Application of the 'profiles of relationship' method to distantly related proteins.
An analysis is made of the applicability of the recently published 'profiles of relationship' method for establishing evolutionary relatedness among proteins by using the distantly related proinsulin and neurotoxin protein sequences as a test object. The method is based on a simultaneous group analysis of both the frequency of acceptance of mutations and their genetic code interchangeability. Regularities in the patterns of the profiles, which reflect decreased similarity with the passage of time, are established for typical cases of closely related, distantly related and unrelated proteins. This makes it possible to distinguish distantly related from unrelated proteins without extensive statistical randomization procedures. New evidence is stated in favour of a previously suggested definition of interchangeability which does not consider the third base in the codon. The applicability of the profiles of relationship method is examined on the distant relationship between proinsulin and the snake and scorpion neurotoxins which has been established previously by means of conventional approaches.


Sedimentary hydrocarbons and sterols in a South Atlantic estuarine/shallow continental shelf transitional environment under oil terminal and grain port influences.
Sterols and hydrocarbons were determined in the surface sediments from the transitional environment between Paranaguá Bay and the shallow continental shelf in the South Atlantic to assess the sources of organic matter (OM) and the contamination status of an area exposed to multiple anthropogenic inputs. Total aliphatic hydrocarbon concentrations were less than 10μgg(-1), which is typical of unpolluted sediments, and related to recent inputs from higher terrestrial plants. Total polycyclic aromatic hydrocarbon ranged from<DL to 14.41ngg(-1) (dry weight), which was predominantly derived from combustion with non-detectable levels occurring in 65% of the samples. Sterols typically related to marine sources predominated in the analysed sediments. Hence, the study area was protected from human activity. The relative absence of anthropogenic input and OM preservation clearly indicate that the organic markers analysed can be used to investigate the biogenic input of sedimentary OM in the study area.


Selective deficiency of hepatic triglyceride lipase and hypertriglyceridaemia in kwashiorkor.
1. Serum postheparin lipolytic activities (PHLA), triglyceride and free fatty acid concentrations were determined in children with kwashiorkor before and after treatment and also in normal control children. 2. Using the range (571-1650 mumol/l) of serum triglyceride of the control children as normal, five (20%) of the twenty-five children with kwashiorkor had low (less than 570 mumol/l), thirteen (52%) had normal (571-1650 mumol/l) and seven (28%) had high (more than 1650 mumol/l) serum triglyceride levels. 3. The serum PHLA did not show any definite correlation with the level of circulating triglycerides, although the lowest levels of PHLA were found in the malnourished children with highest triglyceride level. 4. While the hepatic PHLA in the malnourished children was significantly less than control value, the extrahepatic PHLA did not differ significantly. 5. After treatment, serum PHLA rose significantly and the mean levels were within normal range. 6. Our findings suggest that a defect in catabolism of very-low-density lipoprotein caused by a low hepatic PHLA may cause hypertriglyceridaemia in children with kwashiorkor.


Bioavailability of generic 0.05% difluprednate emulsion in the aqueous humor, cornea, and conjunctiva of New Zealand rabbits after a single dose compared with commercial difluprednate.
To determine the concentration after a single dose of generic 0.05% difluprednate and commercial difluprednate in the aqueous humor, cornea, and conjunctiva of New Zealand rabbits, a preclinical study in 72 male New Zealand white rabbits was performed. A single dose (50 μL) of two 0.05% difluprednate ophthalmic formulations was instilled in both eyes. Conjunctiva, cornea, and aqueous humor samples were collected at nine time points over 8 h (four animals per time point). The active metabolite of difluprednate, 17-difluoroprednisolone-butyrate (DFB), concentrations was quantified using HPLC. Measurable levels of DFB were quantified in all three ocular tissues. After a single instillation, the highest concentration of difluprednate was found between 30 and 60 min in the conjunctiva, cornea, and aqueous humor, respectively. There was no significant difference between both formulations in any tissue at any time point. After 3 h, no metabolites of either emulsion were found in any tissue. Difluprednate penetrates into different ocular tissues. Generic difluprednate has a similar pharmacokinetic profile compared with commercial difluprednate.


Cannabis and alcohol use, affect and impulsivity in psychiatric out-patients' daily lives.
Cannabis and alcohol are the most commonly used (il)licit drugs world-wide. We compared the effects of cannabis and alcohol use on within-person changes in impulsivity, hostility and positive affect at the momentary and daily levels, as they occurred in daily life. Observational study involving ecological momentary assessments collected via electronic diaries six random times a day for 28 consecutive days. Out-patients' everyday life contexts in Columbia, MO, USA. Ninety-three adult psychiatric out-patients (85% female; mean = 30.9 years old) with borderline personality or depressive disorders, who reported using only cannabis (n = 3), only alcohol (n = 58) or both (n = 32) at least once during the study period. Real-time, standard self-report measures of impulsivity, hostility and positive affect, as impacted by momentary reports of cannabis and alcohol use. Cannabis use was associated with elevated feelings of impulsivity at the day level [b = 0.83, 95% confidence interval (CI) = 0.17-1.49] and increased hostility at the momentary (b = 0.07, 95% CI = 0.01-0.12) and person (b = 0.81, 95% CI = 0.15-1.47) level. Alcohol use was associated with elevated feelings of impulsivity at the momentary (b = 0.42, 95% CI = 0.13-0.71) and day levels (b = 0.82, 95% CI = 0.22-1.41) and increased positive affect at the momentary (b = 0.12, 95% CI = 0.06-0.18) and day (b = 0.33, 95% CI = 0.16-0.49) levels. Cannabis and alcohol use are associated with increases in impulsivity (both), hostility (cannabis) and positive affect (alcohol) in daily life, and these effects are part of separate processes that operate on different time-scales (i.e. momentary versus daily).


Bifid root and root canal in mandibular second premolar and its management--a case report.
Morphogically the mandibular second premolars present one root canal (97.5%). So far only a small percentage (2.5%) of cases were reported to have two root canals where they present the canals on the buccal and lingual direction of the root. Here an unusual case of two root canals, which are situated in mesial and distal direction is presented.


Alternating gender incongruity: a new neuropsychiatric syndrome providing insight into the dynamic plasticity of brain-sex.
Between the two extreme ends of human sexuality - male and female - lie a poorly understood and poorly studied spectrum of ambiguously defined sexual identities that are very much a part of the human condition but defy rigid classification. "Bigender" is a recently formed sub-category of transgenderism, describing individuals who experience a blending or alternation of gender states. While recognized nominally by the APA, no scientific work to our knowledge has addressed this fascinating condition, or proposed any physiological basis for it. In addition, the alternation aspect has not been proposed as a nosological entity distinct from blending. We present descriptive data suggesting that many bigender individuals experience an involuntary switching of gender states without any amnesia for either state. In addition, similar to transsexual individuals, the majority of bigender individuals experience phantom breasts or genitalia corresponding to the non-biologic gender when they are in a trans-gender state. Finally, our survey found decreased lateralization of handedness in the bigender community. These observations suggest a biologic basis of bigenderism and lead us to propose a novel gender condition, "alternating gender incongruity" (AGI). We hypothesize that AGI may be related to an unusual degree or depth of hemispheric switching and corresponding callosal suppression of sex appropriate body maps in parietal cortex- possibly the superior parietal lobule- and its reciprocal connections with the insula and hypothalamus. This is based on two lines of reasoning. First, bigender individuals in our survey sample reported an elevated rate of bipolar disorder, which has been linked to slowed hemispheric switching. We hypothesize that tracking the nasal cycle, rate of binocular rivalry, and other markers of hemispheric switching will reveal a physiological basis for AGI individuals' subjective reports of gender switches. Switching may also trigger hormonal cascades, which we are currently exploring. Second, we base our hypotheses on ancient and modern associations between the left and right hemispheres and the male and female genders. By providing a case of sharp brain-sex shifts within individuals, we believe that the study of AGI could prove illuminating to scientific understanding of gender, body representation, and the nature of self.


Fish liver oil and propolis as protective natural products against the effect of the anti-epileptic drug valproate on immunological markers of bone formation in rats.
Epilepsy is a major public health problem affecting nearly 50 million people world wide. Treatment with anti-epileptic drugs (AEDs) is generally chronic if not life long and may be associated with significant metabolic effects including decreased bone mass and increased fractures. The aim of this work was to investigate the protective role of fish liver oil and propolis against the effect of the drug valproate that is widely used for treatment of epilepsy. Group of 40 rats was divided into four groups each contain 10 rats. The first group (group I) is healthy normal rats, as control. Epilepsy was conducted in the rest of the rats. The epileptic rats were divided into three subgroups: group II was epileptic group, supplemented orally with valproate. The third group was epileptic group which supplemented orally with valproate in concomitant with fish liver oil, the last group; group IV was epileptic group which supplemented orally with valproate in concomitant with propolis. In the present study oral administration of valproate to the epileptic rats by a dose of 400mg/kg/daily for six months (group II) resulted in a significant increase of bone alkaline phosphatase, osteocalcin and N-telepeptide of type 1 collagen (NTX) relative to the control group. There were increase of receptor activator of NF kappa B ligand (RANKL), tumor necrosis factor - alpha (TNF-alpha) and decrease of osteoprotegrin (OPG) compared to normal control. Administration of fish liver oil orally in a dose of 0.4mg/kg daily in concomitant with valproate 400mg/kg daily for six months (group III), result in reduction of N-telepeptide of type 1 collagen (NTX) in comparison to group II and with no significant increase than the control (group I). There were high significant increase of bone alkaline phosphatase and osteocalcin compared to control group I. There was high significant increase of bone alkaline phosphatase than group II and increase in osteocalcin, and decrease in N-telepeptide of type 1 collagen (NTX) compared to group II. A significant increase in osteoprotegrin (OPG) in comparison to group II and to control (group I) with a decrease in RANKL compared to group II and with no significant increase than normal control (group I). The TNF-alpha showed a significant decrease compared to group II with no significant increase than normal control. Administration of propolis orally in a dose of 50mg/kg daily in combination with valproate 400mg/kg/daily for six months (group IV) cause increase in bone alkaline phosphatase with no statistical difference between osteocalcin and N-telepeptide of type 1 collagen (NTX) and normal control (group I). There were increase in bone alkaline phosphatase than group II but less than group III. The increase in osteocalcin in-group III (fish oil group) was significantly higher than in-group IV and there was no statistical difference between it and group II. Where the N-telepeptide of type 1 collagen (NTX) the bone resorption marker was significantly higher than Group III and significantly lower than group II. There was a decrease of RANKL in comparison to group II with no significant difference than group III and a significant increase than control group. There was an increase in osteoprotegrin (OPG) in comparison to control (group I), group II and from group III. There was decrease in TNF-alpha than group III, group I and group II. In conclusion, in epileptic rats treated with valproate (which cause osteoporosis) fish liver oil and propolis increase the bone formation markers and decrease the bone resorption one's. They increase the OPG and decrease TNF-alpha, and RANKL which inhibit the osteoclastogenesis. We recommend the use of Fish Oil, or propolis as a prophylactic treatment for epileptic patients using valproate against the side effect of valproate on bone.


