastric storage and emptying. A study of the effects of lipid nutrient content of TPN on the gastric emptying of a non-energy liquid test meal in male and female conscious rats (250-280 g) was undertaken. Five experimental groups were set up according to the percentage of total non-protein energy administered in the form of different lipids: A (lipid-free: 100% of non-protein energy as glucose); B (5% long-chain triglycerides (LCT), 95% glucose); C (40% LCT, 60% glucose); D (5% LCT and medium-chain triglycerides (MCT) in 1:1 proportion, 95% glucose); and E (40% LCT and medium-chain triglycerides (MCT) in 1:1 proportion, 60% glucose). Animals were maintained on TPN for 24 h and for 3 and 4 days, after which gastric emptying was measured by the phenol red method. 40% lipid TPN was found to accelerate gastric emptying as infusion was prolonged, although the type of lipid had no effect.


Repair of descending thoracic aortic dissection or aneurysm combined with repair of the proximal aorta via median sternotomy.
A single-stage procedure for repair of the whole thoracic aorta via median sternotomy is described. The procedure is based on exposure of the descending aorta, posterior to the pericardium in the oblique sinus, or exposure of the aorta in the supracoeliac region and the placement of an endoprosthesis as an intraluminal graft. The ascending aorta and arch repair can be carried out as usual. The procedure has been performed in five patients with either dissection or aneurysm in the period between 1992 and 1997.


"Burns Behind Bars": A 10-year review and cost analysis of burn injuries in prison inmates presenting to a regional burns centre, and the role of the burns outreach service.
From 85348 inmates in England and Wales, over 26,000 incidents of assault and 40,000 of self-harm were reported from within prisons in 2016. This study focuses primarily on burn injuries in prison, determining the predominant aetiology as well as clinical outcomes of these injuries. Data was retrieved retrospectively and a case series performed, including all burns referred from regional prisons to our centre from 2007 to 2017 and comprising patient demographics, mechanism of injury, total body surface area affected, management, and outcome. Cost analysis of care was conducted using a previously published framework. 18 cases from three regional prisons were recorded, with 67% from a single prison. Referrals rose exponentially over time, with 44% occurring in 2017. 94% were scald burns, and 56% secondary to assault, primarily through the use of kettles and mostly targeting the face and trunk. The mean TBSA of burn was 2.89% (<1-8%), and 80% received first aid. 72.2% were admitted to hospital for an average of 4 days. All burns were managed nonoperatively with dressings and underwent on average 2 outpatient reviews (1-8). The disproportionate spread of referrals across the prisons correlates partly with the respective populations, but may also represent contrasting medical provisions. The recurring method of assault reflects the relative ease of access to hot water as a harmful agent, predominantly presenting with scalds affecting more critical areas, and with concurrent physical trauma in nearly half of cases which presents management challenges. Targeted education is recommended to reduce the incidence and ensure adequate management of burns in prison, referrals for which are demonstrably rising. Accordingly, the Burns Outreach team can provide training to in-house prison health staff and review referrals to specialist Burns services, aiming to ensure equitable care while alleviating costs associated with transfer to and management in hospital.


Additional mutations in SRSF2, ASXL1 and/or RUNX1 identify a high-risk group of patients with KIT D816V(+) advanced systemic mastocytosis.
Most patients with KIT D816V(+) advanced systemic mastocytosis (SM) are characterized by somatic mutations in additional genes. We sought to clarify the prognostic impact of such mutations. Genotype and clinical characteristics of 70 multi-mutated KIT D816V(+) advanced SM patients were included in univariate and multivariate analyses. The most frequently identified mutated genes were TET2 (n=33 of 70 patients), SRSF2 (n=30), ASXL1 (n=20), RUNX1 (n=16) and JAK2 (n=11). In univariate analysis, overall survival (OS) was adversely influenced by mutations in SRSF2 (P<0.0001), ASXL1 (P=0.002) and RUNX1 (P=0.03), but was not influenced by mutations in TET2 or JAK2. In multivariate analysis, SRSF2 and ASXL1 remained the most predictive adverse indicators concerning OS. Furthermore, we found that inferior OS and adverse clinical characteristics were significantly influenced by the number of mutated genes in the SRSF2/ASXL1/RUNX1 (S/A/R) panel (P<0.0001). In conclusion, the presence and number of mutated genes within the S/A/R panel are adversely associated with advanced disease and poor survival in KIT D816V(+) SM. On the basis of these findings, inclusion of molecular markers should be considered in upcoming prognostic scoring systems for patients with SM.


