Poor peer relations predict parent- and self-reported behavioral and emotional problems of adolescents with gender dysphoria: a cross-national, cross-clinic comparative analysis.
This study is the third in a series to examine behavioral and emotional problems in children and adolescents with gender dysphoria in a comparative analysis between two clinics in Toronto, Ontario, Canada and Amsterdam, the Netherlands. In the present study, we report Child Behavior Checklist (CBCL) and Youth Self-Report (YSR) data on adolescents assessed in the Toronto clinic (n = 177) and the Amsterdam clinic (n = 139). On the CBCL and the YSR, we found that the percentage of adolescents with clinical range behavioral and emotional problems was higher when compared to the non-referred standardization samples but similar to the referred adolescents. On both the CBCL and the YSR, the Toronto adolescents had a significantly higher Total Problem score than the Amsterdam adolescents. Like our earlier studies of CBCL data of children and Teacher's Report Form data of children and adolescents, a measure of poor peer relations was the strongest predictor of CBCL and YSR behavioral and emotional problems in gender dysphoric adolescents.


Differences in handedness and scores of aggressiveness and interpersonal relations of soccer players.
Handedness and differences in interpersonal relations and aggressiveness were studied in 33 right-handed (M age=22.9 yr., SD=4.9) and 18 left-handed (M age=22.5 yr., SD=2.4) male soccer players who played actively in professional soccer leagues of Turkey. Hand preference on the Edinburgh Handedness Inventory and scores for destructiveness, assertiveness, and passive aggressiveness on a Turkish Aggressiveness Inventory, plus scores for sociability, benevolence, tenderheartedness, tolerance, and insistence on the Turkish Interpersonal Relations Inventory were examined. Mean destructive aggressiveness was higher for the left- than the right-handed athletes. Means on tolerance and insistence were higher for the right- than the left-handed athletes. Higher aggressiveness and less tolerance and insistence in the left-handers may be associated with their higher sports performance.


The impact of vaccination on the burden of invasive pneumococcal disease from a nationwide surveillance program in Lebanon: an unexpected increase in mortality driven by non-vaccine serotypes.
The impact of pneumococcal conjugate vaccines (PCVs) on the burden of invasive pneumococcal disease (IPD) and serotype distribution was examined across age groups from data collected by the Lebanese Inter-Hospital Pneumococcal Surveillance Program. Between 2005 and 2020, 593 invasive Streptococcus pneumoniae isolates were collected from 79 hospitals throughout Lebanon. Serotypes and antimicrobial resistance (AMR) profiles were identified, and trends compared over 3 eras: PCV7, post-PCV7/ pre-PCV13, and PCV13 eras. The prevalence of PCV7 serotypes decreased significantly from 43.6% in the PCV7 era to 17.8% during the PCV13 era (p<0.001). PCV13-only serotypes remained stable in the PCV13 compared to the post-PCV7 eras, especially serotypes 1 and 3, whereas non-vaccine types (NVT) increased throughout the study period, especially 24 and 16F. The mortality rate increased substantially from 12.5% (PCV7 era) to 24.8% (PCV13 era). A significant decrease in AMR was observed across the three study eras. PCVs substantially impacted IPD and AMR in vaccinated and unvaccinated populations despite an increase in mortality driven by NVT. Broadening the recommendation of vaccination to include older age-groups, using higher valency vaccines, and implementing stringent antimicrobial stewardship are likely to further impact the burden of IPD.


Genetic studies, clinical heterogeneity, and disease outcome studies in rheumatoid arthritis.
HLA haplotypes influence various clinical RA features considered to reflect severity in case-control and cohort studies. Of particular note is the fact that HLA generally influences the development of erosive and sometimes seropositive and nodular disease; in prospective studies, it noticeably affects joint surgical intervention. These are valuable clues indicating that HLA influences RA severity and chronicity. Nevertheless, HLA influences are generally weak enough so as to require large study subject numbers for detection. As a result, HLA genotyping has restricted usefulness for prediction of clinical severity in individual patients.