Posterior sagittal approach for treatment of presacral masses in infancy.
There are very few reports on the surgical management of presacral masses (PSM) via a posterior sagittal (PS) approach. Between 1994 and 2000, we followed five girls who had been operated upon for PSMs via a PS approach. The mean age was 28.8 +/- 16.6 months (6-48 months). The mean follow-up was 3 +/- 1.6 years (1-5 years). Although two patients had yolk-sac tumors, all patients are still alive. We believe that this is a safe and satisfactory method for resection of PSMs.


Evidence of higher ethynylestradiol blood levels in human hypertensive oral contraceptive users.
These studies were designed to investigate the differences in blood plasma levels of ethynylestradiol (EE2) in women who developed hypertension while taking combined estrogen and progesterone oral contraceptives (OCs) and in normotensive OC users. Blood samples were collected in heparinized tubes 10 hours after OC ingestion, the plasma was separated, and EE2 was measured by radioimmunoassay. The results showed significantly higher plasma levels of EE2 in the hypertensive OC users as compared with the levels in normotensive OC users (P less than 0.01). In another study, blood samples from hypertensive and normotensive OC users were obtained for 3 consecutive days at fixed intervals following OC ingestion, and plasma levels of EE2 were measured. The results showed consistently higher EE2 blood levels during this 3-day period in the hypertensive subjects (P less than 0.01). It is postulated that the higher blood levels of EE2 in hypertensive OC users result from either decreased metabolism or excretion of synthetic estrogens.


Vaginal wall fibroid.
Localization of leiomyomas in the vaginal wall is very rare. We report about a case of a vaginal leiomyoma in the anterior vaginal wall, preoperatively identified with sonography and CT. Surgical enucleation was performed. Surgical removal in these cases is safe and usually with minimal bleeding.


In vitro efficacy of several antimicrobial combinations against Brucella canis and Brucella melitensis strains isolated from dogs.
In vitro efficacy of tetracyclines, aminoglycosides, fluoroquinolones, rifampin and macrolides and their combinations against four Brucella canis and two B. melitensis strains isolated from dogs was evaluated by means of inhibition tests: minimal inhibitory concentration (MIC) and fractional inhibitory concentrations (FIC) and by bactericidal tests: minimal bactericidal concentrations (MBC) and kill-time experiments. In inhibition studies, tetracyclines showed the lowest MICs of all compounds tested (0.06-0.50 mg/l). However, doxycycline did not inhibit growth of B. canis D-519 strain at concentrations lesser than 1 mg/l. Most strains were resistant to macrolides. Chequerboard MIC titrations showed synergy between enrofloxacin and aminoglycosides against B. canis RM 6/66 reference strain and between doxycycline and streptomycin against B. canis D-519 strain. Combinations of tetracyclines and aminoglycosides were at the limit of synergy for B. canis RM 6/66 strain (FIC = 0.56). Combination of doxycycline and rifampin seemed to be antagonistic against B. canis M-strain (FIC = 3). Other combinations studied were indifferent or additive against all other strains. In bactericidal studies, aminoglycosides, fluoroquinolones and rifampin showed bactericidal activity at 1-4 x MIC but tetracyclines or macrolides did not kill brucellae below 8 x MIC. Results of kill-time experiments indicated that streptomycin was the antimicrobial agent tested which more rapid killed brucellae. In most cases, doxycycline did not kill brucellae in 96 h of incubation. Which using rifampin alone, some inocula of B. canis strains RM 6/66, D-519 and M- showed regrowth after 24 h of incubation. Retesting of these regrowing brucellae showed an increased MIC indicating development of phenotypic resistance. Testing of antimicrobial combinations in kill-time experiments indicated synergy between enrofloxacin and streptomycin and antagonism between rifampin and doxycycline both for B. canis RM 6/66 strain.


A report of a retained bullet in the bladder which migrated from an extraperitoneal injury.
Genitourinary trauma secondary to a gunshot wound is uncommon as it only occurs in about 10% of cases. We present a case of a gentleman who suffered a gunshot wound to the pelvis. The bullet was originally extraluminal to the bladder; however, upon repeat CT scan eight days later, the bullet had migrated intra-luminally. We hope to show through this case that uncomplicated extraperitoneal injuries with an adjacent missile might benefit from early surgical exploration.


Ets protein Elf-1 bidirectionally suppresses transcriptional activities of the tumor suppressor Tsc2 gene and the repair-related Nth1 gene.
Alterations in the rat tuberous sclerosis gene (Tsc2) cause renal cell carcinomas (RCCs) with complete penetrance. In this study, it was shown that the minimal core promoters of the rat Tsc2 and endonuclease III 1 (Nth1) genes, lying in a 5'-to-5' arrangement, were localized in a 0.11-kb region containing two Ets binding sites (EBSs). This region worked as a bidirectional promoter in a single reporter plasmid. Mutational inactivation of each of the two EBSs significantly reduced promoter activity. Moreover, gel shift assays revealed the presence of specific EBSs-protein complexes. These results demonstrate that some members of the Ets family positively regulate the promoter activities of the Tsc2/Nth1 genes by binding to the EBSs. We identified Elf-1 as a binding factor for EBSs through super-shift assays, and detected approximately 35 kDa bands with an EBSs-containing DNA probe by Southwestern blot analysis. Forced expression of Elf-1 in cells, however, bidirectionally suppressed the activities of the Tsc2/Nth1 promoters. Elf-1 may be a negative regulator of Tsc2/Nth1 gene expression and may compete against positive regulators for binding to the EBSs. Our observations suggest that mechanisms that inactivate Tsc2 gene expression, such as promoter suppression, may exist.


HAWK and HARRIER: Ninety-Six-Week Outcomes from the Phase 3 Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration.
To report the 96-week outcomes from HAWK and HARRIER. Phase 3, prospective, randomized, double-masked, multicenter studies comparing efficacy and safety of brolucizumab 3 mg (HAWK only) and 6 mg with aflibercept 2 mg in eyes with neovascular age-related macular degeneration (nAMD). Treatment-naïve eyes with nAMD were randomized 1:1:1 to brolucizumab 3 mg (n = 358), brolucizumab 6 mg (n = 360), aflibercept 2 mg (n = 360; HAWK) or 1:1 to brolucizumab 6 mg (n = 370), aflibercept 2 mg (n = 369; HARRIER). After 3 monthly loading doses, brolucizumab patients received every (q)-12-week (w) dosing, possibly adjusting to q8w dosing if disease activity was present at predefined disease activity assessment (DAA) visits. Aflibercept was dosed in a fixed q8w regimen. Visual and anatomic parameters were assessed throughout. Primary end point was at week 48 (48w), confirmed at 96w. Mean best-corrected visual acuity (BCVA) change from baseline, proportion of patients on an q12w regimen, retinal thickness, retinal fluid changes, and safety, all to 96w. Mean change (least squares [LS] mean ± standard error) in BCVA from baseline to 96w in HAWK was 5.6±0.79 Early Treatment Diabetic Retinopathy Study (ETDRS) letters for brolucizumab 3 mg, 5.90±0.78 letters for brolucizumab 6 mg, and 5.3±0.78 letters for aflibercept and in HARRIER was 6.1±0.73 letters for brolucizumab 6 mg and 6.6 ± 0.73 letters for aflibercept. Greater central subfield thickness reductions were observed with brolucizumab 6 mg versus aflibercept in HAWK (LS mean, -174.8 μm vs. -148.7 μm; 95% confidence interval for treatment difference, -46.2 to -5.9 μm; P = 0.0115) and HARRIER (LS mean, -197.7 μm vs. -155.1 μm; 95% confidence interval for treatment difference, -62.0 to -23.3 μm; P < 0.0001). The proportions of eyes with intraretinal fluid and/or subretinal fluid (IRF/SRF) at 96w in HAWK were 31% (P = 0.0688) and 24% (P = 0.0002) for brolucizumab 3 mg and 6 mg and 37% for aflibercept, whereas in HARRIER, they were 24% for brolucizumab 6 mg (P < 0.0001) and 39% for aflibercept. At 92w (last DAA), a 45.4% and 38.6% probability was observed for brolucizumab 6 mg patients of maintaining an q12w treatment regimen in HAWK and HARRIER, respectively. Brolucizumab exhibited an overall well-tolerated safety profile. Visual outcomes from 48w to 96w confirm the efficacy achieved at 48w. Brolucizumab demonstrated greater fluid resolution compared with aflibercept. The q12w potential for brolucizumab observed at 48w was maintained to 96w.


Folkbiology meets microbiology: a study of conceptual and behavioral change.
Health education can offer a valuable window onto conceptual and behavioral change. In Study 1, we mapped out 3rd-grade Chinese children's beliefs about causes of colds and flu and ways they can be prevented. We also explored older adults' beliefs as a possible source of the children's ideas. In Study 2, we gave 3rd- and 4th-grade Chinese children either a conventional cold/flu education program or an experimental "Think Biology" program that focused on a biological causal mechanism for cold/flu transmission. The "Think Biology" program led children to reason about cold/flu causation and prevention more scientifically than the conventional program, and their reasoning abilities dovetailed with their mastery of the causal mechanism. Study 3, a modified replication of Study 2, found useful behavioral change as well as conceptual change among children who received the "Think Biology" program and documented coherence among knowledge enrichment, conceptual change, and behavioral change.


Cell growth and protein formation on various microcarriers.
A large number of microcarriers are commercially available. The capability of cells to successfully proliferate on microcarriers varies with cell lines and media. Choosing the right microcarrier for a particular cell line is more than a choice of a microcarrier. It is part of an integrated process design. A detailed picture of cell growth and product formation will not only be essential in identifying the kind of microcarrier, but also in determining other parts of the process, such as operation mode and media. Our initial screening on thirteen microcarriers showed that cultures on some microcarriers reached a low cell density but high cell-specific productivity, and high density microcarrier cultures have a low specific productivity. The result is a similar product output per unit volume and time for these two types of cultures. An ideal culture system shall have increased volumetric productivity at elevated cell density. This requires the process goal to be incorporated as early as cell line construction and screening. A high output process can then be realized through high density culture.