Micropercutaneous versus Retrograde Intrarenal Surgery for the Management of Moderately Sized Kidney Stones: A Systematic Review and Meta-Analysis.
To compare the effect of micropercutaneous surgery (microperc) and retrograde intrarenal surgery (RIRS) in the management of moderately size kidney stones. A systematic literature search was conducted in March 2019 using PubMed, Google Scholar, Web of Science, Embase, the Cochrane Library, and Medline to identify relevant studies. A subgroup analysis was performed to compare microperc with RIRS in patients with lower-pole stones (LPS) and non-LPS (NLPS), respectively. Three randomized controlled trials (RCTs) and 4 non-RCTs were analyzed. Microperc provided a significantly lower rate of double-J stent insertion (p < 0.00001) but a larger decrease in hemoglobin levels (p = 0.0002). In contrast, RIRS led to a shorter hospital stay (p = 0.01) and a lower stone-free rate (SFR) (p = 0.03). IN the subgroup analysis, RIRS provided a significantly lower drop in hemoglobin drop than microperc in patients with LPSs (p = 0.0003). Microperc showed a longer operative time (p = 0.03), longer hospital stay (p = 0.04), and greater drop in hemoglobin (p = 0.04) in patients with NLPS. Microperc is associated with fewer double-J stent insertions and higher SFR at the expense of a greater drop in hemoglobin and longer hospital stay. Given the differences between the procedures, urologists should synthesize the individual characteristics of patients and unique advantages of these therapies so as to choose the optimal treatment for individual patients.


Intense stimulated Raman scattering in CO2-filled hollow-core fibers.
We demonstrate experimentally, the generation of an intense broadband comb-like spectrum spontaneously built up through stimulated Raman scattering in a low-pressure CO2-filled hollow-core photonic crystal fiber pumped by a single infrared pump.


The effect of chronic tianeptine administration on the brain mitochondria: direct links with an animal model of depression.
A growing body of evidence has focused on the impact of mitochondrial disturbances in the development of depression, but little data exist regarding the effects of chronic administration of antidepressant drugs on the brain's mitochondrial protein profile. The aim of this study was to investigate the impact of chronic treatment with an atypical antidepressant drug-tianeptine-on the mitochondria-enriched subproteome profile in the hippocampus and the frontal cortex of 3-month-old male rats following a prenatal stress procedure. Rats that were exposed to a prenatal stress procedure displayed depressive- and anxiety-like disturbances based on the elevated plus-maze and Porsolt tests. Moreover, two-dimensional electrophoresis coupled with mass spectrometry showed structure-dependent mitoproteome changes in brains of prenatally stressed rats after chronic tianeptine administration. A component of 2-oxoglutarate and succinate flavoprotein subunit dehydrogenases, isocitrate subunit alpha, was upregulated in the hippocampus. In the frontal cortex, there was a striking increase in the expression of glutamate dehydrogenase and cytochrome bc1 complex subunit 2. These findings suggest that mitochondria are underappreciated targets for therapeutic interventions, and mitochondrial function may be crucial for the effective treatment of stress-related diseases.


Humoral immunity after second dose of BNT162b2 vaccine in Japanese communities: an observational cross-sectional study, Fukushima Vaccination Community Survey.
To reveal waning humoral immunity after second dose BNT162b2 vaccinations in a rural Japanese community and determine factors affecting antibody titers. We aimed to report Immunoglobulin G (IgG) antibody against the SARS-CoV-2 spike (S1) protein levels and neutralizing activity in a large scale community based cohort. Participants in the observational cross-sectional study received a second dose of vaccination with BNT162b2 (Pfizer/BioNTech) and were not previously infected with COVID-19. Questionnaire-collected data on sex, age, adverse vaccine reactions, and medical history was obtained. Data from 2496 participants revealed that older age groups reached a low antibody titer 90-120 days after the second vaccination. Neutralizing activity decreased with age; 35 (13.3%) of those aged ≥ 80 years had neutralizing activity under the cut-off value. Neutralizing activity > 179 days from the second vaccination was 11.6% compared to that at < 60 days from the second vaccination. Significantly lower IgG antibody titers and neutralizing activity were associated with age, male sex, increased time from second vaccination, smoking, steroids, immunosuppression, and comorbidities. Antibody titer decreased substantially over time. Susceptible populations, older people, men, smokers, steroid users, immunosuppression users, and people with three or more comorbidities may require a special protection strategy.


Failure of thromboprophylaxis in pregnancy caused by dual deficiencies of protein S and protein C.
Protein S and protein C deficiencies are commonly identified biochemical abnormalities associated with a hypercoagulable state; they result in an increased incidence of venous thromboembolism. We report the case of a pregnant woman with dual deficiencies of protein S and protein C, who encountered a venous thromboembolism 7 days postpartum despite of the use of danaparoid.


[Comparison of treatments in patients with inoperable stage IV advanced esophageal cancer].
The aim of this study was to compare palliative treatments such as chemotherapy, chemoradiotherapy or radiotherapy with best supportive care in patients with inoperable advanced esophageal cancer. A total of 67 patients with inoperable advanced esophageal cancer visiting Kosin University Gospel Hospital between January 2000 and July 2010 were included in a retrospective analysis. Patients were categorized as having palliative treatment or best supportive care to compare their prognosis. The median survival was 6.4 months in 67 patients. There was significant difference in median survival between the palliative and best supportive treatment (9.8 months vs. 4.5 months, p=0.01). The patients who underwent palliative treatment had superior 1-year and 3-year overall survival rate than those with best supportive treatment (27%, 10% vs. 5%, 5%, respectively). The 1-year and 3-year overall survival rate of palliative treatment was 18% (1-year overall survival rate) in chemotherapy, 33% (1-year overall survival rate) in radiotherapy, 45% and 9% in concurrent chemoradiotherapy, and 20% and 20% in sequential chemoradiotherapy, respectively. These results may suggest that palliative treatments are more effective than best supportive care. Further prospective studies are still needed to elucidate beneficial effect of palliative treatments on inoperable advanced esophageal cancer.