Testing the therapeutic effects of transcranial direct current stimulation (tDCS) in semantic dementia: a double blind, sham controlled, randomized clinical trial.
Semantic dementia is a neurodegenerative disease that primarily affects the left anterior temporal lobe, resulting in a gradual loss of conceptual knowledge. There is currently no validated treatment. Transcranial stimulation has provided evidence for long-lasting language effects presumably linked to stimulation-induced neuroplasticity in post-stroke aphasia. However, studies evaluating its effects in neurodegenerative diseases such as semantic dementia are still rare and evidence from double-blind, prospective, therapeutic trials is required. The primary objective of the present clinical trial (STIM-SD) is to evaluate the therapeutic efficacy of a multiday transcranial direct current stimulation (tDCS) regime on language impairment in patients with semantic dementia. The study also explores the time course of potential tDCS-driven improvements and uses imaging biomarkers that could reflect stimulation-induced neuroplasticity. This is a double-blind, sham-controlled, randomized study using transcranial Direct Current Stimulation (tDCS) applied daily for 10 days, and language/semantic and imaging assessments at four time points: baseline, 3 days, 2 weeks and 4 months after 10 stimulation sessions. Language/semantic assessments will be carried out at these same 4 time points. Fluorodeoxyglucose positron emission tomography (FDG-PET), resting-state functional magnetic resonance imaging (rs-fMRI), T1-weighted images and white matter diffusion tensor imaging (DTI) will be applied at baseline and at the 2-week time point. According to the principle of inter-hemispheric inhibition between left (language-related) and right homotopic regions we will use two stimulation modalities - left-anodal and right-cathodal tDCS over the anterior temporal lobes. Accordingly, the patient population (n = 60) will be subdivided into three subgroups: left-anodal tDCS (n = 20), right-cathodal tDCS (n = 20) and sham tDCS (n = 20). The stimulation will be sustained for 20 min at an intensity of 1.59 mA. It will be delivered through 25cm2-round stimulation electrodes (current density of 0.06 mA/cm2) placed over the left and right anterior temporal lobes for anodal and cathodal stimulation, respectively. A group of healthy participants (n = 20) matched by age, gender and education will also be recruited and tested to provide normative values for the language/semantic tasks and imaging measures. The aim of this study is to assess the efficacy of tDCS for language/semantic disorders in semantic dementia. A potential treatment would be easily applicable, inexpensive, and renewable when therapeutic effects disappear due to disease progression. ClinicalTrials.gov NCT03481933. Registered on March 2018.


Community acceptance of residential programs for developmentally disabled persons.
Deinstitutionalization and the ensuing establishment of residence programs for developmentally disabled persons has stimulated both community support and opposition. The present study considers changes in the levels of community acceptance after residence programs are established, sources of program support and opposition, and strategies used to overcome community opposition. The data are based upon responses to a survey of all community residence programs in New York (n = 459). The findings indicate marked and consistent shifts toward the acceptance of established residence programs.


Membrane vesicles traffic signals and facilitate group activities in a prokaryote.
Many bacteria use extracellular signals to communicate and coordinate social activities, a process referred to as quorum sensing. Many quorum signals have significant hydrophobic character, and how these signals are trafficked between bacteria within a population is not understood. Here we show that the opportunistic human pathogen Pseudomonas aeruginosa packages the signalling molecule 2-heptyl-3-hydroxy-4-quinolone (pseudomonas quinolone signal; PQS) into membrane vesicles that serve to traffic this molecule within a population. Removal of these vesicles from the bacterial population halts cell-cell communication and inhibits PQS-controlled group behaviour. We also show that PQS actively mediates its own packaging and the packaging of other antimicrobial quinolines produced by P. aeruginosa into vesicles. These findings illustrate that a prokaryote possesses a signal trafficking system with features common to those used by higher organisms and outlines a novel mechanism for delivery of a signal critical for coordinating group behaviour in P. aeruginosa.


Juvenile and adenomatous gastrointestinal polyposis.
This is the fourth report of a case showing an association between juvenile and adenomatous polyposis. Starting at age 14, this patient underwent multiple polypectomies and gastrointestinal resections over a 15-year period. Although initial biopsies were diagnosed as juvenile polyps, later biopsies showed both adenomatous polyps and large polypoid masses with a mixture of juvenile and adenomatous features. Several typical small hyperplastic polyps were also found in the stomach. This case contrasts with the previous three cases in that the gastrointestinal tract is more widely involved and in that there is an unusual marked hyperplasia of argentaffin- and argyrophil-positive cells. The case reported here strengthens the relation between adenomatous polyposis and juvenile polyposis.