Abolishment of 24-hour continuous medical call duty in quebec: a quality of life survey of general surgical residents following implementation of the new work-hour restrictions.
The implementation of work hour restrictions across North America have resulted in decreased levels of self injury and medical errors for Residents. An arbitration ruling in Quebec has led to further curtailment of work hours beyond that proposed by the ACGME. This may threaten Resident quality of life and in turn decrease the educational quality of surgical residency training. We administered a quality of life questionnaire with an integrated education quality assessment tool to all General Surgery residents training at McGill 6 months after the work hour restrictions. Across several strata respondents reveal a decreased sense of educational quality and quality of life. The arbitration argued that work- hour restrictions would be necessary to improve quality of life for trainees and hence improve patient safety. Results from this study demonstrate the exact opposite in a large majority of respondents, who report a poorer quality of life and a self-reported inability on their part to provide continuous and safe patient care.


Postoperative falls in the acute hospital setting: characteristics, risk factors, and outcomes in males.
Hospital falls are an important cause of morbidity in older surgical patients. The objectives of this study were to describe the characteristics, risk factors, and outcomes for postoperative falls. A retrospective study was performed on patients who were admitted to the hospital for more than 23 hours after surgery. Patients who fell within 30 days of their surgery were considered to have experienced a postoperative fall. Over 5 years and 9,625 inpatient surgical procedures, 154 patients experienced 190 falls. Injuries resulting from postoperative falls included major injury (hip fracture), less than 1%; injury requiring intervention, 2%; injury not requiring intervention, 27%; and no injury, 70%. Variables associated with postoperative falls included older age, functional dependence, lower albumin level, and higher American Society of Anesthesia score. One or more postoperative falls occurred in 1.6% of surgical inpatients and can lead to significant morbidity. Recognition of fall risk factors will help design postoperative fall prevention programs by identifying patients at highest risk for postoperative falls.


Peripheral neural sheath tumors (PNST)--what a radiologist should know.
Peripheral neural sheath tumors (PNST) are rare and the common goal of management focuses on eliminating pain and maximizing function of the affected nerve. Therefore preoperative assessment of the specific morphological behaviour of such tumors regarding the nerves internal architecture is of utmost importance. PNSTs may affect one or more fascicles of a peripheral nerve resulting in a significant functional loss after resection and the necessity of functional reconstruction in one step. Enhancement of preoperative information should also address the biological behaviour of the tumor regarding its dignity and the resulting implications on amount of radical resection, additional treatment and prognosis. Since high-resolution techniques promise more and more detail resolution in many fields of imaging, delineation of intra- and extraneural processes as well as biological informations shall lead towards a well prepared and foreseeable image-guided treatment of PNSTs.


Müllerian adenosarcoma of vagina arising in persistent endometriosis: report of a case and review of the literature.
Primary adenosarcoma arising in vaginal endometriosis poses a diagnostic challenge, especially in superficial vaginal biopsies. A 56-year-old woman, with a prior diagnosis of ovarian endometriosis, presented with a rapidly enlarging mass of the vaginal vault. Two prior biopsies were benign and showed endometriosis. The third vaginal biopsy revealed benign endometriotic glands cuffed by a cellular stroma with moderate cytologic atypia, a histological appearance diagnostic of Müllerian adenosarcoma. A 16-cm vaginal mass that had infiltrated the pelvic structures was resected. Close clinical follow-up of extrauterine endometriosis and clinical-pathologic correlation is necessary. Histological features such as cellular stromal cuffing around benign endometriotic glands are critical in arriving at a timely diagnosis of adenosarcoma in patients with persistent extrauterine endometriosis, even in superficial vaginal biopsies.


Acetabular Anteversion Changes Due to Spinal Deformity Correction: Bridging the Gap Between Hip and Spine Surgeons.
Hip osteoarthritis often coexists with adult spinal deformity, an abnormality in which sagittal spinopelvic malalignment is present. Debate exists whether to perform spinal realignment correction or total hip arthroplasty first. Hip extension and pelvic tilt are important compensatory mechanisms in the setting of sagittal spinopelvic malalignment and change after spinal realignment. We performed this study to evaluate the effect that the spinal realignment surgical procedure has on acetabular anteversion. This study is a retrospective review of a multicenter, prospective, consecutive database of patients with adult spinal deformity who underwent surgical spinal realignment. Only patients who already had undergone a total hip arthroplasty prior to the spinal realignment procedure were retained for analysis. Patients were excluded if they had insufficient imaging or large-head, metal-on-metal bearings or they had undergone revision total hip arthroplasty in the study period. Acetabular anteversion was calculated via the ellipse method on a standing, posterior-anterior, 90-cm radiograph with a well-centered pelvis. Anteversion was measured preoperatively and at six weeks or three months after the spinal realignment procedure. Spinopelvic parameters measured included pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, T1 pelvic angle, sagittal vertical axis, T1-spinopelvic inclination, and thoracic kyphosis. Forty-one hips (thirty-three patients) were identified. Acetabular anteversion significantly reduced (p < 0.001) after spinal correction by mean change of -4.96° (range, -22.32° to +2.36°). The change in anteversion correlated with the changes in sagittal pelvic orientation (0.828 for the pelvic tilt, -0.757 for the sacral slope, and -0.691 for the lumbar lordosis) and global spinopelvic alignment (0.579 for the sagittal vertical axis and 0.585 for the T1 pelvic angle). Regression analysis revealed that anteversion decreased by 1° for each of the following spinopelvic parameter changes (p < 0.001): 1.105° for spinopelvic tilt, 1.032° for sacral slope, and 3.163° for lumbar lordosis. Patients with spinopelvic malalignment had a high prevalence of excessively anteverted acetabular components. Sagittal spinal correction following total hip arthroplasty resulted in reduced acetabular anteversion, which may have implications for stability. Changes in anteversion are most closely related to changes in pelvic tilt in an almost one-to-one ratio.


Plant species affect colonization patterns and metabolic activity of associated endophytes during phytoremediation of crude oil-contaminated soil.
Plants coupled with endophytic bacteria hold great potential for the remediation of polluted environment. The colonization patterns and activity of inoculated endophytes in rhizosphere and endosphere of host plant are among the primary factors that may influence the phytoremediation process. However, these colonization patterns and metabolic activity of the inoculated endophytes are in turn controlled by none other than the host plant itself. The present study aims to determine such an interaction specifically for plant-endophyte systems remediating crude oil-contaminated soil. A consortium (AP) of two oil-degrading endophytic bacteria (Acinetobacter sp. strain BRSI56 and Pseudomonas aeruginosa strain BRRI54) was inoculated to two grasses, Brachiaria mutica and Leptochloa fusca, vegetated in crude oil-contaminated soil. Colonization patterns and metabolic activity of the endophytes were monitored in the rhizosphere and endosphere of the plants. Bacterial augmentation enhanced plant growth and crude oil degradation. Maximum crude oil degradation (78%) was achieved with B. mutica plants inoculated with AP consortium. This degradation was significantly higher than those treatments, where plants and bacteria were used individually or L. fusca and endophytes were used in combination. Moreover, colonization and metabolic activity of the endophytes were higher in the rhizosphere and endosphere of B. mutica than L. fusca. The plant species affected not only colonization pattern and biofilm formation of the inoculated bacteria in the rhizosphere and endosphere of the host plant but also affected the expression of alkane hydroxylase gene, alkB. Hence, the investigation revealed that plant species can affect colonization patterns and metabolic activity of inoculated endophytic bacteria and ultimately the phytoremediation process.


Home advantage mediated (HAM) by referee bias and team performance during covid.
The fans' importance in sports is acknowledged by the term 'the 12th man', a figurative extra player for the home team. Sport teams are indeed more successful when they play in front of their fans than when they play away. The supposed mechanism behind this phenomenon, termed Home Advantage (HA), is that fans' support spurs home players to better performance and biases referees, which in turn determines the outcome. The inference about the importance of fans' support is, however, indirect as there is normally a 12th man of this kind, even if it is an opponent's. The current pandemic, which forced sporting activities to take place behind closed doors, provides the necessary control condition. Here we employ a novel conceptual HA model on a sample of over 4000 soccer matches from 12 European leagues, some played in front of spectators and some in empty stadia, to demonstrate that fans are indeed responsible for the HA. However, the absence of fans reduces the HA by a third, as the home team's performance suffers and the officials' bias disappears. The current pandemic reveals that the figurative 12th man is no mere fan hyperbole, but is in fact the most important player in the home team.


Ultrasonic nebulization headspace ionic liquid-based single drop microextraction of flavour compounds in fruit juices.
The ultrasonic nebulization headspace ionic liquid-based single drop microextraction was developed for the extraction of flavour constituents from fruit juices. The GC-MS was applied to the separation and detection of the constituents. The parameters affecting extraction performance, such as microdrop volume, extraction time, enrichment time, extraction temperature, and position of microdrop, were investigated and optimized. The optimized system was: ionic liquid, 1-hexyl-3-methylimidazolium tetrafluroborate; solvent microdrop volume, 12.5 μL; extraction time, 5 min; enrichment time, 20 min; extraction temperature, 80 °C; the height of the microdrop above the solution surface, 1cm; and, the pH value of sample solution did not affect the species, and solubility of analytes. The recoveries were in the range of 80.4-115.0%, and the relative standard deviations were lower than 9.1%. The present method is a simple and sensitive method for the determination of flavour constituents in fruit juices.


Modeling of Clostridium perfringens vegetative cell inactivation in beef-in-sauce products: a meta-analysis using mixed linear models.
The aim of the present study was to predict Clostridium perfringens vegetative cell inactivation during the final reheating step of two beef-in-sauce products prepared and distributed in a French hospital for exposure in risk assessment. In order to account for variability according to experts and international organization recommendations, published data were used to estimate the thermal inactivation parameters of a probabilistic model. Mixed effects models were proposed to describe variability on D(ref) the decimal reduction time at temperature T(ref). Many models differing by their description of variability on D(ref) were tested. Based on goodness-of-fit and parsimony of the model, the one including three random effects was chosen. That model describes random effects of vegetative cell culture conditions, strains and other uncontrolled experimental factors. In order to check the ability of the model to predict inactivation under dynamic thermal conditions, model validation was carried out on published non isothermal data. This model was then used to predict C. perfringens vegetative cell inactivation using temperature profiles inside beef-in-sauce products registered in a French hospital and to explore control measures easier to apply than French regulations.


