Propylthiouracil-Induced Vasculitis With Alveolar Hemorrhage Confirmed by Clinical, Laboratory, Computed Tomography, and Bronchoscopy Findings: A Case Report and Literature Review.
Propylthiouracil (PTU) is commonly used to treat hyperthyroidism and can induce antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Although this is a rare side effect, ANCA-associated vasculitis can progress to severe disease if its diagnosis and treatment are delayed, leading to a poor prognosis. A 43-year-old woman with Graves' disease developed pulmonary vasculitis and diffuse alveolar hemorrhage (DAH) associated with ANCA against myeloperoxidase and proteinase-3 that was confirmed by computed tomography (CT) and bronchoscopy and treated with PTU. The symptoms and signs of alveolar hemorrhage were rapidly resolved after PTU withdrawal and treatment with corticosteroids. After 6 months of follow-up, the patient maintained complete ANCA-negative clinical remission status, as confirmed by normal CT and bronchoscopy findings. To our knowledge, this is the first documented case of bronchoscopic comparison of PTU-induced DAH before and after steroid treatment. Patients treated with PTU should be closely monitored and followed up, even if the drug has been used for several years. When patients develop progressive dyspnea with alveolar opacities on chest imaging that cannot be explained otherwise, alveolar hemorrhage should be an important differential diagnosis while investigating the case. Early diagnosis and prompt discontinuation of the PTU treatment are essential for improving patient outcomes.


Persistent papules and plaques in systemic juvenile idiopathic arthritis.
A 6-year-old girl presented with nightly fever, persistent joint pain of the knees, ankles, lower back, and hip. Her skin lesions were evanescent salmon-colored patches along with persistent pruritic light to dark pink papules and plaques on her face, post-auricular scalp, trunk, thigh, and bilateral upper extremities. Skin biopsy supported the diagnosis of fixed papules and plaques of systemic juvenile idiopathic arthritis (sJIA). We report this case to highlight diagnostic features of this exceedingly rare cutaneous presentation of sJIA presenting with typical cutaneous salmon-colored evanescent eruptions.


Utility of the New Indian Society of Paediatric and Adolescent Endocrinology (ISPAE) Guidelines for Congenital Hypothyroidism Screening in a High Risk Unit.
To study the new ISPAE guidelines in neonates with congenital hypothyroidism and present authors' experience in managing these neonates. A retrospective review of all babies who were screened for congenital hypothyroidism in the institution over a period of 5 y was conducted. Details pertaining to maternal risk factors, neonatal risk factors, screening TSH, venous TSH and details of etiological evaluation including: ultrasound thyroid, technetium 99m scintigraphy and anti thyroid peroxidase antibody estimation were retrieved. The cases were assessed using the new ISPAE guidelines. During the study period, 8107 babies were screened for congenital hypothyroidism, 83 cases had confirmed disease and 47 had established etiology. There is a fair correlation between screening TSH and venous TSH (r = 0.7, p < 0.05). The estimated incidence of congenital hypothyroidism in present series is 1 in 97 cases. Out of the 83 cases, 36 (43.3%), 16 (19.2%) and 31 (37.3%) cases had screening TSH >20 μIU/mL, 6-20 μIU/mL and < 6 μIU/mL, respectively. Out of the 47 babies with screening TSH <20 μIU/mL, 23 (48.9%), 25 (53.1%) and 12 (25.5%) cases had prematurity, maternal thyroid disease and illness, respectively, as risk factors (some babies had more than one risk factor). Of the 83 cases, all of them had venous TSH >10 μIU/mL and five cases had low Free T4 (<1.1 ng/dl). Thus, none of the cases with congenital hypothyroidism were missed on the new ISPAE guidelines. The new ISPAE guidelines for neonatal screening for congenital hypothyroidism are very useful and applicable in Indian neonates.


[A comparative study of 0.15% sodium hyaluronate versus polyvinyl alcohol in the treatment of dry eyes].
To evaluate the efficacy of two artificial tears for the treatment of dry eyes: 0.15% sodium hyaluronate and polyvinyl alcohol. The study included 60 dry eyes in 30 patients. Fifteen of the patients were treated with 0.15% sodium hyaluronate and 15 with polyvinyl alcohol. Five drops a day for one month was given in both groups. Visual acuity, Schirmer's test, tear clearance, dry eye symptoms questionnaire, fluorescein and rose bengal staining, corneal sensibility, bulbar hyperemia, tear detritus, meibomian gland plug, palpebral erythema and edema before and after treatment were evaluated. Symptoms as judged by the dry eye questionnaire, as well as both fluorescein and rose bengal staining, were significantly improved by 0.15% sodium hyaluronate. The polyvinyl alcohol treated patients did not show a significant improvement in any parameter. Sodium hyaluronate was more effective than polyvinyl alcohol in the treatment of patients with dry eyes (Arch Soc Esp Oftalmol 2005; 80: 387-394).


Taste and acoustic reflex after recovery from facial muscle paralysis in patients with facial nerve palsy.
There are few studies on taste or acoustic reflex (AR) in patients after recovery from facial muscle paralysis (FMP). To investigate the recovery of AR and taste in patients who have recovered from peripheral facial nerve palsy (FNP). The study included 25 patients whose FMP had resolved after treatment for FNP. A difference in taste threshold of ≤4 dB between the affected and unaffected sides in the electric taste test was defined as normal; an AR on the affected side was assessed to be ≥90% of the AR on the unaffected side was defined as normal. Six months after treatment, 8% of patients with FNP who had recovered from FMP still showed taste disorders, and 60% of patients showed abnormal AR. The number of subjects whose electric taste threshold was normal after treatment was significantly higher than the number of subjects whose AR assessment was normal (p < .01). This study demonstrates that even among subjects whose FMP is resolved after treatment for FNP, there are some whose taste and AR do not recover. Physicians should be aware of ear symptoms persisting after facial muscle recovery.


Mesangial function and glomerular sclerosis in rats after unilateral nephrectomy.
To investigate the possible relationship between disturbance of mesangial function and segmental localization of glomerular sclerosis, five uninephrectomized male Wistar rats and five sham-operated controls received colloidal carbon intravenously. At 4 months 8.4 +/- 2.5% of the glomeruli of the nephrectomized rats showed focal sclerosis. Glomeruli of nephrectomized rats contained significantly more carbon than glomeruli of controls. Glomeruli with focal sclerosis contained significantly more carbon than normal glomeruli in the same kidneys with a preferential tracer localization within the lesions. In another experiment carbon injections were given before surgery. At 4 months 12.6 +/- 4.1% of the glomeruli of the nephrectomized rats showed focal sclerosis, an incidence not significantly different from that of the first experiment. Glomerular carbon content was equal in experimental and control rats and no preferential localization of the tracer within the lesions was found. From these results we conclude that the preferential localization of carbon in the glomerular lesions in rats nephrectomized before injection of carbon is caused by the increased delivery of tracer shortly after injection to those glomerular areas where sclerosis will develop at a later time. The development of focal sclerosis may be related to the local deposition of harmful substances from the circulation.


Perinatal Care Preparedness in Kochi Prefecture for When a Nankai Trough Earthquake Occurs: Action Plans and Disaster Liaisons for Pediatrics and Perinatal Medicine.
A Nankai Trough earthquake is highly likely to occur in near future, and perinatal medical resources and care in Kochi Prefecture may be insufficient after such an event. Therefore, we evaluated the medical and public health measures needed to prepare for caring for pregnant women in Kochi Prefecture in the aftermath of such an earthquake and the potential action plans for the prefecture. We estimated that immediately after an earthquake, approximately 30 pregnant women will require urgent medical treatment, most of whom will be in the prefectural capital, Kochi City, and perinatal medical care in Kochi City may be insufficient. Therefore, we used the projected flooding areas to divide Kochi City and its surrounding areas into 3 areas and allocated at least one Disaster Liaison for Pediatrics and Perinatal Medicine (DLPPM) to each disaster base hospital in those 3 areas. In a disaster, the DLPPMs will serve as key individuals in their respective areas and coordinate the allocation of medical care. A DLPPM will be allocated also within the Disaster Medical Response Headquarters of Kochi Prefecture and be responsible for overseeing perinatal care in the whole of Kochi Prefecture. Our study shows that estimating the number of affected pregnant women and requirement for perinatal medical care is an effective way to prepare realistic disaster measures and to enable a specific plan to be formulated for effective allocation and management of DLPPMs. We believe that our system can serve as a model in perinatal disaster medicine.


Breakthrough therapy-designated oncology drugs: are they rightfully criticized?
The US Food and Drug Administration (FDA) has four expedited programs, including the breakthrough therapy designation (BTD). Recently, this program has been criticized. In this feature, we determine whether BTD oncology drugs were truly a breakthrough, based on the outcome of a validated instrument to measure clinical benefit. We find that only a few drugs were likely a breakthrough, indicating that the success rate of the BTD program is somewhat low. Despite this, we believe that programs for fast drug approval do have a place in the current regulatory practice and that the necessary efforts for their improvement should be further explored, especially considering the remaining unmet medical need for patients with cancer.


Mono-allelic loss of YTHDF3 and neurodevelopmental disorder: clinical features of four individuals with 8q12.3 deletions.
The YTH domain family member 3 gene (YTHDF3) encodes a reader of the abundant N6-methyladenosine (m6 A) modification of eukaryotic mRNA, which plays an essential role in regulating mRNA stability and is necessary to achieve normal development of the central nervous system in animal models. YTHDF3 has not previously been implicated in Mendelian disease despite a high probability of loss of function intolerance and statistical evidence of enrichment for gene-disruptive de novo variants in large-scale studies of individuals with intellectual disability and/or developmental delay. We report four individuals with deletion of 8q12.3, deletion size 1.38-2.60 Mb, encompassing YTHDF3, three of them were de novo, and in one case, the inheritance was unknown. Common features of the individuals (age range, 4-22 years) were developmental delay and/or intellectual disability. Two individuals underwent squint surgery. We suggest that haploinsufficiency of YTHDF3 causes a neurodevelopmental disorder with developmental delay and intellectual disability of variable degree.