A randomized phase II trial of bevacizumab vs. bevacizumab and erlotinib as first-line consolidation after carboplatin, paclitaxel, and bevacizumab in newly diagnosed patients with mullerian tumors.
The combination of paclitaxel to platinum remains the backbone of therapy in patients with advanced Mullerian tumors. In patients with newly diagnosed Mullerian tumors, we investigated the progression-free survival benefit of bevacizumab and bevacizumab and erlotinib as consolidation therapy post-induction therapy. Sixty patients were enrolled in a phase II trial of carboplatin, paclitaxel, and bevacizumab (induction therapy). After the completion induction therapy, patients were stratified by response (≥ SD) and then randomized (1:1) to either bevacizumab (A) or bevacizumab and erlotinib (AE.) The primary endpoint was PFS. Secondary endpoints included the response rate of induction and consolidation therapy and toxicity profile of each consolidative arm. Each consolidative arm was compared to the historical control GOG 111. Forty-eight patients advanced to the consolidative phase of the trial. Twelve patients were removed in the induction phase, the majority for toxicity. The most common toxicity (grade ≥ 3) was diarrhea (20%: arm AE; 0%: arm A). One patient in the AE arm had a fatal cardiac arrest deemed unrelated to the study treatment. No gastrointestinal perforations were reported. The median PFS in the AE and A arm was 18.9 months (p < 0.0001) and 13.3 months (p: ns), respectively. The overall rate of grade 3/4 toxicities in the AE arm was 72% and in the A arm 30%. Six patients remain free of disease 10 years after enrollment. Combinatorial consolidation therapy with AE was associated with an improved progression-free survival in patients with Mullerian tumors.


Topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel.
Actinic keratoses (AKs) are premalignant skin lesions, which, if left untreated, can develop into squamous cell carcinoma. Current treatments for AKs are destructive and are often associated with significant adverse events. The development of an effective and well-tolerated topical treatment for AK is desirable. To evaluate the efficacy and safety of 3.0% diclofenac in 2.5% hyaluronan gel as a treatment for AK. This was a multicentre, double-blind, placebo-controlled study in which 195 patients with at least five AKs in up to three designated treatment blocks were randomized to four treatment groups. Patients randomized into the active treatment groups A30 (n = 49) and A60 (n = 48) received topical treatment with 3.0% diclofenac in 2.5% hyaluronan gel 0.5 g twice daily for 30 or 60 days, respectively. Patients in the placebo (vehicle gel) groups V30 (n = 49) and V60 (n = 49) received topical treatment with 2.5% hyaluronan gel 0.5 g twice daily for 30 or 60 days, respectively. Treatment efficacy was assessed by target and cumulative lesion number scores (TLNS and CLNS, respectively) and lesion total thickness score (TTS). Investigator and patient global improvement indices (IGII and PGII) were also used to rate overall improvement. Compared with placebo, significantly more patients given active treatment for 60 days had TLNS = 0 (33% vs. 10%, P < 0.05; an improvement of 64% compared with 34% with placebo), CLNS = 0 (31% vs. 8%, P < 0.05; an improvement of 54% compared with 23% with placebo) and TTS = 0 (25% vs. 6%, P < 0.05; an improvement of 59% compared with 31% with placebo). The IGII and PGII scores were also significantly better when active treatment was compared with placebo (P < 0.05). Both treatments were generally well tolerated and the incidence of the most common adverse events was similar between groups. Treatment with 3.0% diclofenac in 2.5% hyaluronan gel was effective when used for 60 days and was well tolerated in patients with AK.