Microsatellite markers from Ceanothus roderickii (Rhamnaceae) using next-generation sequencing technology.
Ceanothus roderickii is an endangered shrub endemic to California. To investigate the population genetics of this species, including the genetic consequences of population fragmentation and hybridization, 10 microsatellite markers were developed. Using next-generation sequencing (454) data from a single C. roderickii individual, 10 microsatellite markers were developed. A group of 12 individuals representing all of the major C. roderickii populations were analyzed. All loci were found to be polymorphic, with a range from two to 12 alleles per locus. Observed heterozygosity ranged from 0.08 to 0.83 across loci. All 10 loci were also amplifiable in at least one other Ceanothus species. Results presented here indicate the utility of our new microsatellite primers in ongoing and future studies concerning population genetics and gene flow in C. roderickii, as well as the potential applicability of these primers in similar studies on other Ceanothus species.


A kinematic-geometric model based on ankles' depth trajectory in frontal plane for gait analysis using a single RGB-D camera.
The emergence of RGB-D cameras and the development of pose estimation algorithms offer opportunities in biomechanics. However, some challenges still remain when using them for gait analysis, including noise which leads to misidentification of gait events and inaccuracy. Therefore, we present a novel kinematic-geometric model for spatio-temporal gait analysis, based on ankles' trajectory in the frontal plane and distance-to-camera data (depth). Our approach consists of three main steps: identification of the gait pattern and modeling via parameterized curves, development of a fitting algorithm, and computation of locomotive indices. The proposed fitting algorithm applies on both ankles' depth data simultaneously, by minimizing through numerical optimization some geometric and biomechanical error functions. For validation, 15 subjects were asked to walk inside the walkway of the OptoGait, while the OptoGait and an RGB-D camera (Microsoft Azure Kinect) were both recording. Then, the spatio-temporal parameters of both feet were computed using the OptoGait and the proposed model. Validation results show that the proposed model yields good to excellent absolute statistical agreement (0.86 ≤ Rc ≤ 0.99). Our kinematic-geometric model offers several benefits: (1) It relies only on the ankles' depth trajectory both for gait events extraction and spatio-temporal parameters' calculation; (2) it is usable with any kind of RGB-D camera or even with 3D marker-based motion analysis systems in absence of toes' and heels' markers; and (3) it enables improving the results by denoising and smoothing the ankles' depth trajectory. Hence, the proposed kinematic-geometric model facilitates the development of portable markerless systems for accurate gait analysis.


Integrating segmentation methods from the Insight Toolkit into a visualization application.
The Insight Toolkit (ITK) initiative from the National Library of Medicine has provided a suite of state-of-the-art segmentation and registration algorithms ideally suited to volume visualization and analysis. A volume visualization application that effectively utilizes these algorithms provides many benefits: it allows access to ITK functionality for non-programmers, it creates a vehicle for sharing and comparing segmentation techniques, and it serves as a visual debugger for algorithm developers. This paper describes the integration of image processing functionalities provided by the ITK into VolView, a visualization application for high performance volume rendering. A free version of this visualization application is publicly available and is available in the online version of this paper. The process for developing ITK plugins for VolView according to the publicly available API is described in detail, and an application of ITK VolView plugins to the segmentation of Abdominal Aortic Aneurysms (AAAs) is presented. The source code of the ITK plugins is also publicly available and it is included in the online version.


Control of gene expression by translational recoding.
Like all rules, even the genetic code has exceptions: these are generically classified as "translational recoding." Almost every conceivable mode of recoding has been documented, including signals that redefine translational reading frame and codon assignation. While first described in viruses, it is becoming clear that sequences that program elongating ribosomes to shift translational reading frame are widely used by organisms in all domains of life, thus expanding both the coding capacity of genomes and the modes through which gene expression can be regulated at the posttranscriptional level. Instances of programmed ribosomal frameshifting and stop codon reassignment are opening up new avenues for treatment of numerous inborn errors of metabolism. The implications of these findings on human health are only beginning to emerge.


Photosynthetic capacity in relation to leaf position in desert versus old-field annuals.
Desert annuals of Death Valley, California have higher average light-saturated photosynthetic capacities and leaf nitrogen contents than do early-successional annuals of Illinois. The leaves of annuals in the light-unlimited Death Valley environment change little in specific weight, nitrogen, or photosynthetic capacity with age. In contrast, these properties decrease markedly with age in the leaves of the Illinois annuals even in leaves not exposed to the usual shading that accompanies canopy development. These results are interpreted in a carbon-gained-per-nitrogen-invested context.