Combined laparoscopic and percutaneous management of calcified renal hydatid cyst--a novel nephroscope- and lithotripter-assisted technique.
To describe the novel technique of percutaneous nephroscope-assisted renal hydatid cyst evacuation and lithotripter-assisted division of the cyst wall for combined laparoscopic and percutaneous management. A calcified hydatid cyst of the kidney is a rare entity and needs special techniques for total laparoscopic management. A 45-year-old woman was treated successfully for a calcified renal hydatid cyst using the transperitoneal laparoscopic technique. A chlorhexidine gluconate and cetrimide mixture was used as the scolicidal solution to sterilize the cyst. The endocyst and daughter cysts were removed completely under vision, after placement of a single 26F nephroscope through a 10-mm port in the cyst, with grasper and lithotripter suction, using chlorhexidine-cetrimide mixture irrigation. Laparoscopic suction did not work well for the viscous contents. The calcified cyst wall did not yield to electrocautery or piecemeal fragmentation, until weakened by division and fragmentation using the pneumatic lithotripter. Partial cyst wall exicision/marsupialisation was complemented with omentoplasty. No intraoperative or early postoperative complications occurred. The patient recovered well with little pain and was discharged early. This technique, in which the principles of percutaneous nephrolithotomy were applied for a special problem, is the first of its type. Calcified renal hydatid cyst evacuation using the novel nephroscope-assisted retrieval of contents and lithotripter-assisted division of the calcified wall is a safe and feasible technique for total minimally invasive management.


Essential metalloelement chelates facilitate repair of radiation injury.
Treatment with essential metalloelement (Cu, Fe, Mn, and Zn) chelates or combinations of them before and/or after radiation injury is a useful approach to overcoming radiation injury. No other agents are known to increase survival when they are used to treat after irradiation, in a radiorecovery treatment paradigm. These chelates may be useful in facilitating de novo syntheses of essential metalloelement-dependent enzymes required to repair radiation injury. Reports of radioprotection, which involves treatment before irradiation, with calcium-channel blockers, acyl Melatonin homologs, and substituted anilines, which may serve as chelating agents after biochemical modification in vivo, as well as Curcumin, which is a chelating agent, have been included in this review. These inclusions are intended to suggest additional approaches to combination treatments that may be useful in facilitating radiation recovery. These approaches to radioprotection and radiorecovery offer promise in facilitating recovery from radiation-induced injury experienced by patients undergoing radiotherapy for neoplastic disease and by individuals who experience environmental, occupational, or accidental exposure to ultraviolet, x-ray, or gamma-ray radiation. Since there are no existing treatments of radiation-injury intended to facilitate tissue repair, studies of essential metalloelement chelates and combinations of them, as well as combinations of them with existing organic radioprotectants, seem worthwhile.


Oncolytic Viruses and Immune Checkpoint Inhibitors: The "Hot" New Power Couple.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer care and shown remarkable efficacy clinically. This efficacy is, however, limited to subsets of patients with significant infiltration of lymphocytes into the tumour microenvironment. To extend their efficacy to patients who fail to respond or achieve durable responses, it is now becoming evident that complex combinations of immunomodulatory agents may be required to extend efficacy to patients with immunologically "cold" tumours. Oncolytic viruses (OVs) have the capacity to selectively replicate within and kill tumour cells, resulting in the induction of immunogenic cell death and the augmentation of anti-tumour immunity, and have emerged as a promising modality for combination therapy to overcome the limitations seen with ICIs. Pre-clinical and clinical data have demonstrated that OVs can increase immune cell infiltration into the tumour and induce anti-tumour immunity, thus changing a "cold" tumour microenvironment that is commonly associated with poor response to ICIs, to a "hot" microenvironment which can render patients more susceptible to ICIs. Here, we review the major viral vector platforms used in OV clinical trials, their success when used as a monotherapy and when combined with adjuvant ICIs, as well as pre-clinical studies looking at the effectiveness of encoding OVs to deliver ICIs locally to the tumour microenvironment through transgene expression.


The Interaction with Disabled Persons Scale: evidencing construct validity with factor analysis and measurement invariance in Greek-speaking healthcare students.
To explore the construct validity and reliability of the Greek version of the Interaction with Disabled Persons Scale (IDPS) amongst healthcare students. Greek IDPS factors were extracted and confirmed by Analysis of Moment Structures. Measurement invariance for the group of students completing a clinical module with people with disabilities was also evaluated. The scale was distributed twice, 3 weeks apart (test-retest reliability) to sample. Greek IDPS scores amongst students with frequent contact with people with disabilities were compared with those with infrequent contact (discriminant validity). 327 healthcare students (21.25 ± 4.3 years, 118 males) participated. Exploratory factor analysis extracted 6 factors explaining 55.66% of total variance. Confirmatory factor analysis showed a good fit of the model (AGFI = 0.95 > 0.90, RMSEA = 0.07 < 0.08, CFI = 0.95 ≥ 0.90, SRMR = 0.00 < 0.08). An adequate fit for the students completing a clinical practice module was observed. The scale's test-retest reliability and internal consistency were excellent; ICC(2,1)=0.86 (CIs:0.82-0.89) and Cronbach's α = 0.87, respectively. Statistically significant differences between the two student groups were yielded; students with frequent contact with people with disabilities had lower scores (mean difference: -4.5; CI: -6.6 to -2.4), suggesting that they were significantly more comfortable with people with disabilities than the students with infrequent contact. The Greek IDPS provided sufficient validity and reliability evidence for evaluating healthcare students' perceptions and attitudes towards people with disabilities.IMPLICATIONS FOR REHABILITATIONThe Greek IDPS demonstrated sufficient validity and reliability evidence to assess the Greek-speaking healthcare students' perceptions and attitudes towards people with disabilitiesCompleting a clinical module working with people with disabilities is not enough to produce adequately positive attitudes in Greek-speaking undergraduate healthcare students. Therefore, faculties need to organize further actions, such as lectures by people with disabilities, students' role play, and discussions or events in co-operation with people with disabilities.


Rat liver type I iodothyronine deiodinase is not identical to protein disulfide isomerase.
This study was done to test the recent hypothesis (Boado et al. (1988) Biochem. Biophys. Res. Commun. 155, 1297-1304) that type I iodothyronine deiodinase (ID-I) is identical to protein disulfide isomerase (PDI). Autoradiograms of rat liver microsomal proteins, labeled with N-bromoacetyl-[125I]triiodothyronine (BrAc[125I]T3) and separated by SDS-PAGE, show predominantly 2 radioactive bands of Mr 27 and 56 kDa. Substrates and inhibitors of ID-I inhibited labeling of the 27 kDa band but not that of the 56 kDa band. Treatment of microsomes with trypsin abolished labeling of the 27 kDa protein and destroyed the activity of ID-I but did not prevent labeling of the 56 kDa protein. Following treatment of microsomes at pH 8.0-9.5 or with 0.05% deoxycholate (DOC) PDI content and labeling of the 56 kDa protein were strongly diminished but ID-I activity and labeling of the 27 kDa protein were not affected. The latter decreased in parallel after treatment at pH greater than or equal to 10. Rat pancreas microsomes contain high amounts of PDI but show no ID-I activity. Reaction of these microsomes with BrAc[125I]T3 results in extensive labeling of a 56 kDa protein but no labeling of a 27 kDa protein. Pure PDI (Mr 56 kDa) was readily labeled by BrAc[125I]T3 but showed no deiodinase activity. These results strongly suggest that the 27 kDa band represents (a subunit of) ID-I while the 56 kDa band represents PDI. From these and other data it is concluded that PDI and ID-I are not identical proteins.


Electronic effects in iridium C-H borylations: insights from unencumbered substrates and variation of boryl ligand substituents.
Experiment and theory favour a model of C-H borylation where significant proton transfer character exists in the transition state.


Waveguides in medical ultrasonics.
Propagation of ultrasound in a number of thin solid elastic waveguides is described from the Pochhammer theory. The waveguides discussed have radii equal to the radii of stylets of the most frequently used biopsy needles. The group velocities of the modes and the form of the particle amplitudes of the lowest longitudinal and flexural modes in each of the styles at a frequency of 3.5 MHz are presented.


Targeted Workup after Initial Febrile Urinary Tract Infection: Using a Novel Machine Learning Model to Identify Children Most Likely to Benefit from Voiding Cystourethrogram.
Significant debate persists regarding the appropriate workup in children with an initial urinary tract infection. Greatly preferable to all or none approaches in the current guideline would be a model to identify children at highest risk for a recurrent urinary tract infection plus vesicoureteral reflux to allow for targeted voiding cystourethrogram while children at low risk could be observed. We sought to develop a model to predict the probability of recurrent urinary tract infection associated vesicoureteral reflux in children after an initial urinary tract infection. We included subjects from the RIVUR (Randomized Intervention for Children with Vesico-Ureteral Reflux) and CUTIE (Careful Urinary Tract Infection Evaluation) trials in our study, excluding the prophylaxis treatment arm of the RIVUR. The main outcome was defined as recurrent urinary tract infection associated vesicoureteral reflux. Missing data were imputed using optimal tree imputation. Data were split into training, validation and testing sets. Machine learning algorithm hyperparameters were tuned by the validation set with fivefold cross-validation. A total of 500 subjects, including 305 from the RIVUR and 195 from the CUTIE trials, were included in study. Of the subjects 90% were female and mean ± SD age was 21 ± 19 months. A recurrent urinary tract infection developed in 72 patients, of whom 53 also had vesicoureteral reflux (10.6% of the total). The final model included age, sex, race, weight, the systolic blood pressure percentile, dysuria, the urine albumin-to-creatinine ratio, prior antibiotic exposure and current medication. The model predicted recurrent urinary tract infection associated vesicoureteral reflux with an AUC of 0.761 (95% CI 0.714-0.808) in the testing set. Our predictive model using a novel machine learning algorithm provided promising performance to facilitate individualized treatment of children with an initial urinary tract infection and identify those most likely to benefit from voiding cystourethrogram after the initial urinary tract infection. This would allow for more selective application of this test, increasing the yield while also minimizing overuse.


Synthesis and biological evaluation of novel benzoxazinyl-oxazolidinones as potential antibacterial agents.
A number of benzoxazinyl-oxazolidinones bearing 3-trizolylmethyl or 3-carboxamide side chain were designed and synthesized with the aim to develop antibacterial agents with improved properties. In vitro antibacterial activities of these novel compounds were evaluated against a panel of resistant and susceptible Gram-positive bacteria. Most analogues bearing 3-trizolylmethyl showed good to moderate antibacterial activities. Compound 12a exhibited a fourfold increase in activity compared with linezolid against all the tested strains, which was identified to be a promising antibacterial agent for further evaluation.