A rapid radiochemical bacterial bioassay to evaluate copper toxicity in freshwaters.
A rapid, highly sensitive bacterial bioassay to determine copper toxicity in freshwaters was developed based on the inhibition of cellular assimilation of radiolabeled glucose. The test used a copper-sensitive bacterium isolated from a freshwater stream. Employing sensitive radiochemical techniques enabled environmentally relevant concentrations of the test bacterium (10(5) cells mL(-1)) and a short incubation period (4 hours) to be used, which minimized the potential for changes in copper speciation during the test. The 4-hour median effective concentration (EC(50)) for inorganic copper at pH 7.5 in synthetic freshwater was 0.6 microg L(-1) (95% confidence limits 0.4 to 1.0 microg L(-1)). This compared well with chronic growth inhibition of this bacterium in minimal medium (48-hour EC(50) of 0.9 microg L(-1) [95% confidence limits 0.7 to 1.0 microg L(-1)]). MINEQL + software (Environmental Research Software) was used to calculate copper (II) ion concentrations in synthetic freshwater at pH 7.5, giving an EC(50) value of pCu(2+) 8.8. However, using nitrilotriacetic acid metal-ion buffers (Cu-NTA), 50% inhibition occurred at a pCu(2+) of 9.7, suggesting this bacterium was markedly more inhibited by copper in these Cu(2+)-buffered solutions. This may indicate that the Cu-NTA species was contributing to toxicity. The radiochemical bioassay was evaluated further using freshwater samples from both copper-impacted and pristine environments. Measured EC(50) values ranged from 3.4 to 34.0 microg L(-1)inorganic copper and were strongly correlated with dissolved organic carbon (DOC) concentrations (r = 0.88, p < 0.05).


Spontaneous intramural oesophageal haematoma.
Six cases of spontaneous submucosal dissection of the oesophagus are described. This rare entity should be considered in patients presenting with chest pain, usually of sudden onset, associated with dysphagia and haematemesis. Barium swallow or endoscopy are needed to confirm the diagnosis and the characteristic features are described.


Ocular surface abnormalities in aniridia.
The purpose of this study was to examine ocular surface abnormalities in aniridia. We prospectively studied the ocular surface in nine consecutive patients (18 eyes) with virtually total aniridia. Of the 18 eyes, two eyes (two patients) were excluded from the study because severe surgical damage was likely to be the main cause of their corneal abnormalities. Six volunteers whose eye examinations yielded normal results served as control subjects. Detailed slit-lamp biomicroscopic examinations were performed to assess corneal findings and confirm the presence or absence of the palisades of Vogt. Goblet cell density on the peripheral corneal epithelium and inferior conjunctival epithelium was calculated via impression cytology and was statistically compared between aniridic eyes and control eyes. All 16 aniridic eyes had superficial corneal opacification and vascularization of either the peripheral or entire cornea. Palisades of Vogt were completely absent all around the limbal area. Goblet cell density on the peripheral cornea and inferior conjunctiva showed a statistically significant increase in the aniridic eyes (226 +/- 169 cells/mm2 and 406 +/- 203 cells/mm2), as compared with the control eyes (O cells/mm2 and 181 +/- 89 cells/mm2) (P = .0005 and P = .0102). These findings suggest that, in the aniridic eye, conjunctival epithelium invades the cornea because of corneal epithelial stem cell deficiency.


Mortality in people with mental disorders in Poland: A nationwide, register-based cohort study.
Mortality among people with mental disorders is higher in comparison with the general population. There is a scarcity of studies on mortality in the abovementioned group of people in Central and Eastern European countries. The study aimed to assess all-cause mortality in people with mental disorders in Poland. We conducted a nationwide, register-based cohort study utilizing data from two nationwide registries in Poland: the registry of healthcare services reported to the National Health Fund (2009-2018) and the all-cause death registry from Statistics Poland (2019). We identified individuals who were consulted or hospitalized in public mental healthcare facilities and received at least one diagnosis of mental disorders (International Statistical Classification of Diseases and Health Problems [ICD-10]) from 2009 to 2018. Standardized mortality ratios (SMRs) were compared between people with a history of mental disorder and the general population. The study comprised 4,038,517 people. The SMR for individuals with any mental disorder compared with the general population was 1.54. SMRs varied across diagnostic groups, with the highest values for substance use disorders (3.04; 95% CI 3.00-3.09), schizophrenia, schizotypal and delusional disorders (2.12; 95% CI 2.06-2.18), and pervasive and specific developmental disorders (1.68; 95% CI 1.08-2.29). When only inpatients were considered, all-cause mortality risk was almost threefold higher than in the general population (SMR 2.90; 95% CI 2.86-2.94). In Poland, mortality in people with mental disorders is significantly higher than in the general population. The results provide a reference point for future longitudinal studies on mortality in Poland.


Preparation of Entamoeba histolytica antigens without enzymatic inhibitors.
The goal of this work is to report a novel assay that preserves antigenicity of extracts with high protease content without using enzymatic inhibitors. A great reduction of proteolytic activity in the insoluble chloroform/methanol and heated amoebic fraction (IC:MC) was obtained by this method, even in the presence of sodium dodecyl sulphate and 2-mercaptoethanol. The substrates azo-casein and the hide powder azure were used to determine the reduction of proteolytic activity of IC:MC compared with the activity of crude extract and crude extract with iodoacetamide. The IC:MC SDS-PAGE pattern shows a higher quantity of bands than extract with the inhibitor iodoacetamide or than crude extract. In addition, anti-Entamoeba histolytica antibodies from amoebic liver abscess patients recognized a richer antigenic Western blot pattern in the IC:MC fraction than in crude extract alone or with inhibitor. The described method has proved to be suitable to preserve amoebic antigens for its use in diagnostic tests and it can be used for immunological response studies against E. histolytica antigens. Furthermore we propose that this method to obtain the IC:MC fraction can be applied for the study of other microorganisms or cells with high enzymatic content.


Ivermectin and curcumin cause plasma membrane rigidity in Leishmania amazonensis due to oxidative stress.
Spin label electron paramagnetic resonance (EPR) spectroscopy was used to study the mechanisms of action of ivermectin and curcumin against Leishmania (L.) amazonensis promastigotes. EPR spectra showed that treatment of the parasites with both compounds results in plasma membrane rigidity due to oxidative processes. With the IC50 and EPR measurements for assays using different parasite concentrations, estimations could be made for the membrane-water partition coefficient (KM/W), and the concentration of the compound in the membrane (cm50) and in the aqueous phase (cw50), which inhibits cell growth by 50%. The KM/W values indicated that ivermectin has a greater affinity than curcumin for the parasite membrane. Therefore, the activity of ivermectin was higher for experiments with low cell concentrations, but for concentrations greater than 1.5 × 108 parasites/mL the compounds did not show significantly different results. The cm50 values indicated that the concentration of compound in the membrane leading to growth inhibition or membrane alteration is approximately 1 M for both ivermectin and curcumin. This high membrane concentration suggests that many ivermectin molecules per chlorine channel are needed to cause an increase in chlorine ion influx.


Urinary Tract Infection in Children: Management in the Era of Antibiotic Resistance-A Pediatric Urologist's View.
Antibiotic resistance to uropathogens has grown significantly worldwide. Today, pediatric urologist experience a situation that needs appropriate action because urinary tract infections are one of the most common bacterial infections in children. In this overview we aimed at presenting the clinical aspects of antibiotic usage in pediatric urology. Our intention was to take part of the important debate regarding future management of bacterial resistance against antibiotics. We searched PubMed for the terms: [UTI in children], [Recurrent UTI in children], and [Antibiotic resistance in UTI]. When using these terms, we found a numerous amount (3875) of published clinical articles related to the topic. By means of an overview, we chose not to focus on a specific condition but to an overall understanding of the problems related to pediatric urology in general. We found that usage of antibiotics has had an unquestionable benefit to reduce the morbidity and mortality related to urinary tract infections in childhood. However, recent studies suggest that early exposure to antibiotics in childhood might have negative systemic effects related to neurocognitive function, body metabolism, and fat distribution. In addition to increased resistance to common antimicrobial agents, it has resulted in increased costs and inadequate effect in severe infections. This calls for changes in the clinical management of urinary pathogens in pediatric urology. As the prevalence of antibiotic resistance grows, pediatric urologists have a key role in managing its consequences and its prevention. In this overview we looked at the consequences of antibiotic usage treating urinary tract infections in childhood. We found that the prevalence of antibiotic resistance has grown. We concluded that decision-makers must know about the short- and long-term effects of antibiotic usage in children. When we understand the development of antibiotic resistance better, we can build up prevention strategies.


Quercus salicina Blume: Research Progress in Chemistry and Pharmacodynamics (1959-2021).
The crude extracts of different parts (leaves and shoots) of Quercus salicina Blume (QS) have shown considerable effect in urolithiasis. QS has been widely used in clinical practice and has attracted great research interest The relevant published literature, however, reveals only partial education of its chemical components and bio-active mechanisms, and only two review articles have summarized the QS research progress. In this review, a comprehensive and systematic review of chemistry and pharmacodynamics of QS was carried out using the international authoritative databases (1959-2021), focusing on phenols and flavonoids, and their effect such as urinary stone dissolution, anti-inflammatory, anti-diabetes, anti-bacterial, antioxidant, and anti-allergy activities as well as toxic effects. The aim of review is to provide the most recent and effective literature support for further basic research and application development.


Drugs and exercise.
In this article, we have examined some pharmacologic principles as they apply to drug use by healthy individuals. With the present emphasis on community activities, we have dealt with the impairment of thermoregulation by athletes and fun runners who may take normal over-the-counter medications for a variety of reasons. However, many of these drugs impair thermoregulation. Our additional focus has been on drug abuse, again by healthy people, often striving to enhance their performance. Here we have dealt principally with the anabolic and androgenic steroids and stimulants. Finally, we have reproduced the current list of medications permitted by the International Olympic Committee, but have also offered some suggestions of common medications that may be required by athletes for such illnesses as hay fever, upper respiratory tract infections, and other simple disorders (Table 2). These medications do not contain any ingredients prohibited by the International Olympic Committee regulations. It is important to remember that many of the compound medications often sold over-the-counter contain substances such as caffeine, codeine, and ephedrine, which the unwitting athlete, trainer or coach could prescribe for a legitimate indication but which could, and have in the past, cost such athletes Olympic medals.