The evolution of commercialized glucose sensors in China.
The glucose monitor with a screen-printed carbon sensor has been in commercial production since 1994. In last 15 years, around 10 companies have been involved in manufacturing and marketing the meters and glucose test strips and are being strong competitors of the companies which import these products. Comparison of early stage glucose meters and glucose test strips with latest fabrications showed a large increase in production volume and improved functional features. It also showed technological development of glucose monitors including circuit improvement, as more integrated computer processor units (CPU) are now being used. The technology of mass-production of disposable screen-printed test strips has been widely used in local industries mainly for the production of blood glucose test strips. The opportunities and challenges in local diabetes market are discussed in this paper.


Public health agencies outreach through Instagram during the COVID-19 pandemic: Crisis and Emergency Risk Communication perspective.
Governmental and non-governmental institutions increasingly use social media as a strategic tool for public outreach. Global spread, promptness, and dialogic potentials make these platforms ideal for public health monitoring and emergency communication in crises such as COVID-19. Drawing on the Crisis and Emergency Risk Communication framework, we sought to examine how leading health organizations use Instagram for communicating and engaging during the COVID-19 pandemic. We manually retrieved Instagram posts together with relevant metadata of four health organizations (WHO, CDC, IFRC, and NHS) shared between January 1, 2020, and April 30, 2020. Two coders manually coded the analytical sample of 269 posts related to COVID-19 on dimensions including content theme, gender depiction, person portrayal, and image type. We further analyzed engagement indices associated with the coded dimensions. The CDC and WHO were the most active of all the assessed organizations with respect to the number of posts, reach, and engagement indices. Most of the posts were about personal preventive measures and mitigation, general advisory and vigilance, and showing gratitude and resilience. An overwhelming level of engagement was observed for posts representing celebrity, clarification, and infographics. Instagram can be an effective tool for health organizations to convey their messages during crisis communication, notably through celebrity involvement, clarification posts, and the use of infographics. There is much opportunity to strengthen the role of health organizations in countering misinformation on social media by providing accurate information, directing users to credible sources, and serving as a fact-check for false information.


Algorithm-Based Liquid Formulation Development Including a DoE Concept Predicts Long-Term Viral Vector Stability.
Specifically tailored amino acid-based formulations were previously shown to have a high potential to avoid stress-mediated degradation of complex molecules such as monoclonal antibodies and viral vectors. By using adenovirus 5 (Ad5) as a model, we studied whether such formulations may also efficiently protect viral vectors in thermal stress experiments and during long-term liquid storage. Algorithm-based amino acid preselection using an excipient database and subsequent application of design of experiments (DoE) in combination with a 37°C challenging model enabled the prediction of long-term storage stability of Ad5. By statistical analysis of the Ad5 infectivity, amino acids with significant influence on Ad5 stability were detected after 2 and 3 weeks of liquid storage at 37°C. Ad5 formulations comprising positively selected amino acids did not reveal any loss of infectivity after 24 months in liquid storage at 5°C. By contrast, a 2 log reduction after 3 months and complete loss of infectivity after 18 months was observed with a standard viral vector formulation. By an optimization round, we designed a simple and well-balanced formulation avoiding MgCl2, previously considered essential in Ad5 formulations. This work demonstrates the efficacy of an algorithm-based development approach in the formulation development for viral vectors.


Central nervous system mechanisms linking the consumption of palatable high-fat diets to the defense of greater adiposity.
The central nervous system (CNS) plays key role in the homeostatic regulation of body weight. Satiation and adiposity signals, providing acute and chronic information about available fuel, are produced in the periphery and act in the brain to influence energy intake and expenditure, resulting in the maintenance of stable adiposity. Diet-induced obesity (DIO) does not result from a failure of these central homeostatic circuits. Rather, the threshold for defended adiposity is increased in environments providing ubiquitous access to palatable, high-fat foods, making it difficult to achieve and maintain weight loss. Consequently, mechanisms by which nutritional environments interact with central homeostatic circuits to influence the threshold for defended adiposity represent critical targets for therapeutic intervention.


Experimental infusion phlebitis: importance of titratable acidity on phlebitic potential of infusion solution.
The titratable acidity of infusion solutions has never been taken into account in infusion phlebitis. This study aims to clarify the importance of titratable acidity on the phlebitic potential of infusion solutions. Solutions with different titratable acidity (from 0.16 to 12 mEq/L) were infused into the ear veins of 6 rabbits for 6 h at 10 mL/kg/h, and the veins were later examined histopathologically. Even at pH 4.0, a commercial 10% glucose solution scarcely caused any changes because of its very low titratable acidity (0.16 mEq/L). A 10% glucose solution with its titratable acidity adjusted to 3 mEq/L (pH 4.3) with citrate and NaOH, however, caused phlebitic changes in all 6 rabbits, and adjusting the titratable acidity to 12 mEq/L (pH 4.4) increased the degree of phlebitis. On the other hand, a 10% glucose solution with a pH of 5.4 and a titratable acidity of 6 mEq/L caused slight phlebitic changes in half the rabbits. These results suggest that 1) the titratable acidity of infusion solutions is important to the phlebitic potential when the pH is low, 2) when the pHs are similar, the phlebitic potential of infusion solutions depend on the titratable acidity, and 3) the phlebitic potential of infusion solutions can not be estimated by pH or titratable acidity alone.