Multiple myeloma: 2022 update on diagnosis, risk stratification, and management.
Multiple myeloma accounts for approximately 10% of hematologic malignancies. The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy-proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) attributable to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥ 100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging. The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high-risk multiple myeloma. The presence of any two high risk factors is considered double-hit myeloma, and three or more high risk factors is triple-hit myeloma. In patients who are candidates for autologous stem cell transplantation, induction therapy consists of bortezomib, lenalidomide, dexamethasone (VRd) given for approximately 3-4 cycles followed by autologous stem cell transplantation (ASCT). In high-risk patients, daratumumab, bortezomib, lenalidomide, dexamethasone (Dara-VRd) is an alternative to VRd. Selected standard-risk patients can collect stem cells, get additional cycles of induction therapy, and delay transplant until first relapse. Patients who are not candidates for transplant are treated with VRd for approximately 8-12 cycles followed by maintenance or alternatively with daratumumab, lenalidomide, dexamethasone (DRd) until progression. Standard-risk patients need lenalidomide maintenance, while bortezomib plus lenalidomide maintenance is needed for high-risk myeloma. A triplet regimen is usually needed at relapse, with the choice of regimen varying with each successive relapse.


Reexamination of the effect of urinary kallikrein on renin release: evidence that kallikrein does not release renin but protects renin from destruction.
Previously, we showed that superfusion of rat kidney slices by rat urinary kallikrein stimulated renin release. The resin measurements were performed on superfusion samples which we stored frozen at -20 C for 24 h. In this study we investigated the effect of freezing on the renin concentration of superfusion samples in the control period. The renin concentration measured immediately without freezing was 9.8 +/- 2.4 ng angiotensin I/10 ml . 3 h/mg tissue, while the concentration in the samples frozen for 24 h was 2.9 +/- 1.0 ng angiotensin I/10 ml . 3 h/mg. The renin concentration of the superfusion samples during the kallikrein perfusion period was the same as that of the nonfrozen control samples. It appeared, therefore, that kallikrein acted as if it stimulated renin release from kidney slices, when the renin was measured in frozen samples. To clarify this phenomenon, we added kallikrein, inactivated kallikrein, and albumin to superfusion samples of the control period and froze the samples for 24 h. After freezing, the renin concentration of the control samples decreased to about 20% of that of nonfrozen samples, except in those samples to which the various proteins were added. In these samples, the loss of renin activity was prevented. The addition of Trasylol, a specific inhibitor of kallikrein, blocked the protective effect of both kallikrein and albumin. These data suggest that the renin released into the superfusion media of kidney slices is destroyed by freezing and that kallikrein or BSA prevents this destruction. These data negate previous data indicating that kallikrein stimulates renin release.


Specialists' management decisions and attitudes towards mucositis and peri-implantitis.
Pathology of the peri-implant tissues, namely peri-implant mucositis and peri-implantitis are conditions that are often encountered and can threaten the long term survival of the implants. This study aimed to compare the attitudes of registered specialists in periodontology in Australia and the UK towards aetiology, prevalence, diagnosis and management of mucositis and peri-implantitis. A validated questionnaire was used and the sample consisted of UK and Australian specialists. There were differences in the demographics of specialists in the two countries, with the Australian specialists being significantly younger. Most specialists in both countries identified the prevalence of peri-implant pathology between 0-25%. Although there was agreement as to the role of plaque in the aetiopathogenesis of the diseases, UK specialists were more likely to include adverse loading and smoking as etiological factors. There were significant differences in the management of the disease between the groups, including the use of mouth rinses, local and systemic antibiotics. Australians were more likely to use systemic antibiotics than in the UK. The results suggested that differences in professional demographics, educational resources and market factors, and the absence of consensus treatment standards can significantly affect the treatment modalities patients finally receive.


The placental syncytium and the pathophysiology of preeclampsia and intrauterine growth restriction: a novel assay to assess syncytial protein expression.
Preeclampsia is associated with an increased release of factors from the placental syncytium into maternal blood, including the antiangiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin, the antifibrinolytic factor plasminogen activator inhibitor-1, prostanoids, lipoperoxides, cytokines, and microparticles. These factors are suggested to promote maternal endothelium dysfunction and are associated with placental damage in pregnancies also complicated with intrauterine growth restriction (IUGR). In this report, we briefly describe the interaction of syncytial factors with hypoxia, reactive oxygen species, and apoptosis in the pathophysiology of preeclampsia and IUGR. Given the critical role of the syncytium in these complications of pregnancy, we also present a novel methodology in which laser capture microdissection followed by Western blotting is used to assess levels of syncytial Fas ligand, a key protein in the apoptotic cascade.