Chemical stabilization of the phycocyanin from cyanobacterium Spirulina platensis.
Phycocyanin (PC) prepared from a cyanobacterium Spirulina platensis by the DEAE-DE52 cellulose column chromatography that was developed by gradient elution of 50-250 mM phosphate buffer (pH 7.0) was stabilized by its subunits cross-linked covalently with formaldehyde. The single blue band that the chemically stabilized PC showed in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that the stabilized PC still maintained its trimeric aggregate form even after its incubation at 60 degrees C for 3h and at 100 degrees C for 10 min in the denatured buffer containing 5% (w/v) SDS. Moreover, the stabilized PC exhibited similar spectroscopic properties of absorption and fluorescence to those of the native PC, and showed adequate energy coupling with R-phycoerythrin (R-PE) after it was conjugated with R-PE via glutaraldehyde.


Clinical characteristics and cardiovascular risk profile in children and adolescents with latent autoimmune diabetes: Results from the German/Austrian prospective diabetes follow-up registry.
To characterize children and adolescents with latent autoimmune diabetes of the young (LADY), and to assess the utility of classifying individuals as LADYs regarding their cardiovascular (CV) risk factors. Data from 25,520 individuals (age at diagnosis <18 years) of the Prospective Diabetes Follow-up Registry Diabetes-Patienten Verlaufsdokumentation (DPV) were analyzed. LADY was defined as positivity of ≥one islet autoantibody (iAb+) and an insulin-free interval of ≥6 months upon diabetes diagnosis. LADYs were compared to iAb+ individuals immediately requiring insulin ("immunologically confirmed" type 1 diabetes, T1DM), iAb-/Ins- individuals ("classical" T2DM) and to those clinically defined as T2DM (iAbs not measured). Clinical characteristics of LADYs (n = 299) fell in between those with T1DM (n = 24,932) and T2DM (iAb-/Ins-, n = 152) or suspected T2DM (iAB not measured, n = 137). Stratifying LADYs according to their clinical diagnosis however revealed two distinct populations, highly resembling either T1DM or T2DM. Particularly, CV risk profile, precisely prevalence rates of arterial hypertension and dyslipidemia, was significantly higher in LADYs clinically classified as T2DM compared to LADYs classified as T1DM, and did not differ from those with "classical" T2DM. In terms of CV risk, classifying children and adolescents with diabetes as LADYs provides no additional benefit. Instead, clinical diagnosis seems to better assign individuals to appropriate risk groups for increased CV risk profiles.


Success Using Neuromodulation With BURST (SUNBURST) Study: Results From a Prospective, Randomized Controlled Trial Using a Novel Burst Waveform.
The purpose of the multicenter, randomized, unblinded, crossover Success Using Neuromodulation with BURST (SUNBURST) study was to determine the safety and efficacy of a device delivering both traditional tonic stimulation and burst stimulation to patients with chronic pain of the trunk and/or limbs. Following a successful tonic trial, 100 subjects were randomized to receive one stimulation mode for the first 12 weeks, and then the other stimulation mode for the next 12 weeks. The primary endpoint assessed the noninferiority of the within-subject difference between tonic and burst for the mean daily overall VAS score. An intention-to-treat analysis was conducted using data at the 12- and 24-week visits. Subjects then used the stimulation mode of their choice and were followed for one year. Descriptive statistics were used analyze additional endpoints and to characterize the safety profile of the device. The SUNBURST study demonstrated that burst stimulation is noninferior to tonic stimulation (p < 0.001). Superiority of burst was also achieved (p < 0.017). Significantly more subjects (70.8%) preferred burst stimulation over tonic stimulation (p < 0.001). Preference was sustained through one year: 68.2% of subjects preferred burst stimulation, 23.9% of subjects preferred tonic, and 8.0% of subjects had no preference. No unanticipated adverse events were reported and the safety profile was similar to other spinal cord stimulation studies. The SUNBURST study demonstrated that burst spinal cord stimulation is safe and effective. Burst stimulation was not only noninferior but also superior to tonic stimulation for the treatment of chronic pain. A multimodal stimulation device has advantages.


Nonsurgical Management of Temporomandibular Joint Arthropathy.
Arthropathy is a broad diagnostic term for any pathologic condition afflicting one or more joints of the body. Temporomandibular joint (TMJ) arthropathy is an umbrella term that may be applied to mechanical dysfunction or disease of one or both TMJs. This article provides evidence-based recommendations for conducting a patient evaluation, initiating a diagnostic workup, formulating an assessment, and instituting various nonsurgical modalities for the treatment of TMJ arthropathies.


Dulaglutide and Insulin: How Can the AWARD Studies Help Guide Clinical Practice?
The glucagon-like peptide 1 receptor agonist (GLP-1RA) dulaglutide has many characteristics to recommend it both as a second-line agent and as an alternative to or in combination with insulin. This commentary summarises recent updates to diabetes management guidelines regarding the use of GLP-1RAs such as dulaglutide, both as a second-line agent and as a first-line injectable agent in type 2 diabetes (T2D). It also examines how the Assessment of Weekly AdministRation of LY2189265 [dulaglutide] in Diabetes (AWARD) studies with dulaglutide and insulin may help to guide clinical practice for the use of dulaglutide as an alternative to basal insulin or in combination with insulin.Individualising glucose-lowering therapy is important in patients with T2D, especially given patients' heterogeneity in terms of age, lifestyle, disease duration, level of hyperglycaemia and comorbidities. Choice of therapy should be guided by clinical considerations (e.g. high risk or existing cardiovascular [CV] disease, heart failure, chronic kidney disease, risk of hypoglycaemia), side effect profile, contraindications, patient preferences and cost. The recently updated American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) guidelines now recommend adding a GLP-1RA with proven CV benefit to metformin in patients with T2D and indicators of high risk or established atherosclerotic CV disease. The AWARD studies demonstrate that dulaglutide provides effective glucose lowering together with sustained weight loss and a low incidence of hypoglycaemia when used as the first injectable option and when used in combination with titrated basal insulin or prandial insulin, providing a valid treatment option across a wide range of patients with T2D, including those with chronic kidney disease.


First report of Giardia duodenalis in pet rabbits in Brazil.
Giardia duodenalis is a flagellate protozoan that multiplies in the small intestine of a wide variety of hosts, animals and humans. It has a worldwide distribution, however it is considered a neglected disease by the World Health Organization (WHO). Nowadays, rabbits are being chosen as pets, especially by children. There are already reports of the occurrence of G. duodenalis in rabbits from other countries, but research has not been carried out in Brazil yet. Thus, the objective of our work was to verify the occurrence and molecularly characterize G. duodenalis that affect pet rabbits, through the polymerase chain reaction (PCR) in the northwest region of the state of São Paulo, Brazil. Fecal samples from 100 rabbits were collected, which later underwent a process of DNA extraction and amplification by nested-PCR (nPCR), using the SSU rRNA gene, and β-giardin (bg), glutamate dehydrogenase (gdh) and triosephosphate isomerase (tpi) to determine the assemblage. A questionnaire was answered by the owners with information about gender, age, deworming, diarrhea, water source, food, place of residence and contact with other animals. From those samples, 40 were positive for G. duodenalis. Good quality of the SSU rRNA gene by nPCR were obtained from two samples. For the first time, we report the occurrence of G. duodenalis assemblage A on pet rabbits in Brazil.


Arbuscular mycorrhizal fungal diversity in soils underlying moss biocrusts in coal mining subsidence areas.
The potentially symbiotic mycorrhizal associations dominated by arbuscular mycorrhizal (AM) fungi have become a new topic in bioremediation research in response to global change. Biological soil crusts (biocrusts) play an important role in arid and semi-arid ecosystems. However, AM fungal diversity in the soils underlying moss biocrusts in coal mining subsidence areas remains poorly understood. Here, samples of the soil underlying moss biocrusts in an area inoculated with an AM fungus (AM-BS) and an uninoculated area (CK-BS) plus soil samples from an uninoculated bare area (CK-NBS) were collected from the subsidence area of Shendong Daliuta mine at Yulin, northwest China. AM fungal community diversity indices were maximum in AM-BS, intermediate in CK-BS, and minimum in CK-NBS (P < 0.05). In addition, redundancy analysis (RDA) indicates that the importance of moss biocrust to soil properties followed the sequence: soil water content (SWC) > glomalin-related soil protein (TG) > available phosphorus (Olsen-P) > soil organic matter (SOM) > easily extractable glomalin-related soil protein (EEG) > pH > available nitrogen (alkali-N). SWC, alkali-N, Olsen-P, and SOM were significantly related to the abundance of Glomus and Claroideoglomus, and TG, EEG, and pH were positively related to Diversisipora. In summary, inoculation with the exotic AM fungus and moss biocrust cover created a eutrophic microhabitat for AM fungi in the soils underlying moss biocrusts in the coal mining subsidence area.


Long-term treadmill exercise inhibits the progression of Alzheimer's disease-like neuropathology in the hippocampus of APP/PS1 transgenic mice.
Previously our study has demonstrated that long-term treadmill exercise improved cognitive deficit in APP/PS1 transgenic mice of Alzheimer's disease (AD) paralleled by enhanced long-term potentiation (LTP). The present study was undertaken to further investigate whether the treadmill running could inhibit the progression of Alzheimer's disease (AD)-like neuropathology in hippocampus of the APP/PS1 mouse models of AD, and to define a potential molecular mechanism underlying the exercise-induced reduction in AD-like neuropathology. Five months of treadmill exercise resulted in a robust reduction in β-amyloid (Aβ) deposition and tau phosphorylation in the hippocampus of APP/PS1 mice. This was accompanied by a significant decrease in APP phosphorylation and PS1 expression. We also observed GSK3, rather than CDK5, was inhibited by treadmill exercise. These results indicate that treadmill exercise is sufficient to inhibit the progression of AD-like neuropathology in the hippocampus of APP/PS1 transgenic mouse model, and may mediate APP processing in favor of reduced Aβ deposition. In addition, we demonstrate that treadmill exercise attenuates AD-like neuropathology in AD transgenic mice via a GSK3 dependent signaling pathway.