Factors associated with advanced colorectal cancer differ between young and older adults in England: a population-based cohort study.
Advanced stage presentation of colorectal cancer is associated with poorer survival outcomes, particularly among young adults. This study aimed to determine whether demographic risk factors for advanced stage presentation differed between young and older adults. Individual-level data on all incident colorectal cancers in people aged 20 years and above were extracted from the National Cancer Registration and Analysis Service database for the years 2012 to 2015. Patients were divided into two cohorts: young-onset colorectal cancer (YOCC) if aged 20-49 years and older-onset colorectal cancer (OOCC) if aged 50 years and above. Logistic regression was used to identify risk factors for advanced stage presentation, defined as TNM Stage III or IV, in each cohort. There were 7075 (5.2%) patients in the YOCC cohort and 128 345 (94.8%) patients in the OOCC cohort. Tumours in the YOCC cohort were more likely to be at an advanced stage (67.2% vs 55.3%, P < 0.001) and located distally (63.7% vs 55.4%, P < 0.001). No demographic factor was consistently associated with advanced stage presentation in the YOCC cohort. Among the OOCC cohort, increased social deprivation [OR (Index of Multiple Deprivation quintile 5 vs 1) = 1.11 (95% CI 1.07-1.16), P < 0.001], Black/Black British ethnicity [OR (baseline White) = 1.25 (95% CI 1.11-1.40), P < 0.001] and residence in the East Midlands [OR (baseline London) = 1.11 (95% CI 1.04-1.17), P = 0.001] were associated with advanced stage presentation. Demographic factors associated with advanced disease were influenced by age. The effects of social deprivation and ethnicity were only observed in older adults and mirror trends in screening uptake. Targeted interventions for high-risk groups are warranted.


Peripheral odontogenic fibroma in a Taiwan chinese population: a retrospective analysis.
A retrospective analysis of 25 cases of peripheral odontogenic fibroma (World Health Organization type) (PODF [WHO-type]) in a Taiwan Chinese population was performed at a single institution. The clinical findings, which included a wide age distribution, a female preponderance and no racial predilection, were consistent with those of previous case series reports; however, a slight preference for location in the maxilla was found in the current case series. It is noteworthy that one particularly sizable lesion was identified in a 30-year-old Chinese female who presented with a swollen mass in the right mandible that had been present for about 2 years. Intraoral examination revealed an exophytic firm mass that measured 4.5 x 4 cm, located over the right mandibular edentulous ridge from the second premolar to the second molar area. Both panoramic radiography and computerized tomography revealed multiple radiopacities within the tumor. In conclusion, the analysis of clinical data in the current case series of PODFs (WHO-type) occurring in Taiwan Chinese mostly corroborates other reports; however, an unusually large mandible lesion was noted, indicative of the apparent size that such tumors can reach unless they are surgically removed at an early stage.


Epithelial cell plasticity defines heterogeneity in lung cancer.
Lung cancer is the leading cause of cancer death for both men and women and accounts for almost 18.4% of all deaths due to cancer worldwide, with the global incidence increasing by approximately 0.5% per year. Lung cancer is regarded as a devastating type of cancer owing to its high prevalence, reduction in the health-related quality of life, frequently delayed diagnosis, low response rate, high toxicity, and resistance to available therapeutic options. The highly heterogeneous nature of this cancer with a proximal-to-distal distribution throughout the respiratory tract dramatically affects its diagnostic and therapeutic management. The diverse composition and plasticity of lung epithelial cells across the respiratory tract are regarded as significant factors underlying lung cancer heterogeneity. Therefore, definitions of the cells of origin for different types of lung cancer are urgently needed to understand lung cancer biology and to achieve early diagnosis and develop cell-targeted therapies. In the present review, we will discuss the current understanding of the cellular and molecular alterations in distinct lung epithelial cells that result in each type of lung cancer.


Increased Patient's Risk Associated with the Canadian Bioequivalence Guidance Due to Outlier Removal.
The Canadian guideline on bioequivalence allows identification of outliers through for example studentized residuals, and it explicitly accepts exclusion of subject data when their studentized residuals reach a certain magnitude. The guideline also requires that the type I errors (patient's risk, chance of declaring bioequivalence for a bioinequivalent product) be maintained at the 5% level. This manuscript investigates if the outlier removal procedure increases type I errors when alpha of 5% is used for construction of the confidence interval. Numerical simulation is used. Patient's risk may be inflated beyond 5% when the traditional 90% confidence interval is constructed. Maximum type I errors observed here are slightly above 7%. To circumvent the issue sponsors can either to abstain from outlier removal or find ways to adjust alpha levels downwards if the patient's risk is to be preserved at the 5% level. This manuscript is the first to create awareness of a potential inflation of the type I error when 90% confidence intervals are constructed as per Canadian guidance. The issue may not just affect patients in Canada but could also affect patients in the USA since the current rules allow American patients to import a 3 month supply of drugs for personal use and because the central administration is actively pursuing plans to "(…) facilitate the importation of certain prescription drugs that are approved in Canada".