Electrophysiological estimation of the function of different retinal zones in normal eyes and in retinal degenerations.
By means of electroretinographical responses from different areas of the retina (zonular ERGs) both healthy people and patients with central and peripheral retinal degenerations were examined. Responses were registered from three retinal areas (zones): central (red, green, and blue stimuli, 10 degrees in diameter, during adaptation of 20 lux); paramacular (a dim, blue, ringlike stimulus, 15 degrees inner and 50 degrees outer diameter, presented at the beginning of dark adaptation) and peripheral (very dim, blue ring stimulus of a 50 degree inner and 110 degrees outer diameter, after 3 min of dark adaptation). The data obtained by this method of stimulation give information about the function of stimulated retinal areas and provide new criteria for the function of the spectrally different photoreceptors responsible for intact color vision. Examples are presented that reveal the value of this method for the detection of congenital color vision defects and for the classification of different types of retinal degeneration. This method is shown to be highly effective and has many advantages over the common routine Ganzfeld ERG technique, especially in cases of unusual retinal degenerations.


Top-Down Mass Spectrometry Data Analysis Using TopPIC Suite.
With the advances of mass spectrometry (MS) techniques, top-down MS-based proteomics has gained increasing attention because of its advantages over bottom-up MS in studying complex proteoforms. TopPIC Suite is a widely used software package for top-down MS-based proteoform identification and quantification. Here, we present the methods for top-down MS data analysis using TopPIC Suite.


Visceral fat mass is always, but adipokines (adiponectin and resistin) are diversely associated with insulin resistance in Chinese type 2 diabetic and normoglycemic subjects.
The present study investigated alteration of abdominal visceral fat mass (VFM) and its relationship to adipokines and insulin resistance (IR) in obese and non-obese type 2 diabetes and normoglycemic subjects. Twenty-two diabetic patients and 37 normoglycemic controls were subgrouped into obese and non-obese according to their BMI. VFM was quantified by computed tomography. Plasma adiponectin and resistin, two adipokines exert contrary effects on insulin sensitivity were measured. Insulin sensitivity was evaluated by an established HOMA model. Obese subjects showed remarkably expanded VFM, while non-obese diabetes obtained more abundant VFM than non-obese controls (104 ± 50 cm(2)vs. 77 ± 26 cm(2), P<0.05). Plasma adiponectin was only significantly decreased in obese diabetes. Plasma resistin was increased in diabetes, but compared between obese and non-obese subjects. Diabetic patients and obese controls were significantly insulin resistant. HOMA-IR index positively correlated to VFM in both groups (r=0.563, P=0.011 for diabetes and r=0.671, P=0.000 for controls). In diabetes but not controls, plasma adiponectin negatively related to VFM (r=-0.687, P=0.000) and HOMA-IR index (r=-0.659, P=0.002), while resistin had no relation to IR and VFM in both groups. Increased VFM may lead to IR by mechanisms beyond adipokines in Chinese type 2 diabetic and normoglycemic subjects.


The ketogenic diet in infants--Advantages of early use.
To evaluate the efficacy and safety of the ketogenic diet (KD) in infants (< 1.5 years of age) compared with older children. Patients with complete follow-up data of ≥ 3 months after initiation of the KD were analyzed retrospectively. Infants < 1.5 years at initiation of the KD (Group A) were compared with children > 1.5 years (Group B). 127 children were screened, 115 (Group A: 58/Group B: 57) were included. There were no significant differences between groups with respect to responder rates (63.8% vs. 57.9% at 3 months), but more infants became seizure free (34.5% vs. 19% at 3 months; 32.7% vs. 17.5% at 6 and 12 months). This result remained stable also after termination of the KD (30.6% vs. 3.9% at last follow-up) (p = 0.000). Looking at infants < 9 months of age separately (n = 42), this result was even stronger with significantly more infants being seizure free at 6 and at 12 months (p = 0.005, p = 0.014, respectively). In addition, a significantly higher number of infants remained seizure free in the long-term (p = 0.001). No group differences between infants and children with respect to safety were observed. Overall 52/115 patients (45.21%) reported side effects, but withdrawal of the KD was only necessary in one infant. Acceptance of the KD was better in infants compared with children at 3 months (0 vs. 14, p = 0.000), but became difficult when solid food was introduced (16 vs. 14; n.s.). According to our results, the KD is highly effective and well tolerated in infants with epilepsy. Seizure freedom is more often achieved and maintained in infants. Acceptance of the diet is better before the introduction of solid food. Therefore, we recommend the early use of the KD during the course of epilepsy.