Expansion of the Kell blood group system: two new high-prevalence antigens and two novel K0 (Kellnull ) phenotypes.
The number of KEL alleles associated with new antigens or loss of expression of high-prevalence antigens continues to increase. We investigated KEL in five samples: two with K0 (null) phenotypes and three with normal Kell expression and antibodies to high-prevalence antigens. Red blood cell (RBC) typing and antibody identification were by standard methods. Genomic DNA was isolated from white blood cells and DNA array testing and sequencing of KEL exons was performed by standard methods. Proband 1, an Asian woman with Kp(b+) RBCs, presented with alloanti-Kp(b) . Four years later, the antibody was reactive with all RBCs except K0 . She was homozygous for KEL c.877C>T change (p.Arg293Trp), and the high-prevalence antigen absent from her RBCs was named KHUL. Probands 2 and 3, both Japanese and homozygous for KEL c.875G>A (p.Arg292Gln), presented with an antibody reactive with all except K0 RBCs. The antibody, named KYOR, recognizes an antigen antithetical to KYO (KEL31). Proband 4, a pregnant Middle Eastern woman, presented with alloanti-Kp(b) , but her RBCs did not express Kell antigens. She was homozygous for KEL c.230G>T (p.Cys77Phe). Proband 5, a multiply transfused Caucasian female with an antibody reactive with all RBCs except K0 and lacking Kell antigens, was a compound heterozygote carrying a silenced allele c.574C>T (p.Arg192Stop) in trans to c.1664G>A (p.Gly555Glu). We describe two new high-prevalence Kell antigens, KHUL (ISBT 006037; KEL37) and KYOR (ISBT 006038; KEL38), and two novel alleles encoding K0 phenotypes. We caution that antibodies produced by individuals with K0 RBCs or lacking high-prevalence antigens can present as anti-Kp(b) .


Transcriptome analysis reveals genes related to the synthesis and metabolism of cell wall polysaccharides in goji berry (Lycium barbarum L.) from various regions.
In goji berries (Lycium barbarum L.), the cell wall properties and ripening environment affect fruit quality and their economic benefits. However, the mechanism underlying the cell wall remains to be fully elucidated. The results showed that total sugar content was higher in Qinghai berries (13.87%, P < 0.01), whereas cellulose content peaked in Zhongning berries (28%, P < 0.05). Arabinose, galactose, and galacturonic acid were the principal components of the cell wall polysaccharides in goji berries. Among them, the content of galactose in Zhongning was significantly the highest (P < 0.05). Interestingly, we found that highly expressed β-glucosidase and lowly expressed endoglucanase led to cellulose accumulation by RNA-sequencing analysis. The expression analysis results suggested that pectate lyase and pectinesterase enzymes could be major factors related to higher galactose and galacturonic acid contents in Zhongning compared to in Qinghai and Gansu. The starch and sucrose metabolism pathway, pentose and glucuronate interconversions pathway, and galactose metabolism pathway played a significant role in cell wall polysaccharide synthesis and metabolism. In the present study, we aimed to provide some insights into the cell wall on polysaccharide composition, structural features, and gene analysis in goji berries from Zhongning, Qinghai, and Gansu in China. These results might help to clarify the molecular function of the major genes in the cell wall polysaccharides of goji berries and provide a solid foundation for further study. © 2023 Society of Chemical Industry.


Using a generalized neural network to identify airway obstructions in anesthetized patients postoperatively based on photoplethysmography.
Photoplethysmography has been recently studied asa non-invasive indicator of circulatory and respiratory function. In this study, photoplethysmographic (PPG) data were recorded from patients under the influence of anesthesia, but not intubated. Both time and frequency domain features were extracted from the PPG and used as inputs to a neural network classifier. This classifier considers inter-subject variability so that it generalizes well to a large population. This classifier provided 86.1%accuracy to classify segments as being times of 'obstructed' vs.'normal' airways status.


Comparison of in vitro and in vivo binding site competition of Bacillus thuringiensis Cry1 proteins in two important maize pests.
Binding site models, derived from in vitro competition binding studies, have been widely used for predicting potential cross-resistance among insecticidal proteins from Bacillus thuringiensis. However, because discrepancies have been found between binding data and observed cross-resistance patterns in some insect species, new tools are required to study the functional relevance of the shared binding sites. Here, an in vivo approach has been applied to the competition studies to establish the functional relevance of shared binding sites as determined by in vitro competition assays. Using Cry disabled proteins as competitors in mixed protein overlay assays, we assessed the preference of Cry1Ab, Cry1Fa, and Cry1A.105 proteins for shared binding sites in vivo in two important corn pests, Ostrinia nubilalis and Spodoptera frugiperda. This study shows that in vivo and in vitro binding site competition assays can provide useful information to better ascertain whether different Cry proteins share binding sites and, consequently, whether cross-resistance due to binding site alteration can occur. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Misoprostol and estradiol to enhance visualization of the transformation zone during cervical cancer screening: An integrative review.
The purpose of this integrative literature review was to appraise studies conducted worldwide using misoprostol and estradiol in converting Type 3 transformation zone (TZ) of the cervix into Types 1 or 2 and to assess which regimen could be more feasible in low-and-middle-income countries (LMICs). We reviewed the English language literature for peer-reviewed studies that evaluated strategies to convert Type 3 TZs to Types 1 or 2 for cervical cancer screening. Web of Science and PubMed searches were performed up to July 2020. Search terms included: "cervical colposcopy," "inadequate colposcopy", "cervical cancer screening", "transformation zone," "estrogen", "estradiol", and "misoprostol." Inclusion criteria were articles published in the English language, original research, and peer reviewed articles. A total of 127 articles were abstracted, 24 articles were reviewed, and 9 articles met all inclusion criteria. We found that intravaginal misoprostol, intravaginal estradiol, and oral estradiol can successfully convert Type 3 TZ to Types 1 or 2. A single dose of vaginal misoprostol had a similar maximum response rate (20-80%) to a multi-dose regimen over several days or weeks of both intravaginal estradiol (64-83%) and oral estradiol (50-70%). Misoprostol administration was associated with more side effects such as abdominal cramping and vaginal bleeding compared to estradiol, although these were generally mild. In conclusion, Oral estradiol, intravaginal estradiol, and intravaginal misoprostol can be used to convert Type 3 TZ to Types 1 or 2. Intravaginal misoprostol is well tolerated and more feasible in LMICs due to availability and shorter treatment schedule compared to oral or intravaginal estradiol.


Advocacy for Anesthesiologists.
Advocating for anesthesiology is a professional responsibility. We need to make the public aware of the role we play in assuring their safety and comfort; and we must also ensure that payment models are fair and commensurate with the quality of our work.


Fluorescence polarization modulation super-resolution imaging provides refined dynamics orientation processes in biological samples.
Combining polarization modulation Fourier analysis and spatial information in a joint reconstruction algorithm for polarization-resolved fluorescence imaging provides not only a gain in spatial resolution but also a sensitive readout of anisotropy in cell samples.


Aphthoid ulcers in Crohn's colitis.
Aphthoid ulceration is a strong indication and the earliest radiographic sign of Crohn's colitis. These small discrete ulcers were found by double contrast barium enema examination in 40 out of 91 patients with Crohn's colitis. Seen en face each ulcer appears as a central fleck of barium surrounded by a translucent halo set amidst a patch of normal mucosa. Their detection gives a more accurate assessment of the extent of disease. This information is required in order to plan medical or surgical treatment and can only be provided by meticulous double contrast examination or colonoscopy. Aphthoid ulceration has been demonstrated prior to the onset of bowel symptoms, and several years before the advent of severe colonic disease. The appearance of aphthoid ulcers in established quiescent disease has been observed to herald a relapse. The radiographic demonstration of the evolution of ulceration, which is illustrated, closely reflects what is seen on macroscopic examination of excised specimens and explains the characteristic patchiness and discontinuity of disease.


Biological Control of Water Hyacinth Under Conditions of Maintenance Management: Can Herbicides and Insects Be Integrated?
/ We hypothesized that repeated herbicidal (maintenance) control of water hyacinth infestations in Florida suppressed biological control agent populations, especially the weevils Neochetina eichhorniae and N. bruchi. We therefore sampled water hyacinth and weevil populations at 54 sites distributed statewide. Half were under maintenance control, half were not treated with herbicides. General site conditions were assessed, demographic data were collected on weevil and plant populations, the reproductive condition of the weevils was determined, and plant nutrient and proximate composition of water hyacinth leaves were analyzed. Water hyacinth infestations under maintenance control were minimal when compared to unmanaged sites. Likewise, on a population basis, all weevil cohorts were much lower due to the paucity of plants. Plants at unmanaged sites, where weevil intensities were much higher, suffered high levels of stress and showed low growth potential. Lower percentages of the female weevils were reproductive at unmanaged sites when compared to managed sites, so densities of reproductives and immatures were similar at both site types. Reproductive status of the weevils improved with increased plant quality. Plant quality, in turn, declined as stresses arising from weevil feeding increased. Plant quality was positively correlated with plant growth potential and flower production. Thus, maintenance control improved plant nutritive quality thereby inducing reproductive vigor of the weevils, but ensuring plant regrowth and the need for future control. This suggests that biological and herbicidal controls should be integrated, using herbicides to maintain water hyacinth infestations below management thresholds but in a manner that conserves biological control agent populations. This approach would lead to improved plant nutritional quality that would, in turn, stimulate reproduction in biological control agent populations. KEY WORDS: Eichhornia crassipes; Neochetina eichhorniae; Neochetina bruchi; Phytophagy; Integrated control; Aquatic weeds


Estimation of magnetic particle clustering in magnetic fluids from static magnetization experiments.
The volume fraction dependence of the static magnetization of two magnetic fluids with different degrees of steric stabilization was measured at low field values (0-10 kA/m) and it was found to be nonlinear for both magnetic fluids. The nonlinearity is more pronounced in the case of the less stabilized magnetic fluid. The experimental data were processed by nonlinear regression using an analytical model for the formation of chain-like magnetic particle aggregates in magnetic fluids. The calculated dependence on the degree of steric stabilization, magnetic field, and sample concentration of the mean number of particles per chain was in the range (1-1.04).


Ribosomal protein P2: a potential molecular target for antisense therapy of human malignancies.
Ribosomal protein P2 is an important component of protein translation machinery. We hypothesized that antisense-mediated depletion may disrupt the proteome of cancer cells. This study includes experiments to ascertain whether this could be a useful approach for cancer therapies. MIA PaCa-2 and BxPC-3 cells were transfected with P2-antisense oligonucleotide or controls. Growth was assayed using MTT. Protein P2 was measured using Western blotting. Proteomes were compared using two-dimensional electrophoresis and changes were characterized by mass spectrometry. A macroarray was used to identify cancers which may be vulnerable. Antisense-P2 reduced P2 levels by 63% (p < 0.05) and inhibited BxPC-3 growth to 65% of control (p < 0.05). Seventeen (5.4%) proteins changed on two-dimensional electrophoresis including Rho C, translationally-controlled tumor protein, vinculin, LDH, ribosomal protein L23a, F-actin capping protein and eIF-3. Breast cancer underexpressed P2 compared to normal tissue (p < 0.001). Antisense-P2 technology has potential to slow growth of cancer cells. This effect is mediated through multiple proteomic changes.