Soluble Siglec-9 alleviates intestinal inflammation through inhibition of the NF-κB pathway.
Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a superfamily of immunoreceptors recognizing sialic acid. Siglec-9 has been shown to mediate inhibitory immune responses. The aim of this study was to evaluate the effect of a soluble form of Siglec-9 (sSiglec-9) on inflamed intestinal epithelial cells (IECs), murine macrophages, and experimental murine colitis models. COLO 205 human IECs and RAW 264.7 murine macrophages were pretreated with sSiglec-9 and then stimulated with TNF-α or lipopolysaccharides, respectively. The expression of proinflammatory cytokines such as IL-8 and TNF-α was measured using real-time RT-PCR and ELISA. To demonstrate the inhibitory effects of sSiglec-9 on the NF-κB pathway, IκBα phosphorylation/degradation was determined using western blotting and the DNA binding activity of NF-κB was evaluated using an electrophoretic mobility shift assay. Further, mouse models with dextran sulfate sodium-induced acute colitis and piroxicam-induced IL-10-/- chronic colitis were generated. Intraperitoneal injections of sSiglec-9 were performed, and body weight, colon length, and histopathologic findings were examined. sSiglec-9 suppressed IL-8 and TNF-α gene expression in stimulated COLO 205 and RAW 264.7 cells. sSiglec-9 inhibited IκBα phosphorylation/degradation and the DNA binding activity of NF-κB. sSiglec-9 injections significantly ameliorated weight loss, colon shortening, and the severity of intestinal inflammation in acute and chronic colitis mouse models. sSiglec-9 may inhibit NF-κB activation in IECs and macrophages and alleviate experimental colitis in mice, suggesting that sSiglec-9 is a potential therapeutic agent for the treatment of inflammatory bowel disease.


A Participatory Comic Book Workshop to Improve Youth-Friendly Post-Rape Care in a Humanitarian Context in Uganda: A Case Study.
Graphic medicine formats, such as comic books in which health information is presented alongside images, may be a useful learning tool to improve post-rape care and youth-friendly service provision among health care providers in humanitarian contexts. We describe the development and pilot-testing of a workshop using a comic book to improve youth-friendly post-rape care with providers in Bidi Bidi refugee settlement, Uganda. We conducted 6 focus groups with refugee young men (n=3) and women (n=3) aged 16-24 years and 28 in-depth individual interviews (refugee youth: n=12; health care providers: n=8; elders: n=8). Findings informed the development of a workshop that included a participatory comic book on sexual and gender-based violence (SGBV) and youth, SGBV stigma, youth-friendly health care, and post-exposure prophylaxis. Comic book illustrations specifically addressed health care confidentiality and examples of being a supportive health care provider. Then, we conducted a 1-day workshop with health care providers (n=20) that included structured activities addressing SGBV impacts and related stigma and included comic book discussions. Open-ended survey data were collected 8 weeks after the workshop to explore health care providers' experiences with the workshop, perceived impact of the intervention on their work, and support required to implement youth-friendly services for SGBV survivors. Qualitative data were analyzed using thematic approaches. Open-ended response data indicated that: comic book methods were informative and interactive; health care providers felt more empowered to offer youth-friendly services and spaces; and health care providers want additional SGBV training and institutional support for youth-friendly spaces and community engagement. A comic book intervention has the potential to meaningfully engage health care providers in humanitarian contexts to provide youth-friendly health care, acquire skills for engaging in SGBV prevention, create youth-friendly clinic spaces, and identify health care and community SGBV prevention needs.


Role of relative size of asperities and adhering particles on the adhesion force.
Adhesion force between silica microspheres of different sizes and different rough surfaces (silicon and diamond like carbon) has been measured with an atomic force microscope (AFM). Surface roughness, asperity geometry, and size of adhering particles play an important role in determining the adhesion force. Adhesion force linearly increases with size of adhering particle for smooth surfaces and can be described by the JRK model. Adhesion force of adhering particle bigger than in size to the asperities decreases with surface roughness and can be described by the Rabinovich model. For the particles smaller than or similar in size to the asperities, the adhesion force increases with surface roughness. In later case, the interaction of adhering particles with valley portion of asperities is dominated and the contact area increases. On the basis of Rabinovich model, a new equation, which takes the relative size of adhering particles and asperities into account, is derived and compared with experimental results. The normalized adhesion force decreases with ratio of root-mean-square (rms) roughness to radius of adhering particle up to 0.0025, followed by increasing normalized adhesion forces.


1H-1H correlations across N-H...N hydrogen bonds in nucleic acids.
In 2HJ(NN)-COSY experiments, which correlate protons with donor/acceptor nitrogens across Nd...HNa bonds, the receptor nitrogen needs to be assigned in order to unambiguously identify the hydrogen bond. For many situations this is a non-trivial task which is further complicated by poor dispersion of (Na,Nd) resonances. To address these problems, we present pulse sequences to obtain direct, internucleotide correlations between protons in uniformly 13C/15N labeled nucleic acids containing Nd...HNa hydrogen bonds. Specifically, the pulse sequence H2(N1N3)H3 correlates H2(A,omega1):H3(U,omega2) protons across Watson-CrickA-U and mismatched G.A base pairs, the sequences H5(N3N1)H1/H6(N3N1)H1 correlate H5(C,omega1)/H6(C,omega1):H1(G,omega2) protons across Watson-Crick G-C base pairs, and the H2(N2N7)H8 sequence correlates NH2(G,A,C;omega1):H8(G,A;omega2) protons across G.G, A.A, sheared G.A and other mismatch pairs. These 1H-1H connectivities circumvent the need for independent assignment of the donor/acceptor nitrogen and related degeneracy issues associated with poorly dispersed nitrogen resonances. The methodology is demonstrated on uniformly 13C/15N labeled samples of (a) an RNA regulatory element involving the HIV-1 TAR RNA fragment, (b) a multi-stranded DNA architecture involving a G.(C-A) triad-containing G-quadruplex and (c) a peptide-RNA complex involving an evolved peptide bound to the HIV-1 Rev response element (RRE) RNA fragment.


Vascular Compromise After Soft Tissue Facial Fillers: Case Report and Review of Current Treatment Protocols.
The use of facial fillers for soft tissue augmentation is becoming a mainstream treatment modality for patients. Owing to the relative ease of administration, as well as the lucrative nature of such procedures, the number of providers offering facial fillers has been expanding. Although many adverse effects of facial fillers are minor and localized to the site of injection, 1 potential serious, albeit uncommon, adverse effect of facial filler treatment is avascular necrosis. In this article, we review soft tissue filler complications and describe the case of a 52-year-old female patient in whom vascular compromise developed after facial filler administration. In addition to reviewing complications and best practices for treatment management, we discuss anatomic considerations, present an overview of the most common filler materials, describe histologic changes with dermal fillers, and discuss litigation consequences with the use of these minimally invasive procedures. Although facial filler treatment is regarded as a minimally invasive and extremely safe procedure, it is not without complications. Avascular necrosis after soft tissue augmentation with facial fillers is exceedingly rare, with only a few cases reported in the literature, but practitioners who offer this procedure need to be well versed in treatment protocols.


Differences in current amplitude evoking leg extension in individuals with spinal cord injury.
To investigate the effects of regional thigh composition that result in different responses to current amplitude among individuals with spinal cord injury (SCI) during applications of surface neuromuscular electrical stimulation (NMES) to evoke dynamic leg extension. Cross-sectional. Academic Settings. Five males with chronic motor complete SCI completed 3 visits of NMES to determine the current amplitude required to evoke full knee extension. The participants underwent magnetic resonance imaging of both thighs to measure skeletal muscle cross-sectional area (CSA), thigh subcutaneous adipose tissue (SAT) and intramuscular fat (IMF). Applicants were classified into high (n = 3) and low-responders (n = 2) based on the determined current amplitude. The low-responders required 48-59% greater current amplitude to complete the same task as the high-responders. Low-responders had greater thigh SAT CSA (51-56%) than the high-responders with SCI. After adjusting to whole thigh CSA, IMF CSA was significantly greater in the low- responders; whereas skeletal muscle CSA was lower compared to the high-responders. The findings suggest that thigh SAT and IMF act as insulation against propagation of current during surface NMES applications in individuals with SCI.


Galanin-like peptide stimulates food intake in the rat.
We have isolated a novel hypothalamic peptide, Galanin-like peptide (GALP), as a ligand for galanin receptor subtype GalR2. To investigate the physiological role of GALP, we examined the effect of the intracerebroventricular administration of GALP and found that GALP induced food intakes. GALP had ten-fold the orexigenic activity of galanin. We also observed the anxiogenic-like behavior after the administration of 1 nmol GALP. These results suggest that GALP is a novel orexigenic and anxiogenic peptide.


Community-acquired bacteremia among hospitalized children in rural central Africa.
To describe the epidemiology of community-acquired bacteremia in children admitted to a rural hospital in central Africa and to identify useful diagnostic signs or symptoms. On admission, a blood culture was obtained from all children admitted to Children's Hospital of Lwiro between 1989 and 1990. Clinical and biologic signs of infection and nutritional status were recorded. Among the 779 children included in the study, 15.9% were bacteremic on admission. The rate of bacteremia was the highest among children with jaundice (20/56; 35.7%) and fever (119/487; 24.4%). In contrast, children with severe malnutrition had a lower rate of bacteremia (13.2%) than weight growth retarded or well-nourished children (19.5%) (P = 0.046). Fever was the most useful diagnostic criteria (sensitivity and negative predictive value of 96.0% and 97.8%, respectively) even in severely malnourished children (sensitivity and negative predictive value of 96.4% and 99.1%, respectively). Enterobacteriacea, mostly Salmonella spp, caused 73% of the bacteremia. There was a high rate of resistance to ampicillin and chloramphenicol among the responsible organisms. Only 31 (47.7%) of 65 bacteremic children responded to the combination of ampicillin and gentamicin. The presence of bacteremia on admission did not significantly increase the risk of morality during hospitalization (19.4% compared with 13.5%; P = 0.088). Age less than 12 months and jaundice were independent risk factors for deaths in bacteremic children. Community-acquired bacteremia caused by multiresistant Enterobacteriacea is an important problem of hospitalized well-nourished and malnourished children in central Africa. Fever on admission is a sensitive diagnostic sign, even in malnourished children.