Pancreatic cancer SLUGged.
In this issue of JEM, Recouvreux et al. (https://doi.org/10.1084/jem.20200388) describe the role of nutrient sensing in the induction of epithelial-mesenchymal transition. Glutamine-deficient pancreatic cancer cells up-regulate classic EMT regulator Slug, providing a link between nutrient stress and metastasis.


Feather mercury concentrations in Southern Ocean seabirds: Variation by species, site and time.
We studied mercury contamination in 25 seabird species breeding along a latitudinal gradient across the Southern Ocean, from Gough Island (40°S) through Marion Island (47°S) to Byers Peninsula (63°S). Total mercury concentrations in body feather samples of adults caught at breeding colonies from 2008 to 2011 were determined. Krill (Euphausia spp.) and other zooplankton consumers had low mercury concentrations (gentoo penguin Pygoscelis papua, chinstrap penguin Pseudomonas Antarctica, common diving petrel Pelecanoides urinatrix, broad-billed prion Pachyptila vittata; mean levels 308-753 ng g(-1)), whereas seabirds consuming squid or carrion had high mercury concentrations (ascending order: Kerguelen petrel Aphrodroma brevirostris, southern giant petrel Macronectes giganteus, soft-plumaged petrel Pterodroma mollis, sooty albatross Phoebetria fusca, Atlantic petrel Pterodroma incerta, northern giant petrel Macronectes halli, great-winged petrel Pterodroma macroptera; 10,720-28038 ng g(-1)). The two species with the highest mercury concentrations, northern giant petrels and great-winged petrels, bred at Marion Island. Among species investigated at multiple sites, southern giant petrels had higher mercury levels at Marion than at Gough Island and Byers Peninsula. Mercury levels among Byers Peninsula seabirds were low, in two species even lower than levels measured 10 years before at Bird Island, South Georgia. Replicate measurements after about 25 years at Gough Island showed much higher mercury levels in feathers of sooty albatrosses (by 187%), soft-plumaged petrels (53%) and Atlantic petrels (49%). Concentrations similar to the past were detected in southern giant petrels at Gough and Marion islands, and in northern giant petrels at Marion. There were no clear indications that timing of moult or migratory behavior affected mercury contamination patterns among species. Causes of inter-site or temporal differences in mercury contamination could not be verified due to a lack of long-term data related to species' diet and trophic levels, which should be collected in future together with data on mercury contamination.


Expression of heme oxygenase-1 in the peripheral blood mononuclear cells from asthmatic patients.
To explore the expression of heme oxygenase-1 (HO-1) in the peripheral blood mononuclear cells (PBMCs) and its relationship with pulmonary ventilation function in asthmatic patients, 18 asthmatic patients and 18 healthy subjects were selected. HO-1 protein and mRNA levels in PBMCs were measured by immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Blood carbon monoxide Hb (COHb), serum total IgE and pulmonary ventilatory function were observed. Our results showed that the percentage of cells positive for immunohistochemical staining of HO-1 were significantly higher in asthmatic patients (41.72 +/- 7.44) % than that in with healthy subjects (10.45 +/- 4.36) % (P < 0.001) and the optical density of PBMC HO-1 mRNA was higher in asthmatic patients (26.05 +/- 4.14) than that in healthy subjects (10. 82 +/- 4.26) (P < 0.001). The relation analysis showed that PBMC HO-1 protein and mRNA levels had significantly negative relation with FEV1%, PEFR, MEFR50%, respectively (r = -0.51-0.89, P < 0.05-0.001, respectively) and a positive relation with COHb and serum total IgE (r = 0.48-0. 85, 0.05-0.001, respectively). It is concluded that the expression of PBMC HO-1 protein and mRNA increased significantly in asthmatic patients, and HO-1 may play a significant role in the pathogenesis of asthma. The expression of HO-1 may bear a relation with severity of asthma.