Unexpected High Intragenomic Variation in Two of Three Major Pest Thrips Species Does Not Affect Ribosomal Internal Transcribed Spacer 2 (ITS2) Utility for Thrips Identification.
The mitochondrial cytochrome oxidase I gene (mtCO1) and the ribosomal internal transcribed spacer 2 region (ITS2) are among the most widely used molecular markers for insect taxonomic characterization. Three economically important species of thrips, Scirtothripsdorsalis, Thripspalmi, and Frankliniellaoccidentalis were selected to examine the extent of intragenomic variation within these two marker regions in the family Thripidae, and determine if this variation would affect the utility of markers in thrips molecular diagnostics. For each species, intragenomic (within individual) variation and intergenomic (among individuals) variation was assessed by cloning and sequencing PCR-amplified copies. Intergenomic variation was generally higher than intragenomic variation except in cases where intergenomic variation was very low, as in mtCO1 from S.dorsalis and F.occidentalis. Intragenomic variation was detected in both markers in all three of the thrips species, however, 2-3 times more intragenomic variation was observed for ITS2 than mtCO1 in both S.dorsalis and T.palmi. Furthermore, levels of intragenomic variation were low for both of the genes in F.occidentalis. In all of the three thrips species, no sex-based clustering of haplotypes was observed in either marker. Unexpected high intragenomic variation in ITS2 for two of three thrips species did not interfere with thrips diagnostics. However, caution should be taken in applying ITS2 to certain studies of S.dorsalis and T.palmi when high levels of intragenomic variation could be problematic or confounding. In such studies, mtCO1 may be a preferable marker. Possible reasons for discrepancies in intragenomic variation among genomic regions are discussed.


The pathway of secretion of proteinases in Trichomonas vaginalis.
Trichomonads secrete large amounts of hydrolytic enzymes into liquid growth medium. Proteinase release by Trichomonas vaginalis has been quantified after resuspension of the parasite in a simple buffered maltose medium. After 6 h incubation, 70-90% of each of two cysteine proteinase activities, one towards benzyloxycarbonyl-arginyl-arginine 4-nitroanilide (Z-RR-Nan) and the other active towards N-benzoyl-prolyl-phenylalanyl-arginine 4-nitroanilide (Bz-PFR-Nan), was extracellular. This release was insensitive to changes in pH within the range from 5.5 to 8.6 but was partially inhibited by chloride ions. The secretion of activity towards Bz-PFR-Nan was temperature-sensitive but was still detectable down to 14 degrees C. Neither this nor other cysteine proteinase activities were detectable on the surface of parasites. Release was stimulated by various amines and monensin, suggesting that secretion was from or via acidic compartments. The intracellular activity towards Bz-PFR-Nan could be totally and irreversibly inhibited by treating the parasites with benzyloxycarbonyl-phenylalanyl-alanine diazomethylketone (Z-FA-DMK), without otherwise harming the cells. Regeneration and routing of the proteinases responsible for this activity was followed after removal of the inhibitor. There was a significant rise in the intracellular level of activity before it became detectable in the medium. The release of this activity was accelerated by amines and monensin, but the build-up of enzyme activity within cells was not prevented. Organelles containing cysteine proteinases banded as a single peak in Percoll density gradients. The density of these increased when cells were treated with dextran. The activity towards Bz-PFR-Nan which reappeared after Z-FA-DMK treatment has a similar distribution. The proteinase-containing fraction could be distinguished from an early (5 min) endosome fraction, suggesting that it was composed of late endosomes/lysosomes. Thus these results imply that the secretion pathway for proteinases necessarily involves lysosomes/late endosomes.


Conventional Radiology in Rheumatoid Arthritis.
In clinical practice, the conventional radiography is still the radiologic method for the diagnosis of rheumatoid arthritis (RA). Moreover, it provides a quick overview of the symptomatic joints to narrow the differential diagnosis and to evaluate progression. RA is a polyarticular disease with bilateral and symmetric involvement of the peripheral joints, especially small joints, and less frequently, the cervical spine. The radiologic features are soft tissue swelling, periarticular osteoporosis, erosions, loss of joint space, and in advanced disease, osteolysis and typical subluxations or deformities, such as ulnar deviation.


Synchronous oral paracoccidioidomycosis and esophageal carcinoma.
Paracoccidioidomycosis is the most common deep mycosis in South America and is caused by Paracoccidioides brasiliensis (P. brasiliensis), a thermally dimorphic fungus. Infections usually occur by inhalation of conidia, which more often cause respiratory, mucocutaneous, and lymph nodal changes. Chronic features of this mycosis can mimic diverse infections and malignancies and constitute diagnosis challenges. Squamous cell carcinoma deserves special attention in this setting. We describe the case of a patient with synchronous diagnosis of oral paracoccidioidomycosis and esophageal squamous cell carcinoma. Concomitance of these conditions may be a casual event, but a not fully understood causal relationship can be involved.


A complex and demanding situation - Midwifery preceptors and midwifery students' experiences of teaching and learning prevention of severe perineal trauma.
Many high-income countries have seen an increase in severe perineal trauma. Teaching strategies and conditions for learning during the active second stage of labour are scarcely described. To describe midwifery preceptors and midwifery students' experiences' of teaching and learning how to manage the second stage of labour, with the specific aim of preventing severe perineal trauma. A qualitative study with focus group discussions and individual in depth-interviews with preceptor midwives (n = 23) and student midwives (n = 10). Data were analysed by qualitative content analysis. "A complex and demanding situation with mutual need for feedback, reflection and safety" was the overall theme describing the conditions. Three sub-themes were identified. "Adapting to a unique situation" refers to the difficulty of teaching and learning the aspects needed to prevent severe perineal trauma, and to provide care during this stage. "Hindering and limiting circumstances" describes teaching strategies that were perceived negatively, and how midwifery students tried to adapt to the preceptors rather than the birthing women. "A trustful and communicative relationship" describes the importance of the relationship between the student and the preceptor, where communication was a central, but not obvious part. An increased awareness among preceptors is needed to optimize teaching strategies, enabling the students to focus on learning the art of the second stage of labour; supporting the woman, preventing severe perineal trauma and ensuring the safety of the unborn baby. Future research should address how existing prevention models can include training to increase preceptors' confidence in teaching.


Properties of the protein kinase that phosphorylates prothymosin alpha.
The prothymosin alpha kinase (ProTalphaK) is an apparently novel enzyme that is responsible for the phosphorylation of prothymosin alpha (ProTalpha), involved in the proliferation of mammalian cells. The present study investigated the properties of this enzyme. ProTalphaK is more effectively activated by Mn2+ than by other divalent cations, and its activity is unaffected by RNA. Its principal substrate in proliferating cells appears to be ProTalpha. Both in vivo and in vitro, it is unable to phosphorylate the peptides thymosin alphaI and thymosin alphaII, derived from the amino terminus of ProTalpha, despite the fact that the sites of phosphorylation of ProTalpha are contained within this part of its sequence. In trials in vivo, inhibition of gene expression abolished both phosphorylation of ProTalpha and ProTalphaK activity. ProTalphaK is located in the cytosolic fractions throughout the cell cycle. Its activity, which is dependent on cell proliferation, increases markedly during S phase and begins to decline as the cell enters G2. Studies of the effects of activators and inhibitors of protein kinases involved in signal transduction pathways suggest that ProTalphaK is activated by phosphorylation in a mitogen-initiated pathway that is dependent on PKC; however, PKC does not itself phosphorylate ProTalphaK, which is therefore presumably phosphorylated by another kinase.


Operative treatment of anterior heterotopic bone formation of the elbow in a patient with severe haemophilia A.
There is no statistical data on the incidence of heterotopic ossification among patients with haemophilia, and a few reports documenting this entity in haemophilia are available. Although post-traumatic heterotopic ossification about the elbow is a well-recognized complication, we are not aware of any previously reported case in haemophiliacs. An 8-year-old boy with severe haemophilia A presented with fixed elbow in 80 degrees of flexion. Radiographs disclosed a mature anterior heterotopic ossification in the form of complete ulnohumeral bony bridge. Surgical excision of the heterotopic bone was performed. A full elbow range of motion was obtained after long-term physiotherapy. We conclude that this surgery is safe and successful in haemophilic patients, if performed at the right time under optimal situation.


Affinity chromatography of lactate dehydrogenase and wheat germ lectin on new gels bearing carboxylic functions.
The suitability of two new functionalized copolymer gels for use in affinity chromatography has been examined. Both gels were substituted by two ligands, one being specific for lactate dehydrogenase and the other for wheat germ lectin. The derivatives thus obtained were used successfully for the purification of two proteins with different biological activities.


The value of Tzanck smear test in diagnosis of erosive, vesicular, bullous, and pustular skin lesions.
Tzanck smear is generally used for the diagnosis of the pemphigus group of autoimmune bullous diseases and mucocutaneous herpesvirus infections. There are only a few studies in the literature investigating its diagnostic value. We aimed to investigate Tzanck smear findings and to determine the diagnostic value of this test in moist (erosive, vesicular, bullous, and pustular) skin lesions. We also aimed to develop an algorithmic approach for the diagnosis of these types of skin lesions according to the Tzanck smear findings. Samples were stained with May-Grünwald-Giemsa and evaluated by the same dermatologist. In some patients, methylene blue and Gram staining or direct immunofluorescence examinations were additionally performed. In all of the study cases, after the evaluation of clinical and laboratory findings (including, when appropriate, potassium hydroxide examination; viral serology; bacterial and fungal cultures; histopathology; direct and indirect immunofluorescence; patch testing), the definite diagnosis was established. We also determined the sensitivity and the specificity of certain Tzanck smear findings. Tzanck smear was performed in a total of 400 patients with moist skin lesions. The sensitivities of multinucleated giant cells and acantholytic cells in herpetic infections, dyskeratotic acantholytic cells and cocci in bullous impetigo, pseudohyphae in candidiasis, acantholytic cells in pemphigus and more than 10 tadpole cells (magnification x100) in spongiotic dermatitis were 84.7%, 92%, 100%, 100%, and 81.5%, respectively. Because Tzanck smears were evaluated by the same dermatologist, no comment could be made regarding the interobserver reliability of this test and how the level of experience with this technique might affect the results. Also, the sensitivity and the specificity of Tzanck smear test findings for certain diseases could not be calculated because of an insufficient number of patients. The Tzanck smear test is an inexpensive, useful, and an easy diagnostic tool for certain skin diseases.