[Clinical value of ammonia determination in venous blood in chronic cor pulmonale].
The authors have examined 43 workers of the Warszawa works: 20 healthy persons and 23 with chronic pulmocardiac syndrome. An increased ammonia level in venous blood, above 48 gamma %, was found in those with chronic pulmocardiac syndrome with simultaneous circulatory insufficiency. Ammonia level in the blood of those with chronic pulmocardiac syndrome but without circulatory insufficiency was normal. These studies indicate that the increase of ammonia concentration in venous blood in chronic pulmocardiac syndrome results from disturbance in hepatic cell function, intensified during circulatory insufficiency.


Phosphatidylinositol degradation in ischemic brain specifically activated by synaptosomal enzymes.
The effect of ischemia on phosphatidylinositol (PI) degrading enzymes in brain homogenate, cytosol and synaptosomes was investigated to evaluate the involvement of cholinergic receptor in PI hydrolysis during ischemia. The activity of phospholipase C in cytosol was not changed by ischemic insult. PI degradation in synaptosomes was significantly (60%) enhanced by ischemia. Atropine and gamma-butyrolactone abolished the ischemic effect on PI degradation, suggesting that the cholinergic receptor system mediates breakdown of PI during ischemia.


Characteristics and Outcomes of 360 Consecutive COVID-19 Patients Discharged From the Emergency Department With Supplemental Oxygen.
To describe characteristics and outcomes of coronavirus disease (COVID-19) patients with new supplemental oxygen requirements discharged from a large public urban emergency department (ED) with supplemental oxygen. This observational case series describes the characteristics and outcomes of 360 consecutive COVID-19 patients with new supplemental oxygen requirements discharged from a large urban public ED between April 2020 and March 2021 with supplemental oxygen. Primary outcomes included 30-day survival and 30-day survival without unscheduled inpatient admission. Demographic and clinical data were collected through a structured chart review. Among 360 patients with COVID-19 discharged from the ED with supplemental oxygen, 30-day survival was 97.5% (95% confidence interval (CI) 95.3 to 98.9%; n=351), and 30-day survival without unscheduled admission was 81.1% (95% CI 76.7 to 85.0%; n=292). A sensitivity analysis incorporating worst-case-scenario for 12 patients without complete follow-up 30 days after index visit yields 30-day survival of 95.5% (95% CI 92.5 to 97.2%; n=343), and 30-day survival without unscheduled admission of 78.9% (95% CI 74.3 to 83.0%; n=284). Among study patients, 32.2% (n=116) had a nadir ED oxygen saturation of <90%, among these 30-day survival was 97.4% (95% CI 92.6 to 99.4%; n=113), and 30-day survival without unscheduled admission was 76.7% (95% CI 68.8 to 84.1%; n=89). COVID-19 patients with new supplemental oxygen requirements discharged from the ED had survival comparable to COVID-19 ED patients with mild exertional hypoxia treated with supplemental oxygen in other settings, and this held true when the analysis was restricted to patients with nadir ED index visit oxygen saturations <90%. Discharge of select COVID-19 patients with supplemental oxygen from the ED may provide a viable alternative to hospitalization, particularly when inpatient capacity is limited.


Intestinal absorption of bile acids in the pig. Role of distal bowel.
The role of distal bowel in intestinal recycling of total bile acids was investigated in five healthy, conscious, normally fed pigs. Total bile acids appearing in the portal blood of fistulated animals were measured when bile irrigated the whole bowel (control period) and again when it was diverted at 1 m proximal to the ileocecal valve so that enterohepatic circulation was limited to only the last meter of ileum plus large bowel. Measurements were taken just after the bile had been diverted and then four days later when a new steady state was reached. Under steady-state conditions bile acid reabsorption rate in distal bowel was 20% of the normal rate. This result has been discussed taking into account the high but transient ability of distal bowel to spare bile acids measured in the first hours after bile diversion. The present experiment, together with some other in vivo trials on small laboratory animals, indicate that the proximal bowel may take a large part in bile acid absorption and that we need to reevaluate the notion that bile acid absorption takes place mainly in distal bowel.


Longitudinal assessment of callous/impulsive traits, substance abuse, and symptoms of depression in adolescents: a latent variable approach.
Latent variable structural modeling was used to examine the associations among callous/impulsive personality traits, substance abuse, and symptoms of depression in a sample of 156 adjudicated male adolescents. Assessments were conducted at baseline and 6-month follow-up. The results highlight an unfolding of interrelationships among disturbances in personality, substance use, and mood over time.