Anteversion of the acetabulum and femoral neck in early walking age patients with developmental dysplasia of the hip.
Computed tomography measurements were made to quantify the relationship between the anteversion of the acetabulum and femoral neck in 27 early walking age patients (age range; 18-48 months) with developmental dysplasia of the hip. The centre-edge angle and acetabular index were measured in standard pelvis radiographs, and anteversion of acetabulum and femoral neck were measured by use of two-dimensional computed tomography in 25 complete dislocated, 19 subluxated and 10 unaffected hips (a total of 54 hips). The diagnosis of dysplasia, subluxation and complete dislocation of developmental hip dysplasia were determined radiographically using Ishida's criteria. There were statistically significant differences between the three groups for the centre-edge angle, the acetabular index, and acetabulum anteversion. There was no statistically significant difference between the three groups for femoral neck anteversion. The acetabular anteversion was found to be 13.4+/-2.8 degrees (mean+/-SD) in unaffected hips, 16.7+/-1.9 degrees in subluxated hips and 19.8+/-2.5 degrees in complete dislocated hips. There was statistically significant difference between the three groups, with a wide range of acetabular anteversion values noted in all groups (9-26 degrees ). The acetabular anteversion was increased on the dislocated side in each patient and we found no retroverted acetabulum. On the other hand there was no significant difference between the groups with regards to femoral neck anteversion. We conclude that confirming anteversion of the acetabulum and the femoral neck by two-dimensional computed tomography is needed in treatment planning of early walking age patients with developmental hip dysplasia.


The anti-Müllerian hormone (AMH) acts as a gatekeeper of ovarian steroidogenesis inhibiting the granulosa cell response to both FSH and LH.
Anti Müllerian Hormone (AMH) has a negative and inhibitory role in many functions of human granulosa-lutein cells (hGCs) including notoriously the reduction of the aromatase CYP19A1 expression induced by follicle-stimulating hormone (FSH). No data have been provided on the possible role of AMH in modulating the response to luteinizing hormone (LH) (alone or combined with FSH) as well as its effect on other enzymes involved in steroidogenesis including aromatase P450scc. The aim of this study was to investigate the role of AMH as regulator of the basal and stimulated steroids production by hGCs. Primary culture of hGCs were incubated with hormones AMH, LH, and FSH, alone or in combination. The CYP19A1 and P450scc messenger RNA (mRNA) expression, normalized by housekeeping ribosomal protein S7 (RpS7) gene, was evaluated by reverse transcriptase quantitative PCR (RT-qPCR). Each reaction was repeated in triplicate. Negative controls using corresponding amount of vehicle control for each hormone treatment were performed. AMH did not modulate the basal mRNA expression of both aromatase genes at any of the concentrations tested. Meanwhile, the strong mRNA induction of CYP19A1 and P450scc generated by a 24-h gonadotropin treatment (alone and combined) was suppressed by 20 ng/ml AMH added to culture medium. These findings contribute in clarifying the relationship between hormones regulating the early phase of steroidogenesis confirming that AMH is playing a suppressive role on CYP19A1 expression stimulated by gonadotropin in hGCs. Furthermore, a similar inhibitory effect for AMH was observed on P450scc gene expression when activated by gonadotropin treatment.


Pediatric spinal sonography. Part II: Malformations and mass lesions.
The most important spinal disorders in childhood are malformations and mass lesions. The sonographic appearance of the various kinds of dysraphism and their differentiation, of malformations at the cranio-cervical junction, and of mass lesions is demonstrated and illustrated. Based on our preliminary experience, spinal sonography appears to be useful as the first imaging device for the differentiation of complex malformations and as a screening method for occult dysraphism. In mass lesions spinal sonography is useful to diagnose and follow-up disease, with additional imaging procedures currently needed for confirmation of diagnosis.


Referrals for lung transplantation in Japan. Unique indications and necessity of living-donor lobar lung transplantation.
The purpose of this study was to review all referrals to our lung transplant program and to find realistic options for accepted candidates in Japan. During the period from April 1992 to August 1999, 45 referrals were received. After screening, 22 of the referred patients were admitted for an extensive inpatient evaluation, and 15 of these were accepted as candidates for transplantation. The indication was primary pulmonary hypertension in 9, bronchiectasis in 2, lymphangioleiomyomatosis in 2, idiopathic pulmonary fibrosis in 1, and pneumoconiosis in the other 1. Two of those with primary pulmonary hypertension went to the USA and there received bilateral lung transplant. One with bronchiectasis received living-donor lobar lung transplantation in our center. These three recipients are alive and doing well during the follow-up period of 11 to 69 months. Among the 12 patients who have not received lung transplant, 5 patients have died while waiting. Indications for lung transplant are quite distinct in Japan, and primary pulmonary hypertension is the most frequent indication. Living-donor lobar lung transplantation is a realistic option for properly selected candidates.