Influence of the conditions of growth on the chemical composition and activity of the enzymes of the cell envelope of the yeast Candida tropicalis IBFM-303.
The article is devoted to a study of the changes in the activity and chemical composition of the enzymes of the cell envelope of the yeast Candida tropicalis IBFM-303 during growth on n-alkanes and glucose, as well as the transport of n-alkanes through the cell membrane and the redistribution of the cell contents in the process of budding on the indicated carbon sources.


Topical nitrogen mustard in the treatment of alopecia areata: a bilateral comparison study.
Topical nitrogen mustard is an alkylating agent. Its efficacy in treating alopecia areata was reported in an uncontrolled study. We present a preliminary, half-head, controlled 16-week study showing that topical nitrogen mustard was of benefit in 1 of 6 patients treated with 50% to 100% scalp involvement. Another 4 patients did not complete the trial.


Commercial airline travel decreases oxygen saturation in children.
To investigate the degree of oxygen saturation decline occurring in children during prolonged commercial air travel. Oxygen saturation and heart rate were measured with a pulse oximeter in healthy pediatric passengers at sea level before boarding a commercial aircraft. These measurements were repeated after 3 hours and 7 hours of flight. Cabin pressure, true altitude, and cabin fraction of inspired oxygen (FiO2) were also recorded at 3 hours and 7 hours. Eighty healthy children (43 boys) aged 6 months to 14 years were studied during eight flights between Honolulu, Hawaii, and Taipei, Taiwan. Oxygen saturation declined, and heart rate increased after 3 hours (95.7%, 105 beats per minute [BPM]) and 7 hours (94.4%, 108 BPM) of flight compared to preflight levels at sea level (98.5%, 100 BPM) (P < 0.001). The 3-hour to 7-hour oxygen saturation and heart rate means differed significantly (P < 0.001, P = 0.014, respectively). The significant drop in oxygen saturation was associated with the decreased cabin partial pressure of oxygen (PO2)--PO2 was 159 mm Hg at sea level, 126 mm Hg after 3 hours, and 124 mm Hg after 7 hours--but the 3-hour and 7-hour difference suggests that flight duration may also contribute to worsened oxygen desaturation. Oxygen saturation declines significantly during commercial airline travel with reduced aircraft cabin pressure and concomitant reduced cabin PO2. We did not observe an "acclimation" of oxygenation as the length of travel increased; rather, the oxygen saturation decline worsened, although it may be partially a result of the lower cabin PO2. Although there were no clinically noticeable ill effects at the level of oxygen saturation decline in these relatively healthy passengers, patients with preexisting anemia or cardiopulmonary disease are likely to experience greater degrees of clinical compromise with similar degrees of oxygen saturation decline.


Brain metastases from lung cancer with neuropsychiatric symptoms as the first symptoms.
To investigate the neuropsychiatric symptoms and their treatment and outcomes in lung cancer patients with brain metastases (BM), with an attempt to achieve early detection and prompt management of these symptoms. Ten lung cancer patients (8 males and 2 females) with BMs who were treated in our center from 2013 to 2019 were enrolled in this analysis. Without exception, all 10 patients presented with chief complaints of neuropsychiatric symptoms, and BMs were eventually diagnosed. Appropriate treatments were offered, and all patients were followed up. Two patients died (case 5 died of sudden massive hemoptysis, and case 6 died after his families refused to receive the invasive treatment). Data on 3- and 5-year survival have been obtained from one patient each. The average follow-up duration was 19.4 months (except that two patients were hospitalized only once, and one patient received the second follow-up visit only 9 days after the first visit). The possibility of BM from lung cancer should be considered when a lung cancer patient develops neuropsychiatric symptoms, and timely diagnosis treatment should be arranged accordingly.


Multi-drug versus single agent chemotherapy for high grade astrocytoma; results of a meta-analysis.
The addition of chemotherapy to postoperative radiation therapy in the treatment of high grade astrocytoma results in a modest increase in 12 and 24 month survival. It is, at present, unclear whether single agent or combination drug therapy constitutes the best drug regimen for these patients. Despite this uncertainty, multi-drug regimens have become standard therapy for some high grade astrocytomas. One year survival data derived from over 2,100 patients enrolled in 9 randomized clinical trials were analyzed using the meta-analytic techniques previously described by Peto et al. This analysis compared the proportion of patients surviving one year treated with multi-drug regimens versus single agent treatment (usually BCNU). All patients included in this analysis also underwent surgery and radiation therapy as part of their clinical management. A summary odds ratio was calculated following a statistical analysis showing a lack of heterogeneity among the included studies in terms of their estimate of effect. The calculated Peto odds ratio was 1.22 with a 95% confidence interval of 0.99-1.36. These data indicate that combination drug treatment is associated with an approximately 22% decreased 1 year survival as compared with single agent therapy. This analysis suggests that the available data do not support the use of combination chemotherapy regimens in this patient population. Additional randomized clinical trials are needed to clearly determine whether any multidrug treatment scheme is superior to currently available single agent therapies.


A Trim-RBD-GEM vaccine candidate protects mice from SARS-CoV-2.
The SARS-CoV-2 pandemic has continued for about three years since emerging in late December 2019, resulting in millions of deaths. Therefore, there is an urgent need to develop a safe and effective vaccine to control SARS-CoV-2. In this study, we developed a bacterium-like particle vaccine that displays the SARS-CoV-2 receptor binding domain (RBD) (named Trim-RBD-GEM) using the GEM-PA system. We evaluated the immunogenicity and protective efficacy of the Trim-RBD-GEM vaccine with the oil-in-water adjuvant AddaVax in C57BL/6 N mice intramuscularly. We found that Trim-RBD-GEM&AddaVax induced high levels of humoral immunity in C57BL/6 N mice. Additionally, the lung virus loads in the immunized group were significantly decreased compared to the adjuvant control and mock groups. Therefore, this vaccine provides protection against lethal infection in a C57BL/6 N mouse model. Our Trim-RBD-GEM&AddaVax vaccine is potentially a promising, rapid, and safe subunit vaccine for preventing and controlling SARS-CoV-2.


Fibromatosis of the cervical fascia.
Fibromatosis is a rare benign soft-tissue tumor of fibroblastic origin arising from the aponeurotic structures. Preoperative diagnosis of fibromatosis of the deep cervical fascia is difficult from clinical presentation alone. We report a case of a tumor of the cervical fascia space for which the radiologic appearance did not exhibit specific characteristics. Critical analysis of the radiologic images combined with fine-needle aspiration findings were helpful in suggesting preoperatively the diagnosis of fibromatosis, which was confirmed histologically after surgical resection.


Gene-based partial least-squares approaches for detecting rare variant associations with complex traits.
Genome-wide association studies are largely based on single-nucleotide polymorphisms and rest on the common disease/common variants (single-nucleotide polymorphisms) hypothesis. However, it has been argued in the last few years and is well accepted now that rare variants are valuable for studying common diseases. Although current genome-wide association studies have successfully discovered many genetic variants that are associated with common diseases, detecting associated rare variants remains a great challenge. Here, we propose two partial least-squares approaches to aggregate the signals of many single-nucleotide polymorphisms (SNPs) within a gene to reveal possible genetic effects related to rare variants. The availability of the 1000 Genomes Project offers us the opportunity to evaluate the effectiveness of these two gene-based approaches. Compared to results from a SNP-based analysis, the proposed methods were able to identify some (rare) SNPs that were missed by the SNP-based analysis.


Therapeutic tools for oral candidiasis: Current and new antifungal drugs.
Candidiasis is one of the most common opportunistic oral infections that presents different acute and chronic clinical presentations with diverse diagnostic and therapeutic approaches. The present study carries out a bibliographic review on the therapeutic tools available against oral candidiasis and their usefulness in each clinical situation. Recent studies on treatment of oral candidiasis were retrieved from PubMed and Cochrane Library. Nystatin and miconazole are the most commonly used topical antifungal drugs. Both antifungal drugs are very effective but need a long time of use to eradicate the infection. The pharmacological presentations of miconazole are more comfortable for patients but this drug may interact with other drugs and this fact should be assessed before use. Other topical alternatives for oral candidiasis, such as amphotericin B or clotrimazole, are not available in many countries. Oral fluconazole is effective in treating oral candidiasis that does not respond to topical treatment. Other systemic treatment alternatives, oral or intravenous, less used are itraconazole, voriconazole or posaconazole. Available novelties include echinocandins (anidulafungin, caspofungin) and isavuconazole. Echinocandins can only be used intravenously. Isavuconazole is available for oral and intravenous use. Other hopeful alternatives are new drugs, such as ibrexafungerp, or the use of antibodies, cytokines and antimicrobial peptides. Nystatin, miconazole, and fluconazole are very effective for treating oral candidiasis. There are systemic alternatives for treating recalcitrant infections, such as the new triazoles, echinocandins, or lipidic presentations of amphotericin B.


Variation of the by-product spectrum during α-ketoglutaric acid production from raw glycerol by overexpression of fumarase and pyruvate carboxylase genes in Yarrowia lipolytica.
The yeast Yarrowia lipolytica secretes high amounts of various organic acids, like citric, isocitric, pyruvic (PA), and α-ketoglutaric (KGA) acids, triggered by growth limitation and excess of carbon source. This is leading to an increased interest in this non-conventional yeast for biotechnological applications. To improve the KGA production by Y. lipolytica for an industrial application, it is necessary to reduce the amounts of by-products, e.g., fumarate (FU) and PA, because production of by-products is a main disadvantage of the KGA production by this yeast. We have examined whether the concentration of secreted organic acids (main product KGA and PA as major by-product and FU, malate (MA), and succinate (SU) as minor by-products) can be influenced by a gene-dose-dependent overexpression of fumarase (FUM) or pyruvate carboxylase (PYC) genes under KGA production conditions. Recombinant Y. lipolytica strains were constructed, which harbor multiple copies of the respective FUM1, PYC1 or FUM1, and PYC1 genes. Overexpression of the genes FUM1 and PYC1 resulted in strongly increased specific enzyme activities during cultivation of these strains on raw glycerol as carbon source in bioreactors. The recombinant Y. lipolytica strains showed different product selectivity of the secreted organic acids KGA, PA, FU, MA, and SU. Concentrations of the by-products FU, MA, SU, and PA decreased significantly at overproduction of FUM and increased at overproduction of PYC and also of FUM and PYC simultaneously. In contrast, the production of KGA with the multicopy strains H355A(FUM1) and H355A(FUM1-PYC1) was comparable with the wild-type strain H355 or slightly lower in case of H355(PYC1). KGA productivity was not changed significantly compared with strain H355 whereas product selectivity of the main product KGA was increased in H355A(FUM1).