Lactic acid-induced swelling in C6 glial cells via Na+/H+ exchange.
One of the primary consequences of ischemia is tissue acidification due to anaerobic production of lactic acid. Upon reperfusion and recovery of pH, cytotoxic edema often ensues. Na+/H+ exchange, a mechanism involved in the regulation of intracellular pH (pHi), is activated by low intracellular pH, is dependent on extracellular Na+, and is inhibited by low extracellular pH (pH less than 6) or by amiloride. In this study we explore the role of Na+/H+ exchange in cell swelling following cytoplasmic acidification of C6 glioma cells. Postischemic intracellular acidification was simulated in vitro by exposure of cells in suspension to: (1) 20 or 140 mM lactic acid; or (2) 10 microM oligomycin. pHi was monitored fluorimetrically using the intracellularly trapped pH-sensitive dye bis(carboxyethyl)carboxyfluorescein. Cell volume was measured electronically with a Coulter Counter/Channelyzer. Both simulations of ischemia caused intracellular acidification followed by recovery. pHi recovery was mediated by Na+/H+ exchange, since it was amiloride-sensitive and Na+-dependent. This pHi reversal following lactic acid-induced acidification was also inhibited at pHo less than 6. Volume measurements showed that cells suspended in 140 mM Na-lactate/lactic acid swelled by 19% over 15 min. This swelling was Na+-dependent, and inhibited by amiloride and pHo less than 6. These results suggest that Na+/H+ exchange may be involved in cell swelling following cytoplasmic acidification, and thus may be involved in postischemic cytotoxic brain edema.


Post COVID fatigue: Can we really ignore it?
Long-COVID, also referred to as post-acute COVID-19, chronic COVID-19, post-COVID syndrome, or post-acute sequelae of SARS-CoV-2 infection (PASC), generally refers to symptoms that develop during or after acute COVID-19 illness, continue for ≥12 weeks, and are not explained by an alternative diagnosis. It is not yet known whether "long-COVID" represents a new syndrome unique to COVID-19 or overlaps with recovery from similar illnesses. It's difficult for physicians to predict when symptoms will improve as it varies differently in different people. Patient's recovery depends on various factors including age, associated comorbidities, severity of COVID-19 infection. Some symptoms, like fatigue, might continue even while others improve or go away. This review addresses the pathogenesis, presentation of post covid fatigue, its severity and its management.


Laparoscopic liver resection versus percutaneous radiofrequency ablation for small hepatocellular carcinoma.
Laparoscopic liver resection (LLR) and radiofrequency ablation (RFA) play central roles to treat early-stage hepatocellular carcinoma (HCC, ≤3 cm, 1-3 nodules, and no macrovascular involvement), although data are lacking regarding whether LLR or RFA is preferable. This study aimed to compare outcomes of both treatments for small HCCs. Treatment outcomes of small HCCs were compared between all the minor LLRs performed between 2005 and 2016 and RFAs performed between 2011 and 2016 at Kyoto University. A total of 85 and 136 patients underwent LLR and RFA, respectively. Patients that underwent LLR had higher incidence of blood transfusions, complications, and longer hospital stay. Overall and disease-specific survival rates were similar between LLR and RFA; however, recurrence-free (49.2% vs. 22.1% at 3-year) and local recurrence-free survival rates (94.9% vs. 63.6% at 3-year) were higher after LLR. Multivariate analyses identified that multiple nodules and 65-year-old and above are predictors of disease-specific survival, and that RFA is a predictor of recurrence and local recurrence. RFA is less invasive, although both LLR and RFA are safe and effective. LLR provides better local control with superior recurrence-free and local-recurrence free survival. These results help optimize treatment selection based on patient-specific factors.


Characterization of two novel KRAB-domain-containing zinc finger genes, ZNF460 and ZNF461, on human chromosome 19q13.1-->q13.4.
This study reports the cloning and characterization of two novel human zinc finger protein cDNAs (ZNF460 and ZNF461) from a fetal brain cDNA library. The ZNF460 cDNA is 3,135 bp in length encoding a 562-amino-acid polypeptide and the ZNF461 cDNA is 2,548 bp encoding a 563-amino-acid protein. Both of the proteins contain a KRAB A+B box and eleven C2H2 type zinc finger motifs. ZNF461 shows high similarity with the rat GIOT-1 gene (GIOT1). The ZNF460 gene mapped to 19q13.4 with 3 exons, and ZNF461 mapped to 19q13.1 with 6 exons. Both of the two genes are ubiquitously expressed in normal human tissues and the abundance of the ZNF460 mRNA is relatively low.


Experience with OKT3 in vascularized pancreas transplantation.
With refinements in technical aspects of whole organ pancreas transplantation, allograft rejection is currently the major cause of graft failure. The monoclonal antibody OKT3 has emerged as a highly effective antirejection therapy in renal and hepatic allograft recipients, but its efficacy in pancreas transplantation remains to be determined. During a 12-month period, 28 vascularized whole organ pancreas transplants were performed with pancreatico-cystostomy. Sixteen episodes of allograft rejection were treated with monoclonal antibody OKT3. Indications for OKT3 use included steroid- or antilymphocyte globulin (ALG)-resistant allograft rejection in isolated pancreas (n = 8) or simultaneous kidney-pancreas (n = 8) transplants. A total of 34 rejection episodes occurred in the 16 patients (mean, 2.1; range, one to five). The diagnosis of rejection was based on clinical criteria, a reduction in urinary amylase clearance, radionuclide scanning, hyperglycemia, or associated renal allograft dysfunction in combined engraftments. Postoperative immunosuppression consisted of cyclosporine, prednisone, azathioprine, and prophylactic ALG. OKT3 was administered for a full 14-day course concomitant with low-dose steroids, azathioprine, and cyclosporine. The mean age of the patient population was 32.1 years (range 24 to 39) with a mean duration of insulin-dependent diabetes mellitus (IDDM) of 20.9 years. Monoclonal antibody therapy was instituted in two clinical settings: early rejection (within 3 months of transplant, n = 10); and late rejection (after 3 months, n = 6). OKT3 successfully reversed allograft rejection in ten (62.5%) cases, including six early (60%) and four late (66.7%) episodes. In isolated pancreas transplants, OKT3 therapy reversed pancreas allograft rejection in only two patients (25%).(ABSTRACT TRUNCATED AT 250 WORDS)