Recent Update on Bacteria as a Delivery Carrier in Cancer Therapy: From Evil to Allies.
Cancer is associated with a comprehensive burden that significantly affects patient's quality of life. Even though patients' disease condition is improving following conventional therapies, researchers are studying alternative tools that can penetrate solid tumours to deliver the therapeutics due to issues of developing resistance by the cancer cells. Treating cancer is not the only the goal in cancer therapy; it also includes protecting non-cancerous cells from the toxic effects of anti-cancer agents. Thus, various advanced techniques, such as cell-based drug delivery, bacteria-mediated therapy, and nanoparticles, are devised for site-specific delivery of drugs. One of the novel methods that can be targeted to deliver anti-cancer agents is by utilising genetically modified non-pathogenic bacterial species. This is due to the ability of bacterial species to multiply selectively or non-selectively on tumour cells, resulting in biofilms that leads to disruption of metastasis process. In preclinical studies, this technology has shown significant results in terms of efficacy, and some are currently under investigation. Therefore, researchers have conducted studies on bacteria transporting the anti-cancer drug to targeted tumours. Alternatively, bacterial ghosts and bacterial spores are utilised to deliver anti-cancer drugs. Although in vivo studies of bacteria-mediated cancer therapy have shown successful outcome, further research on bacteria, specifically their targeting mechanism, is required to establish a complete clinical approach in cancer treatment. This review has focused on the up-to-date understanding of bacteria as a therapeutic carrier in the treatment of cancer as an emerging field.


Sterilization incentives and associated regret among ever married women in India, NFHS, 2015-16.
Sterilization is the only family planning method that involves relatively large amount compensation. So, the study attempts to examine the role of incentives received against the sterilization procedures on the reporting of sterilization regret in India. The study used data from the fourth round of National Family Health Survey, 2015-16, which gathered the information on sterilization regret from 1,94,207 ever-married women. Multivariate logistic analysis and predicted probabilities approach was used to study the effect of compensation received on the sterilization regret in India. Results show that women who have received compensation were 33% less likely to report sterilization regret. It was found that 70% of women who undergone sterilization in public facility didn't incur any expenditure, rather received incentives. It is observed that women who had undergone operation in private facility spent a large amount than women who had done their operation in public facility. The regret in the private facility mainly results from high out of pocket expenditure on sterilization procedures. Around eight percent of women regretted getting sterilized in a private hospital and received some compensation amount, vis a vis the six percent who regretted undergoing sterilization in public facility and received compensation. The study calls for a need to standardize the cost of sterilization procedure in India's health facilities. A good alternative for reducing the cost could be Public-Private Partnership.


Lymphocyte activation after exposure to swine dust: a role of humoral mediators and phagocytic cells.
Exposure to swine dust causes intense airway inflammation with multifold increase in inflammatory cells and secretion of pro-inflammatory cytokines. This in vitro study focuses on the swine-dust activation of lymphocytes in whole blood, in phagocyte-depleted whole blood and in peripheral blood mononuclear cells (PBMC), in order to investigate whether phagocytic cells and/or soluble mediators are involved in the activation of T-cells following exposure to organic dust from a swine confinement house. T-cell activation was analysed by flow cytometry with double staining for CD3 and the activation marker CD69. Swine dust (50 microg) incubated (24 h) with heparinized whole blood was shown to activate 27.6% of the T-cells, while swine dust incubated with whole blood depleted from phagocytic cells or PBMC only activated 4.5%, and 4.8% of the T-cells, respectively. Plasma separated from whole blood preincubated with swine dust for 24 h stimulated as much as 32.4% of PBMC T-cells and contained high levels of interleukin (IL)-12 (14 pg x mL) and interferon (IFN)-gamma (2284 pg x mL(-1)), while plasma from PBMC incubated with swine dust contained low levels of IL-12 (2 pg x mL(-1)) and IFN-gamma (196 pg x mL(-1)). This study demonstrates that activation of T-cells by organic dust from a swine confinement building seems to require phagocytic cells, most likely acting through the release of soluble mediators. Also, conditioned plasma from swine-dust exposed whole blood, which was capable of activating T-cells, contained high concentrations of interleukin-12 and interferon-y.


Increased gelatinase B/matrix metalloproteinase 9 (MMP-9) activity in a murine model of acute coxsackievirus B4-induced pancreatitis.
Infection of mice with coxsackievirus B4 results within days in a severe acute necrotizing pancreatitis, which resolves completely within weeks. Gelatinase B or matrix metalloproteinase 9 (MMP-9) has previously been shown to be involved in several models of pancreatitis, but its role in virus-induced pancreatitis has never been investigated. We here report that MMP-9 levels are markedly increased in the pancreas of mice that developed acute pancreatitis following infection with coxsackievirus B4. Moreover, using in situ zymography, we demonstrated that MMP-9 is active in vivo. Double immunohistochemical analysis revealed that macrophages and neutrophils were the cellular source of MMP-9. Extensive tissue rearrangements involving collagen turnover were observed, and these were associated with extensive pathology and resolution of the disease. In summary, this report demonstrates that acute coxsackievirus B4-induced pancreatitis involves the action of MMP-9, which is mainly originating from macrophages and neutrophils.


Baseline and early changes in the neutrophil-lymphocyte ratio (NLR) predict survival outcomes in advanced colorectal cancer patients treated with immunotherapy.
Systemic inflammation plays a role in carcinogenesis and is related to overall survival in patients with different cancer types, including those treated with immune checkpoint blockade (ICB). The neutrophil-lymphocyte ratio (NLR) is calculated by circulating neutrophil to lymphocyte counts, which represents an indicator of the balance between the deleterious roles of neutrophilia and the beneficial roles of lymphocyte-mediated immunity. We hypothesized that the NLR may predict outcomes in metastatic colorectal cancer (mCRC) patients treated with immunotherapy. This retrospective study included 110 mCRC patients who were treated with immunotherapy at Sun Yat-sen University Cancer Center. Several inflammatory biomarkers were measured at baseline and after two cycles of treatment. The X-tile program was used to obtain the cutoff values. We examined the impact of both baseline and posttreatment inflammatory index levels on overall survival (OS). In univariate analysis, both a low baseline NLR (P = 0.014) and a decreased NLR after 2 cycles of immunotherapy (P < 0.001) were considerably correlated with better OS. In multivariate analysis, age, liver metastasis, baseline lymphocyte-monocyte ratio (LMR), baseline NLR and early changes in NLR independently predicted OS. Patients with both a low baseline NLR and an early NLR reduction had the longest OS (median, 29.63 months). The best outcomes were remarkably observed in patients who had both an early NLR reduction and a high tumor mutational burden (TMB) (≥10 mut/Mb) (P < 0.0001). Both a low baseline NLR and an early NLR reduction are significantly associated with a better prognosis in mCRC patients treated with immunotherapy. Further analysis indicated that the combination of NLR and TMB could obtain additional predictive power.


Identification of a novel mutation of the NTRK1 gene in patients with congenital insensitivity to pain with anhidrosis (CIPA).
Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disorder resulting from NTRK1 mutation. Over 105 NTRK1 mutations have been reported in CIPA patients worldwide. The causative NTRK1 mutations lead to loss of function of the TrkA protein, an important ligand for nerve growth factor (NGF), and therefore induce various clinical phenotypes associated with neuron maturation defects. Three patients from unrelated families with CIPA were subjected to detailed clinical examinations. Blood samples were collected from all the patients and their available family members, as well as 200 healthy volunteers. Sanger sequencing for all the exons and splicing sites of NTRK1 was performed on all samples. The phenotype-genotype relationship and genetic epidemiology of Chinese CIPA patients were also analysed. A total of four different NTRK1 mutations [c.851-33T>A, c.44G>A (p.Trp15*), c.287+2dupT, c.1549G>C (p.Gly517Arg)] were identified in these families, and c.1549G>C (p.Gly517Arg) was a novel mutation that had not been reported previously. The 'mild' manifestations observed in patients with c.851-33T>A indicated this mutation as a 'mild' mutation. After reviewing studies reporting mutations in Chinese CIPA patients, we speculate the mutation c.851-33T>A is one of the founder mutations in the Chinese population. Our research expanded the spectrum of the NTRK1 mutations associated with CIPA patients, provided additional clues relating to the phenotype-genotype relationship in CIPA, and summarized the features of the genetic epidemiology of CIPA in the Chinese ethnic group.


[Modification of the antiradical defense system of the organism under the influence of the administration of a leukocyte factor in the rabbit. Its relation to the increase of radioresistance by biostimulants].
Injection in the rabbit of the leucocyte endogenous mediator (LEM) liberated by activated granulocytes provokes after 24 h an increase in the glutathione concentration, particularly in the spleen and in the kidney, as well as an increase in acute phase proteins and modifications of the zinc concentration in the plasma, the liver and the kidney. These modifications are compared with those provoked by non specific biostimulants which increase the radioresistance during periods varying from several days to several weeks. It may be that LEM or a component accompanying it in the injected fraction is a factor intervening in the increase in radioresistance caused by biostimulants.


1,25-Dihydroxyvitamin D3 potentiates the decreased response of lymphocytes from atopic subjects to agents that increase intracellular cyclic adenosine monophosphate.
The inhibitory effect of prostaglandin E2, histamine, isobutylmethylxanthine, and 1,25-dihydroxyvitamin D3 (1,25-[OH]2D3) on the mitogenic stimulation of peripheral blood lymphocytes from normal and atopic subjects was studied. We found that lymphocytes from atopic patients were less susceptible to inhibition by the three agents that elevate intracellular cyclic adenosine monophosphate (cAMP) concentrations and by the active metabolite of vitamin D (inhibition of 27%, 14%, 12%, and 36% for the atopic patients as compared with 40%, 20%, 22%, and 46% for the normal donors, by the four agents, respectively; p less than 0.02). The inhibitory effect of the cAMP-elevating agents was potentiated by the addition of 1,25-(OH)2D3 to the lymphocyte cultures. The potentiation was more pronounced on lymphocytes from the atopic donors, increasing their responsiveness to levels comparable to levels of lymphocytes from normal donors. The synthetic corticosteroid, dexamethasone, had a similar potentiating effect on the inhibitory action of prostaglandin E2. In view of the beneficial action of beta-agonists, phosphodiesterase inhibitors, and corticosteroids in the treatment of allergy, the potentiating effect of 1,25-(OH)2D3 on the action of cAMP-elevating agents may be of therapeutic interest.


Involvement of cyclic AMP-dependent and -independent mechanisms in the relaxation of rat detrusor muscle via beta-adrenoceptors.
We investigated the cAMP-dependent and -independent mechanisms of relaxation via beta-adrenoceptor in rat detrusor muscle with and without pre-contraction. A microdialysis technique was used to measure detrusor tension and cAMP level on the same detrusor tissue. In non-contracted tissue, isoproterenol, clenbuterol (beta2-adrenoceptor agonist) and FR165101, ((8S)-8-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)oxy]acetic acid hydrochloride (beta3-adrenoceptor agonist) relaxed detrusor muscle and cAMP levels also increased in a concentration dependent manner. SQ22536 (adenylyl cyclase inhibitor) markedly suppressed relaxation, suggesting that beta-adrenoceptor-mediated relaxation may be attributed mainly to cAMP-dependent mechanism. In high K+ pre-contracted tissue, although relaxation advanced in a concentration dependent manner, cAMP production reached a plateau at concentrations of more than 10(-7) M. SQ22536 had only a small inhibitory effect. However, large-conductance, Ca2+-activated K+ (BK(Ca)) channel inhibitors, charybdotoxin and iberiotoxin markedly suppressed relaxation. These results suggest that in addition to cAMP-dependent pathway, BK(Ca) channels are involved in the beta-adrenoceptor agonists-induced relaxation in pre-contracted detrusor muscle.