Analysis of lncRNAs and mRNA Expression in the ZBTB1 Knockout Monoclonal EL4 Cell Line and Combined Analysis With miRNAs and circRNAs.
In previous experiments, we identified the effect of deletion of the Zbtb1 gene on circRNAs and microRNAs. In this study, we examined the expression profiles of lncRNAs and mRNAs using the RNA-seq method for Zbtb1-deficient EL4 cells and performed a clustering analysis of differentially expressed lncRNAs and mRNAs. GO term histograms and KEGG scatter plots were drawn. For the experimental results, a joint analysis was performed, which predicted the regulatory relationships among lncRNAs, mRNAs, microRNAs and circRNAs. For the regulatory relationship between lncRNAs and target genes, the chromatin structure and the degree of openness were verified for the possible target gene locations regulated by lncRNA using experimental methods such as Hi-C and ATAC-seq. Ultimately, the possible differential regulation of the Brcal and Dennd5d genes by lncRNAs and the differential changes in transcription factor binding sites in the promoter region were identified. For neRNA-regulated target genes with significantly differentially expressed mRNAs, a combined screen was performed, and the final obtained candidate target genes were subjected to GO and KEGG term enrichment analyses. Our results illustrate that the Zbtb1 gene can not only function as a regulatory factor but also regulate EL4 cells from multiple perspectives based on ceRNA theory.


Machine learning-based classification of circadian rhythm characteristics for mild cognitive impairment in the elderly.
Using wrist-wearable sensors to ecological transient assessment may provide a more valid assessment of physical activity, sedentary time, sleep and circadian rhythm than self-reported questionnaires, but has not been used widely to study the association with mild cognitive impairment and their characteristics. 31 normal cognitive ability participants and 68 MCI participants were monitored with tri-axial accelerometer and nocturnal photo volumetric pulse wave signals for 14 days. Two machine learning algorithms: gradient boosting decision tree and eXtreme gradient boosting were constructed using data on daytime physical activity, sedentary time and nighttime physiological functions, including heart rate, heart rate variability, respiratory rate and oxygen saturation, combined with subjective scale features. The accuracy, precision, recall, F1 value, and AUC of the different models are compared, and the training and model effectiveness are validated by the subject-based leave-one-out method. The low physical activity state was higher in the MCI group than in the cognitively normal group between 8:00 and 11:00 (P < 0.05), the daily rhythm trend of the high physical activity state was generally lower in the MCI group than in the cognitively normal group (P < 0.05). The peak rhythms in the sedentary state appeared at 12:00-15:00 and 20:00. The peak rhythms of rMSSD, HRV high frequency output power, and HRV low frequency output power in the 6h HRV parameters at night in the MCI group disappeared at 3:00 a.m., and the amplitude of fluctuations decreased; the amplitude of fluctuations of LHratio nocturnal rhythm increased and the phase was disturbed; the oxygen saturation was between 90 and 95% and less than 90% were increased in all time periods (P < 0.05). The F1 value of the two machine learning algorithms for MCI classification of multi-feature data combined with subjective scales were XGBoost (78.02) and GBDT (84.04). By collecting PSQI Scale data combined with circadian rhythm characteristics monitored by wrist-wearable sensors, we are able to construct XGBoost and GBDT machine learning models with good discrimination, thus providing an early warning solution for identifying family and community members with high risk of MCI.


Small invasive breast carcinomas in Taiwanese women.
Female Taiwanese breast cancer patients are younger than their Western counterparts. This study examined the predictors of axillary lymph node metastases in Taiwanese women with T1 breast cancer. Data from 394 Taiwanese women with T1 invasive breast carcinoma were retrospectively reviewed. The data contained 6 T1a, 51 T1b, and 337 T1c breast tumors. The patients' ages ranged from 23 to 82 years (mean +/- SD, 48.2 +/- 11.4 years; median, 46.4 years). Axillary nodal metastases were present in 38.3% of the patients (16.7% in T1a, 35.3% in T1b, and 39.2% in T1c tumors). The patients with nodal metastases had significantly greater body weights and S-phase fractions than those without nodal metastases. Univariate analysis revealed that unfavorable pathology, lymphovascular invasion, S-phase fraction >7%, and nondiploid DNA ploidy were significantly associated with lymph node metastases. Lymphovascular invasion was the only significant variable as the independent predictor in the multiple logistic regression analysis. In the Cox proportional hazards regression analysis, axillary nodal status and lymphovascular invasion were significantly associated with survival. Taiwanese women with small breast cancer displayed a relatively higher incidence of axillary lymph node metastases than Western women. Axillary lymph node dissection or sentinel lymph node biopsy should be conducted on Taiwanese patients with small invasive breast carcinomas, particularly when risk factors exist.


Diagnostic strategies in the management of acute upper gastrointestinal bleeding: patient and physician preferences.
Routine diagnostic endoscopy is commonly obtained for low-risk patients with acute upper gastrointestinal bleeding despite evidence from controlled trials that it does not improve patient outcome. To determine whether endoscopy is being overutilized for these patients or whether considerations not addressed in the trials could justify its widespread use. Twenty-five patients recovering from a recent hemorrhage and 22 primary care physicians used the analytic hierarchy process to perform an individualized analysis regarding the diagnostic management of acute upper gastrointestinal bleeding. The results were used to determine whether routine endoscopy was consistent with each subject's interpretation of relevant data and judgments regarding the relative importance of five management goals. The authors then compared the proportion of subjects in each group who preferred endoscopy over two non-endoscopy strategies (upper gastrointestinal series and no routine diagnostic test) with 85%, the current rate of endoscopy at the authors' hospital. Endoscopy was preferred by 92% (97.5% CI: 70%-98%) of the patients and 55% (97.5% CI: 31%-77%) of the physicians. The patients ranked identifying the cause of bleeding the second most important management goal after avoiding a poor outcome from the acute bleeding episode. The current rate of diagnostic endoscopy is higher than would be expected based on physicians' preferences but quite consistent with patients' preferences. Patients regard knowledge of the bleeding site as important, even if this information will not affect management or prognosis. Attempts to assess the use of diagnostic endoscopy and other diagnostic tests should take both patient preferences and the pure value of diagnostic information into account.


Mixed neuroendocrine/Non-neuroendocrine neoplasm (MiNEN) of gastrointestinal lineage arising in an ovarian mature cystic teratoma.
•Mixed neuroendocrine/non-neuroendocrine neoplasm (MiNEN) of gastrointestinal lineage arising in an ovarian mature cystic teratoma is extremely rare.•It is important to differentiate the gastrointestinal-type adenocarcinoma arising along with neuroendocrine tumor from a primary mucinous adenocarcinoma of the ovary. SATB2 and CDX2 Immunohistochemical stains play important role in differentiate these two.•This case highlights the careful morphologic evaluation and extensive sampling is crucial to make this rare diagnosis.


Habitat dependent pollination success in a Cape orchid.
We examined the pollination success of Disa uniflora (Orchidaceae) in two habitats. Plants occurring in a rocky gorge were far more successful than plants occurring in an adjacent open valley. More than 55% of flowers in the gorge were pollinated and set fruit compared with less than 25% of flowers in the valley. These differences are explained by the preference of Meneris tulbaghia (Satyridae), the exclusive pollinator of the orchid, for rocky, sheltered habitats. Fruit set of hand-pollinated flowers did not differ significantly between the two habitats, indicating that resources did not account for the variation in fruiting success.


Regulatory crosstalk between Hox genes and miRNAs during angiogenesis.
Angiogenesis, or the growth of new blood vessels, is critical to both health and disease. Several genes are implicated in the regulation of angiogenesis, such as genes encoding growth factors, cytokines, and the extracellular matrix, as well as transcription factors. Among them, Hox genes exert master regulatory effects on several aspects of angiogenesis. The mechanism by which Hox genes are controlled is not well understood. However, recently microRNAs (miRNAs) have been introduced as candidates for Hox gene regulation. This review provides a comprehensive description of Hox genes and miRNAs involved in angiogenesis and presents possible regulatory interactions between them.


The effect of parasitization by Trichogramma australicum on Helicoverpa armigera host eggs and embryos.
Histological investigations of the pathology of Helicoverpa armigera (Hübner) eggs after attack by the egg parasitoid, Trichogramma australicum (Girault), indicate that the developing embryo is immediately killed by envenomation. Soon afterward the histological staining characteristics of parasitized host embryos change and the embryonic germ band dissociates into a mass of individual rounded cells. Hosts attacked by females sterilized by gamma-irradiation showed the same pathological effects as normally parasitized hosts, indicating that host degeneration is due to female venom rather than factors derived from the parasitoid embryo or larva. Cell death also occurred in older host embryos although tissue breakdown was delayed. These findings have allowed us to determine not just that the host dies but what happens to the cells and tissues, i.e., their physical appearance, the time course of their degeneration, and that the process is retarded in older hosts. These processes can possibly be emulated in artificial diets.


Early detection of COPD in general practice: patient or practice managed? A randomised controlled trial of two strategies in different socioeconomic environments.
The burden of chronic obstructive pulmonary disease (COPD) is high. Health benefits can be gained in primary care by early detection and preventive measures. To compare the effectiveness of two strategies for population-based early detection of COPD, taking into account different socioeconomic status (SES) settings. Practices were randomised on strategy and stratified on SES setting. The Respiratory Health Screening Questionnaire (RHSQ) was distributed to all participants. In the practice-managed condition, the practice was responsible for the whole procedure, while in the patient-managed condition, patients were responsible for calculating their RHSQ risk score and applying for a spirometry test. The main outcome measure was the rate of COPD diagnoses after screening. More new COPD patients were detected in the practice-managed condition (36%) than in the patient-managed condition (18%). In low SES practices, more high-risk patients were found (16%) than in moderate-to-high SES practices (9%). Recalculated for a standard Dutch practice (2,350 patients), the yield would be 8.9 new COPD diagnoses, which is a 20% increase of known cases. The practice-managed variant of this screening procedure shows a substantial yield of new COPD diagnoses for both low and moderate-to-high SES practices.


Evidence for the coexistence of glutamate decarboxylase and Met-enkephalin immunoreactivities in axon terminals of rat ventral pallidum.
Evidence for the coexistence of glutamate decarboxylase (GAD) and Met-enkephalin (Met-Enk) in axon terminals of ventral pallidum was demonstrated by colocalization of anti-GAD and anti-Met-Enk immunoreactivities in alternate adjacent 1 micron serial sections. Conventional electron microscopy of immunostained ventral pallidum confirmed that the immunoreactive structures were boutons which made predominantly symmetrical synapses on ventral pallidal cell bodies and dendrites.