Mechanisms underlying gastric mucosal damage induced by indomethacin and bile-salts, and the actions of prostaglandins.
1 The mechanisms by which -he bile salt, sodium taurocholate, potentiates the formation of gastric mucosal erosions induced by indomethacin has been investigated in the rat. 2 Systemic administration of indomethacin lowered resting mucosal blood flow but had no effect on the acid back-diffusion across the mucosa. 3 Gastric perfusion of taurocholate in acid solution increased acid back-diffusion and lowered the potential differences. This was accompanied by an increase in mucosal blood flow, which may represent a protective mechanism in the mucosa. 4 Administration of indomethacin during acid-taurocholate perfusion reduced this elevated mucosal blood flow without any further change in acid back-diffusion. 5 The results suggest that although a decrease in mucosal blood flow or an increase in acid back-diffusion can lead to a low incidence of erosions, a combination of both produces extensive mucosal damage. 6 The (15S)-methyl analogue of prostaglandin E2 reduced erosion formation induced by indomethacin and acid-taurocholate administration. 7 It is suggested that this protective action of the prostaglandin analogue may be linked to changes in gastric mucosal permeability and in mucosal blood flow.


Therapeutic Efficacy and Prediction of 18F-FDG PET/CT-Assisted Botulinum Toxin Therapy in Patients With Idiopathic Cervical Dystonia.
This study aimed to investigate the therapeutic efficacy of 18F-FDG PET/CT-assisted botulinum toxin (BTX) injection therapy and predictive PET findings in relation to a good response in patients with idiopathic cervical dystonia (ICD). A total of 78 patients was enrolled from November 2007 to July 2018. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score was determined at baseline and 4 weeks after BTX injection guided by electromyography and PET/CT. The number of hypermetabolic muscles, the highest SUVmax among hypermetabolic muscles, and the total SUVmax of hypermetabolic muscles were evaluated as pretreatment PET parameters. A good response was defined as a reduction rate ≥30% and a point decrease ≥15 of the TWSTRS total score. Half of the subjects showed a good response. Good responders had significantly higher baseline TWSTRS scores than poor responders (total score, P < 0.001; severity, P < 0.001; disability, P < 0.001; pain, P = 0.026). Good responders also had significantly higher numbers of hypermetabolic muscles and BTX-injected hypermetabolic muscles (P < 0.001, both). In multivariable analysis, the baseline TWSTRS disability subscale score and the number of BTX-injected hypermetabolic muscles were significant predictors for good response (P = 0.001 and P = 0.028). The aforementioned 3 PET parameters were positively correlated with the baseline TWSTRS scores. In addition, PET/CT well detected dystonic deep cervical muscles. FDG PET/CT-assisted BTX injection therapy showed good therapeutic efficacy in ICD patients. The numbers of hypermetabolic cervical muscles and BTX-injected hypermetabolic muscles may be helpful in predicting a good response.


Proportionality at birth. Associations with weight, gestational age and sex.
501 small (SGA), 330 average (AGA) and 460 large for gestational age (LGA) babies were measured at birth. Head-chest, head-crown-rump length, and chest-crown-rump length ratios were used to evaluate the changing patterns of proportionality with increasing gestational age. The SGA group showed strong negative correlations for head-chest and head-length ratios, and positive correlations for chest-length ratios. The patterns were similar in the AGA group, only less evident. For all three measures of proportionality, correlations with gestational age in the LGA group were close to zero. In each group boys had higher head-chest ratios than girls.


Real-time measurement of solute partitioning to lipid monolayers.
The interaction of a peripheral protein with a lipid-water interface can show a pronounced dependence on the composition and two-dimensional packing density of the lipids that comprise the interface. We report a novel optical method for measuring the adsorption of macromolecules, such as proteins and nucleic acids, and smaller solutes, such as drugs, to lipid monolayers at the gas-liquid interface. Using fluorescence emission from proteins and a small molecule, we demonstrate that the emissions from these solutes when in the aqueous phase and when associated with the monolayer can be temporally separated. Such separation allows measurement of the extent of solute adsorption, spectral characterization of the adsorbed solute, and characterization of lipid organization using adsorption kinetics. The method does not require, but is compatible with, the solute having different spectral properties in the bulk and surface phases. Indeed, if optical signals from adsorbed and soluble solute are the same or their relationship is known, absolute surface excess of adsorbed solute can be calculated without independent calibration. With appropriate instrumental configuration, the method should be adaptable for screening solutes for interaction with planar monolayers having both well-defined composition and adjustable lipid packing density.