Suppression of kindled seizures by cysteamine: dependence on injection-to-kindled seizure interval.
A single injection of cysteamine, 200 mg/kg i.p., administered 4 h before a kindling session induces long-term suppression of kindled seizures. Injection of cysteamine 2, 4 or 6 h after or 24 h before the kindling session is either less effective or ineffective. The present series of experiments shows that the injection-to-kindled seizure interval is critically important for the long-term inhibition. We propose that the anticonvulsant effect is caused by an interaction of the cysteamine and the kindled seizure.


Long-term outcome in high-risk corneal transplantation and the influence of HLA-A and HLA-B matching.
To evaluate long-term follow-up of high-risk corneal transplants allocated after matching for broad HLA-A and HLA-B antigens and to establish whether matching for HLA-A and -B antigen "splits" would result in a reduced risk of immunologic graft failure. A total of 303 high risk corneal transplants was included. Class I antigen-matched donor corneas were obtained using broad HLA-A and -B antigen data and accepting 0 or 1 mismatch at each locus. Analysis of HLA antigens was performed also on the split typing level. The influence on immunologic graft failure for an increasing number of matched class I antigens based on split typing was analyzed with Kaplan-Meier statistics and Cox regression. Graft survival and indication for transplantation were investigated. Rejection was the cause of 34% of all graft failures. A significantly higher immune failure free graft survival was found in a group with 0 or 1 HLA-A and -B mismatch based on split typing (log-rank test, P = 0.002). A beneficial effect of matching for split antigens was shown with multivariate analysis (odds ratio, 0.41). One third of graft failures in our high-risk population was caused by irreversible graft rejection. Allocation of donor corneas based on a 0 or 1 split antigen mismatch at both HLA-A and -B loci could contribute to a higher immune failure free graft survival and could result in a higher overall graft survival.


Carbon fixation of CO2 via cyclic reactions with borane in gaseous atmosphere leading to formic acid (and metaboric acid); A potential energy surface (PES) study.
Carbon dioxide (CO2), a stable gaseous species, occupies the troposphere layer of the atmosphere. Following it, the environment gets warmer, and the ecosystem changes as a consequence of disrupting the natural order of our life. Due to this, in the present reasearch, the possibility of carbon fixation of CO2 by using borane was investigated. To conduct this, each of the probable reaction channels between borane and CO2 was investigated to find the fate of this species. The results indicate that among all the channels, the least energetic path for the reaction is reactant complex (RC) to TS (A-1) to Int (A-1) to TS (A-D) to formic acid (and further meta boric acid production from the transformation of boric acid). It shows that use of gaseous borane might lead to controlling these dangerous greenhouse gases which are threatening the present form of life on Earth, our beautiful, fragile home.


A new approach to chemotherapy: drug-induced differentiation kills African trypanosomes.
Human African trypanosomiasis (sleeping sickness) is a neglected tropical disease caused by Trypanosoma brucei spp. The parasites are transmitted by tsetse flies and adapt to their different hosts and environments by undergoing a series of developmental changes. During differentiation, the trypanosome alters its protein coat. Bloodstream form trypanosomes in humans have a coat of variant surface glycoprotein (VSG) that shields them from the immune system. The procyclic form, the first life-cycle stage to develop in the tsetse fly, replaces the VSG coat by procyclins; these proteins do not protect the parasite from lysis by serum components. Our study exploits the parasite-specific process of differentiation from bloodstream to procyclic forms to screen for potential drug candidates. Using transgenic trypanosomes with a reporter gene in a procyclin locus, we established a whole-cell assay for differentiation in a medium-throughput format. We screened 7,495 drug-like compounds and identified 28 hits that induced expression of the reporter and loss of VSG at concentrations in the low micromolar range. Small molecules that induce differentiation to procyclic forms could facilitate studies on the regulation of differentiation as well as serving as scaffolds for medicinal chemistry for new treatments for sleeping sickness.


Field efficacy of an ivermectin jetting fluid for control of the sheep body louse Bovicola (Damalinia) ovis in New Zealand.
The efficacy of an ivermectin jetting fluid against the sheep body louse, Bovicola (Damalinia) ovis, in long-woolled sheep was investigated in three field trials. In all trials, louse populations in hand-jetted sheep were reduced to nondetectable numbers within 2 weeks of treatment. Bv comparison, shorn and unshorn control sheep maintained detectable infestations for the duration of the trials.


Rheumatic tricuspid stenosis without involvement of the mitral valve.
We describe a case of rheumatic tricuspid stenosis without involvement of the mitral valve. Rheumatic disease of the tricuspid valve is very rare in the absence of concomitant mitral valvar disease. We suggest that the closing pressure at the valve is not the only factor governing localization of the rheumatic process.


Injury Risk Is Increased by Changes in Perceived Recovery of Team Sport Players.
The aim of this study is to investigate if changes in perceived stress and recovery over the course of a season are risk factors for acute and overuse injuries. A prospective nonexperimental cohort design. Data were gathered at the SportsFieldLab Groningen and at the facilities of the participating teams. Eighty-six male and female basketball, volleyball, and korfball players aged 21.9 ± 3.5 years. In this 10-month observational study, the independent variables are the changes in perceived stress and recovery. The Recovery-Stress Questionnaire for Athletes (RESTQ-Sport) was filled out every 3 weeks throughout the season to assess changes in perceived stress and recovery. Acute and overuse injuries were registered by the teams' physical therapists. Odds ratios and 95% confidence intervals were calculated. During one season, 66 acute and 62 overuse injuries were registered. Multinomial regression analysis showed that perceived General Recovery, shown in the scales Social Recovery and General Well-Being, decreased in the 6-week period before an acute injury (OR 0.59 and 0.61, respectively, P ≤ 0.05) compared with healthy periods. Risk of overuse injuries increased when perceived Sport Recovery, shown in the Personal Accomplishment scale, decreased in the 3-week period before the injury (OR 0.59, P ≤ 0.05) compared with healthy periods. Therefore, decreased perceived recovery can indicate an increased injury risk. General Recovery affects acute injury risk and Sport Recovery affects the risk of an overuse injury. Monitoring perceived recovery over the course of a season could give guidance for recovery enhancing practices to prevent injuries.


The relationship between subclinical atherosclerosis, non-high-density lipoprotein cholesterol, exercise, and diet among male participants of the PACC Project.
Non-high-density lipoprotein (HDL) cholesterol is recommended as a secondary lipid goal treated initially with lifestyle modification. However, the relationship between non-HDL and subclinical atherosclerosis is unknown. We examined the independent relationships between coronary artery calcium (CAC), lipids including non-HDL, exercise, and diet among healthy male participants of the Prospective Army Coronary Calcium (PACC) Project. Male participants from the PACC Project (n = 1637, mean age 42.8 years; no history of coronary heart disease) were studied. We used validated surveys to measure dietary quality and habitual physical exercise. Fasting lipid concentrations and other cardiovascular risk variables were measured. Subclinical atherosclerosis was detected with the use of electron beam computed tomography for CAC. Factors independently associated with the presence of any detectable CAC (CAC score > 0), including standard CV risk variables, non-HDL, exercise, and diet, were evaluated with the use of logistic regression. The mean Framingham risk score was 4.6 ± 2.6%; CAC was present in 22.4%. Fasting lipid concentrations showed mean LDL-C 128 ± 32 mg/dL, HDL-C 50 ± 13 mg/dL, TG-C 130 ± 86 mg/dL, and non-HDL-C 154 ± 37 mg/dL. Men with CAC had significantly greater levels of LDL-C (135 vs 127 mg/dL), TG (148 vs 124 mg/dL), and non-HDL-C (164 vs 151 mg/dL) and less habitual physical activity (P = 0.006). There were nonsignificant trends between prevalent CAC, greater amounts of dietary fat intake, and lower HDL-C. In successive multivariable logistic regression models for the dependent variable CAC, only non-HDL-C (odds ratio [OR] 1.012 per mg/dL; 95% CI 1.002-1.023; P = .019) and age (OR 1.119 per year; 95% CI 1.063-1.178; P < .001) were independently associated with the presence of CAC, and exercise (OR 0.808; 95% CI 0.703-0.928; P = 0.003) was associated with the absence of CAC. Non-HDL-C and exercise are independently predictive of the presence of subclinical CAC among healthy lower-risk middle-aged men.


Long-Term Outcomes of Surgical Resection of Pathologically Confirmed Isolated Para-Aortic Lymph Node Metastases in Colorectal Cancer: A Systematic Review.
Para-aortic lymph node (PALN) metastases represent patterns of initial recurrence in only 2-6% CRC patients, after an estimated 23-28 month time interval. An increasing trend towards curative surgery has been witnessed in patients presenting with controlled PALN recurrence. Nevertheless, lack of consensus has impaired an unambiguous statement for PALN recurrence resection. We performed a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines, which led us to gain deeper insight into the prognostic factors and long-term outcomes after resection for synchronous or metachronous pathologically confirmed CRC isolated para-aortic lymph node metastases (PALNM). Pubmed/MEDLINE, Embase, Scopus, Cochrane Library and Web of Science databases were used to search all related literature. The nine articles included covered a study period of 30 years (1988-2018), with a total of 161 patients. At presentation, most primary CRCs were located in the colon (74%) and 95.6%, 87.1% and 76.9% patients had T3-T4, N1-N2 and well/moderately differentiated CRC, respectively. We identified a 59.4-68% 3-year OS rate and 53.4-87.5% 5-year OS rate, with a 25-84 months median OS, 26.3-61% 3-year DFS rate and 0-60.5% 5-year DFS rate, with a 14-24 month median DFS. Overall, 62.1% re-recurrence rate ranged from 43.8% to 100%. Although PALNMs resection in CRC patients may be considered a feasible and beneficial option, no conclusions or recommendations can be made taking into account the current evidence. Therefore, further randomized, possibly multicenter trials are strongly recommended and mandatory if we want to have our results confirmed and patient selection criteria clearly identified.