A comparative analysis of rural and urban mortality in Georgia, 1979.
This paper examines the relationship between mortality and ruralness in the state of Georgia. In 1979, the rural Standardized Mortality Ratio (SMR) for deaths from all causes was significantly higher than expected when compared to statewide levels, while the urban SMR was significantly lower (p less than 0.01). Of the 13 leading causes of death, 9 had rural SMRs significantly higher than expected, while only homicide had a significantly greater urban SMR (p less than 0.01). Although much of the rural/urban difference in overall mortality is attributed to the fact that the rural population is older, figures adjusted for age and race still reveal that the rural death rate is significantly higher than the urban rate (p less than 0.01). Furthermore, there are several specific differences when analyzed by cause of death, age, and race that remain unexplained. Specific rural health problems include congenital anomalies, motor vehicle and other accidents, heart disease, and cerebrovascular disease. Specific urban health problems include homicides and cancer. In addition to metropolitan status, a second indicator of ruralness, county population size, was used to analyze the data and produced similar results. As county population size increases, the total mortality decreases.


Assembly, intracellular localization, and nucleotide binding properties of the human peptide transporters TAP1 and TAP2 expressed by recombinant vaccinia viruses.
The transporter associated with antigen processing (TAP) transports short peptides from the cytosol to the endoplasmic reticulum, where peptides assemble with class I molecules of the major histocompatibility complex. TAP is comprised of two subunits, termed TAP1 and TAP2. We produced recombinant vaccinia viruses that direct synthesis of the TAP subunits, either individually or together. Virus-encoded TAP is rapidly and efficiently assembled (t1/2 of 5 min or less) by cells and does not spontaneously assemble in detergent extracts. By confocal immunofluorescence microscopy, TAP1 when expressed alone or with TAP2 is largely, if not exclusively, localized to the endoplasmic reticulum. Metabolic labeling with [2-3H]mannose demonstrates that TAP1 (but not TAP2) possesses Asn-linked oligosaccharides, but the lack of binding of [35S]methionine-labeled TAP to concanavalin A-agarose suggests that the glycosylated form represents a minor population of TAP1. The two subunits of the assembled complex present in detergent extracts photolabeled equally with 8-azido-[alpha-32P]ATP. Photolabeling of the two subunits was inhibited in parallel by various di- and trinucleotides, suggesting that their nucleotide binding sites function in a highly similar manner. Incubation of detergent extracts at 37 degrees C results in the rapid loss of TAP1 immunoreactivity, indicating either an unusual sensitivity to proteases or an irreversible conformation alteration.


Laboratory-based study of novel antimicrobial cold spray coatings to combat surface microbial contamination.
To investigate the touch-contact antimicrobial efficacy of novel cold spray surface coatings composed of copper and silver metals, regard to their rate of microbial elimination. Antimicrobial time-kill assay. Laboratory-based study. An adapted time-kill assay was conducted to characterize the antimicrobial efficacy of the developed coatings. A simulated touch-contact pathogenic exposure to Gram-positive Staphylococcus aureus (ATCC 25923), Gram-negative Pseudomonas aeruginosa (ATCC 27853), and the yeast Candida albicans (ATCC 10231), as well as corresponding resistant strains of gentamicin-methicillin-resistant S. aureus (ATCC 33592), azlocillin-carbenicillin-resistant P. aeruginosa (DSM 46316), and a fluconazole-resistant C. albicans strain was undertaken. Linear regression modeling was used to deduce microbial reduction rates. A >7 log reduction in microbial colony forming units was achieved within minutes on surfaces with cold spray coatings compared to a single log bacterial reduction on copper metal sheets within a 3 hour contact period. Copper-coated 3-dimensional (3D) printed acrylonitrile butadiene styrene (ABS) achieved complete microbial elimination against all tested pathogens within a 15 minute exposure period. Similarly, a copper-on-copper coating achieved microbial elimination within 10 minutes and within 5 minutes with the addition of silver powder as a 5 wt% coating constituent. In response to the global need for alternative solutions for infection control and prevention, these effective antimicrobial surface coatings were proposed. A longitudinal study is the next step toward technology integration.


A microsatellite polymorphism in intron 2 of human Toll-like receptor 2 gene: functional implications and racial differences.
The human Toll-like receptor 2 (TLR2) mediates responses of both innate and adaptive immunity to Gram-positive bacteria, including mycobacteria. We sought functional polymorphisms in the 5'-untranslated region (UTR) of TLR2. We found a highly polymorphic (GT)n dinucleotide repeat 100 bp upstream of the TLR2 translational start site in intron 2. The numbers of GT repeats varied from 12 to 28. There were significant differences in allele distribution between African Americans and Caucasians (P=0.008) and between African Americans and Koreans (P=0.0003). The promoter activities of recombinant promoter-intron2/reporter constructs including the shortest [GT)n=12] or longest [(GT)n=28] alleles were significantly more stimulated when exposed to 200 IU ml(-1) of interferon-gamma than when exposed to 100 IU ml(-1) of GM-CSF (P<==0.03). Since TLR2 plays a critical role in the human innate immune response, this functional microsatellite polymorphism may be important in the pathogenesis of infectious and inflammatory diseases.


The Influence of Hyperoxygenation on Fetal Brain Vascularity Measured Using 3D Power Doppler Ultrasound and the Index "Fractional Moving Blood Volume".
Maternal hyperoxygenation effects on fetal cerebral hemodynamics are largely unknown. This study aimed to determine efficacy and reliability of a validated power Doppler ultrasound (US) index, fractional moving blood volume (FMBV), at measuring fetal cerebral vasculature changes during maternal hyperoxia. The fetal cerebral effects of 10 min of hyperoxygenation at 2 flow rates (52%/60% FiO2) were evaluated in women in their third trimester of pregnancy. 2D-US and 3D-US in a transverse plane were performed before, during, and following maternal hyperoxygenation with FMBV estimation performed offline. Forty-five cases provided data for analysis. Mean intraobserver ICCs were 0.89 (3D-FMBV) and 0.84 (2D-FMBV). A significant difference in vascularity before and during and before and after 60% hyperoxia was observed (p < 0.05), whereas no significant differences were found at 52% hyperoxia (p > 0.05). Significant differences in vascularity were found between 2D-FMBV and 3D-FMBV (p < 0.01). Measurement of fetal cerebral vascularity by 3D-FMBV and 2D-FMBV was highly reproducible. The differing cerebral vascular changes seen with 60% but not 52% FiO2 suggest a possible "threshold effect" that may have influenced prior studies. Further studies are needed to assess cerebral effects of maternal hyperoxygenation on compromised fetuses.


Plasmid as a measure of microbial degradation capacity for 2,4-dichlorophenoxyacetic acid.
The purpose of this research was to pursuit the quantification of microbial degradation capacity for 2,4-dichlorophenoxyacetic acid (2,4-D) by detecting and quantifying a prominent 2,4-D degradation encoding plasmid. Batch reactor acclimation, de-acclimation, and re-acclimation tests were conducted during which periods the courses of 2,4-D dissipation and plasmid evolution were quantitatively measured. Pure cultures of bacterial strains were detected to give rise to a plasmid approximately the size of 90 kb after acclimation. The 90 kb plasmid content of Arthrobacter sp. increased when degradation occurred after acclimation, with a rate that corresponded closely to the degradation rate. During de-acclimation, plasmid content declined exponentially at a half-life of approximately 3.5 days. Re-acclimation saw a renewed induction of plasmid, but substrate consumption limited the rise of plasmid to a level much lower than after the first acclimation. This research recommends a method for measuring the microbial degradation capability for a xenobiotic.


Sequential triage of transmembrane segments by Sec61alpha during biogenesis of a native multispanning membrane protein.
During polytopic protein biogenesis, the Sec61 translocon must rapidly orient and integrate multiple transmembrane segments (TMs) into the endoplasmic reticulum membrane. To understand this process, we examined interactions between Sec61alpha and all six TMs of the aquaporin-4 (AQP4) water channel at defined stages of synthesis using incorporated photo-cross-linking probes. Each TM interacted with and moved through the translocon in a highly ordered and sequential fashion. Strong asymmetric Sec61alpha cross-linking was observed for only one helix at a time, suggesting the presence of a single primary binding site. However, up to four TMs simultaneously contacted Sec61alpha from different molecular environments. Thus, AQP4 integration by Sec61alpha involves sequential triage of TMs from their initial portal of entry into multiple secondary sites within the translocon. This mechanism provides a means to facilitate early folding events before release into the lipid bilayer.


Acalculous cholecystitis in severely burned patients: incidence and predisposing factors.
To investigate the incidence and predisposing factors of acalculous cholecystitis (AAC) in severely burned patients. Although some studies report on AAC in critically ill patients, very little is known about AAC after severe burns. We conducted a retrospective cohort study involving patients with burns admitted to the burn intensive care unit (BICU) of a university hospital. The patient cohort was divided into two groups (AAC group: burned patients with histological proven acalculous cholecystitis, n=15; population of all other burned patients admitted to the BICU, n=1225). Univariate and multivariate analyses were used to identify predisposing factors for the development of AAC. Fifteen patients with acalculous cholecystitis were identified in the study period. This represents 1.2% of all significant burns admitted. Comparing the AAC group with the Control population the following patients' characteristics, therapeutic measures and outcome parameters were significantly different in the univariate analysis: mean age (54.0 years vs. 42.0 years), BMI (28.9 kg/m(2) vs. 25.6 kg/m(2)), abbreviated burn severity index (8.3 vs. 6.4), total body surface area burn deep partial thickness (12.0% vs. 6.2%) and full thickness (10.2% vs. 6.8%), concomitant inhalation injury (80.0% vs. 28.9%), sepsis (46.7% vs. 14.9%), catecholamine (100% vs. 30.4%) and antibiotic requirement (100% vs. 58.2%), non-biliary tract operations (4.9 vs. 1.5), BICU length of stay (63.4 days vs. 21.0 days), ventilator days (50.3 vs. 11.9), packed red blood cells (PRBCs) administration (70.0 units vs.13.0 units) and mortality (53.3% vs. 19.7%). In the multivariate analysis however, only age, the number of administered units of PRBCs and the duration of mechanical ventilation turned out to be independent predictors for the occurrence of AAC. AAC is a rare complication of severely burned patients and may reflect the severity of the patient's general conditions. Predisposing factors for AAC are advanced age, the need of blood transfusions and prolonged mechanical ventilation. In the presence of these predisposing factors, early monitoring may help to detect AAC earlier and to initiate appropriate intervention.


Protective effect of breast feeding against infection.
To assess the relations between breast feeding and infant illness in the first two years of life with particular reference to gastrointestinal disease. Prospective observational study of mothers and babies followed up for 24 months after birth. Community setting in Dundee. 750 pairs of mothers and infants, 76 of whom were excluded because the babies were preterm (less than 38 weeks), low birth weight (less than 2500 g), or treated in special care for more than 48 hours. Of the remaining cohort of 674, 618 were followed up for two years. Detailed observations of infant feeding and illness were made at two weeks, and one, two, three, four, five, six, nine, 12, 15, 18, 21, and 24 months by health visitors. The prevalence of gastrointestinal disease in infants during follow up. After confounding variables were corrected for babies who were breast fed for 13 weeks or more (227) had significantly less gastrointestinal illness than those who were bottle fed from birth (267) at ages 0-13 weeks (p less than 0.01; 95% confidence interval for reduction in incidence 6.6% to 16.8%), 14-26 weeks (p less than 0.01), 27-39 weeks (p less than 0.05), and 40-52 weeks (p less than 0.05). This reduction in illness was found whether or not supplements were introduced before 13 weeks, was maintained beyond the period of breast feeding itself, and was accompanied by a reduction in the rate of hospital admission. By contrast, babies who were breast fed for less than 13 weeks (180) had rates of gastrointestinal illness similar to those observed in bottle fed babies. Smaller reductions in the rates of respiratory illness were observed at ages 0-13 and 40-52 weeks (p less than 0.05) in babies who were breast fed for more than 13 weeks. There was no consistent protective effect of breast feeding against ear, eye, mouth, or skin infections, infantile colic, eczema, or nappy rash. Breast feeding during the first 13 weeks of life confers protection against gastrointestinal illness that persists beyond the period of breast feeding itself.


Improved laccase production from Pleurotus floridanus using deoiled microalgal biomass: statistical and hybrid swarm-based neural networks modeling approach.
Fungal laccases are versatile biocatalyst and occupy a prominent place in various industrial applications due to its broad substrate specificity. The simplest method to enhance the laccase production is by usage of cheap substrates in the fermentation processes incorporating modeling approaches for optimization. Integrated biorefinery concept is receiving wide popularity by making use of various products from microalgal biomass. The research aimed to identify the potential of deoiled microalgal biomass (DMB), a waste product from algal biorefinery as a nutrient supplement to enhance laccase production in Pleurotus floridanus by submerged fermentation. The maximum production was obtained in the presence of DMB as an additional nutrient supplement and copper sulfate as an inducer. The predictive capabilities of the two methodologies Response Surface Methodology (RSM) and hybrid Particle swarm optimization (PSO)-based Artificial Neural Network (ANN) were compared and validated. The results showed that ANN coupled with PSO predicted with more accuracy with an R 2 value of 0.99 than the RSM model with an R 2 value of 0.97. The optimized condition as predicted by superior model hybrid PSO-based ANN was glucose (3.51%), DMB (0.545%), pH (4.9), temperature (24.68 ℃) and CuSO4 (1.35 mM). The experimental laccase activity was 80.45 ± 0.132 U/mL which was 1.3 fold higher than unoptimized condition. This study promotes the usage of DMB as a novel supplement for the improved production of Pleurotus floridanus laccase. The online version contains supplementary material available at 10.1007/s13205-022-03404-y.


The risk to the United Kingdom population of zinc cadmium sulfide dispersion by the Ministry of Defence during the "cold war".
To estimate exposures to cadmium (Cd) received by the United Kingdom population as a result of the dispersion of zinc Cd sulfide (ZnCdS) by the Ministry of Defence between 1953 and 1964, as a simulator of biological warfare agents. A retrospective risk assessment study was carried out on the United Kingdom population during the period 1953-64. This determined land and air dispersion of ZnCdS over most of the United Kingdom, inhalation exposure of the United Kingdom population, soil contamination, and risks to personnel operating equipment that dispersed ZnCdS. About 4600 kg ZnCdS were dispersed from aircraft and ships, at times when the prevailing winds would allow large areas of the country to be covered. Cadmium released from 44 long range trials for which data are available, and extrapolated to a total of 76 trials to allow for trials with incomplete information, is about 1.2% of the estimated total release of Cd into the atmosphere over the same period. "Worst case" estimates are 10 microg Cd inhaled over 8 years, equivalent to Cd inhaled in an urban environment in 12100 days, or from smoking 100 cigarettes. A further 250 kg ZnCdS was dispersed from the land based sites, but significant soil contamination occurred only in limited areas, which were and have remained uninhabited. Of the four personnel involved in the dispersion procedures (who were probably exposed to much higher concentrations of Cd than people on the ground), none are suspected of having related illnesses. Exposure to Cd from dissemination of ZnCdS during the "cold war" should not have resulted in adverse health effects in the United Kingdom population.


Emergence of a clone of invasive fucK-negative serotype e Haemophilus influenzae in British Columbia.
Introduction of the Haemophilus influenzae serotype b (Hib) conjugate vaccine has changed the epidemiology of invasive H. influenzae disease, with most infections now caused by non-typeable (non-encapsulated) and non-Hib encapsulated strains. We describe nine invasive serotype e H. influenzae (Hie) from British Columbia that were determined to have complete deletion of their fucose operon genes. These nine isolates were recovered from blood cultures of three female and six male patients during 2011-2018, with eight recovered in the past 4 years. All nine isolates were biotype IV, with eight showing identical pulsed field gel electrophoresis (PFGE) profiles, whereas the ninth showed 95% similarity. PFGE analysis also showed these fucose operon-negative Hie to be most (94%) similar to the multi-locus sequence type (ST)-18, the most common ST among Hie in British Columbia. These nine fucose operon-negative Hie represented 27.3% of the 33 invasive Hie isolated in British Columbia from 2010 to 2018. Deletion of the fucose operon did not appear to impact the transmission ability of these strains or their ability to cause invasive disease.


Experimental studies on direct and indirect interactions in a three trophic-level stream system.
We used a complete block design to experimentally study direct and indirect interactions in a three trophic-level freshwater system consisting of a top predator, the green sunfish, Lepomis cyanellus, an intermediate predator, small-mouthed salamander larvae, Ambystoma barbouri, and prey, hatchling isopods, Lirceus fontinalis. This system occurs naturally in small stream pools in central Kentucky; experiments were done in laboratory pools. Salamander larvae ate isopods and thus had a direct, negative effect on isopod survival. Accordingly, isopods responded to the presence of salamander larvae by increasing their tendency to bury themselves in the sand substrate. Fish ate salamanders and thus had a direct, negative effect on salamander survival. Salamanders responded to fish presence by increasing their time spent under plexiglass plates that simulate refuge rocks. The overall effect of fish on isopods depended on the presence of salamanders. In the absence of salamanders, fish predation on isopods had a direct, negative effect on isopod survival; isopods thus responded to the presence of fish by burying themselves in the sand. With salamanders present, fish had a positive overall effect on isopod survival; i.e., direct, negative effects of fish on isopods were outweighed by indirect, positive effects. Indirect positive effects of fish on isopods came through a reduction in salamander predation rates on isopods in the presence of fish. The mechanism involved both a decrease in the number of salamanders (a trophic-linkage indirect effect; cf. Miller and Kerfoot 1987) and a reduction in the feeding rate of individual salamanders on isopods (a behavioral indirect effect). The decrease in individual salamander feeding rates on isopods was due to reductions in both salamander activity and in spatial overlap between salamanders and isopods in the presence of fish. The latter effect reflected the fact that salamanders and isopods used different refuges from fish; salamanders went under refuge plates, whereas isopods primarily buried themselves in sand. Estimates of the relative importance of various direct and indirect effects of sunfish on isopods suggested that positive, behavioral indirect effects were of roughly the same magnitude as direct, negative effects, both of which were more important than were trophic-linkage indirect effects. Contrary to expectations, the presence of isopods did not affect the refuge use or survival of salamanders in the presence of fish.


Home Testing May Not Improve Postvasectomy Semen Analysis Compliance.
Vasectomy is the most effective form of permanent male contraception. Although vasectomy techniques and outcomes have steadily improved, postvasectomy semen analysis compliance remains a significant challenge. The aim of this study was to assess if home testing improved postvasectomy semen analysis compliance. Data were collected prospectively but retrospectively reviewed between 2007 and 2019 from a single surgeon's high volume practice. Subjects were divided into 2 groups based on postvasectomy semen analysis method (home vs office) and further subdivided by compliance status. Patients were considered compliant if they provided at least 1 semen sample postvasectomy. Statistical analysis was completed to determine factors predictive of compliance. A total of 364 patients were included. Median age for the home group vs the office group was similar (42 years [IQR 39-46] vs 41 years [IQR 38-46]). Median number of children for both groups was 2 (IQR 2-3). In all, 109 men (30.0%) opted for at-home testing. No significant difference in compliance was found (59.6% of home test vs 58.8% of laboratory patients, p=0.89). No statistically significant difference in patient demographics (age, partner age, number of children, smoking and alcohol) was observed, and there were no demographic factors predicting compliance with regression modeling. At-home semen analysis kits did not significantly improve compliance. Clinicians should be aware that this may be a reasonable alternative for those who are unable to obtain a postvasectomy semen analysis in-office. Contact of the female partner instead may improve postvasectomy semen analysis compliance as the female partner has a stake in ensuring postvasectomy semen analysis azoospermia.


Cloning of human heparan sulfate proteoglycan core protein, assignment of the gene (HSPG2) to 1p36.1----p35 and identification of a BamHI restriction fragment length polymorphism.
We have isolated a cDNA coding for the core protein of the large basement membrane heparan sulfate proteoglycan (HSPG) from a human fibrosarcoma cell (HT1080) library. The library was screened with a mouse cDNA probe and one clone obtained, with a 1.5-kb insert, was isolated and sequenced. The sequence contained an open reading frame coding for 507 amino acid residues with a 84% identity to the corresponding mouse sequence. This amino acid sequence contained several cysteine-rich internal repeats similar to those found in component chains of laminin. The HSPG cDNA clone was used to assign the gene (HSPG2) to the p36.1----p35 region of chromosome 1 using both somatic cell hybrid and in situ hybridization. In the study of the polymorphisms of the locus, a BamHI restriction fragment length polymorphism was identified in the gene. This polymorphism displayed bands of 23 and 12 kb with allele frequencies of 76 and 24%, respectively.