Stat3 mutations impact on overall survival in large granular lymphocyte leukemia: a single-center experience of 205 patients.
Large granular lymphocyte leukemia (LGLL) is a rare and chronic lymphoproliferative disorder characterized by the clonal expansion of LGLs. LGLL patients can be asymptomatic or develop cytopenia, mostly neutropenia. Somatic STAT3 and STAT5b mutations have been recently reported in approximately 40% of patients. The aim of this study is to analyze clinical and biological features of a large cohort of LGLL patients to identify prognostic markers affecting patients' outcome. In 205 LGLL patients, neutropenia (ANC < 1500/mm3) was the main feature (38%), with severe neutropenia (ANC < 500/mm3) being present in 20.5% of patients. STAT3 mutations were detected in 28.3% patients and were associated with ANC < 500/mm3 (p < 0.0001), Hb < 90 g/L (p = 0.0079) and treatment requirement (p < 0.0001) while STAT5b mutations were found in 15/152 asymptomatic patients. By age-adjusted univariate analysis, ANC < 500/mm3 (p = 0.013), Hb < 90 g/L (p < 0.0001), treatment requirement (p = 0.001) and STAT3 mutated status (p = 0.011) were associated to reduced overall survival (OS). By multivariate analysis, STAT3 mutated status (p = 0.0089) and Hb < 90 g/L (p = 0.0011) were independently associated to reduced OS. In conclusion, we identified clinical and biological features associated to reduced OS in LGLL and we demonstrated the adverse impact of STAT3 mutations in patients' survival, suggesting that this biological feature should be regarded as a potential target of therapy.


Caffeine alters the breathing pattern during high-intensity whole-body exercise in healthy men.
The current study investigated the effect of caffeine on the breathing pattern during a high-intensity whole-body exercise. Using a randomized, crossover, counterbalanced, and double-blind design, twelve healthy men ingested either 5 mg.kg-1 of caffeine or cellulose (placebo) one hour before performing a high-intensity whole-body exercise (i.e., work rate corresponding to 80% of the difference between the gas exchange threshold and maximal oxygen uptake) until the limit of tolerance. Ventilatory and metabolic responses were recorded throughout the trial and at task failure. Caffeine ingestion increased time to task failure in relation to the placebo (368.1 ± 49.6 s vs. 328.5 ± 56.6 s, p = 0.005). Caffeine also increased tidal volume and inspiratory time throughout the exercise (p < 0.05). Compared to task failure with placebo, task failure with caffeine intake was marked by higher (p < 0.05) minute ventilation (134.8 ± 16.4 vs. 147.6 ± 18.2 L.min-1), the ventilatory equivalent of oxygen consumption (37.8 ± 4.2 vs. 41.7 ± 5.5 units), and respiratory exchange ratio (1.12 ± 0.10 vs. 1.19 ± 0.11 units). In conclusion, ingestion of caffeine alters the breathing pattern by increasing tidal volume and lengthening the inspiratory phase of the respiratory cycle. These findings suggest that caffeine affects the ventilatory system, which may account, in part, for its ergogenic effects during high-intensity whole-body exercises.


Axillary surgery among estrogen receptor positive women 70 years of age or older with clinical stage I breast cancer, 2004-2010: a report from the National Cancer Data Base.
Randomized trials have not demonstrated a survival benefit for axillary dissection in the elderly, but the use of axillary staging for women 70 years of age and older remains controversial. We utilized the National Cancer Data Base to study the use of axillary staging from 2004 to 2010 on 102,026 clinically node-negative and estrogen receptor-positive cases of pT1N0 tumors. Chi-square and logistic regression models were used to determine the trends and factors related to axillary staging. Axillary nodes were examined in 88.9 % of the total cohort, and the trend significantly increased from 87.7 % in 2004 to 89.2 % in 2010. A total of 77.2 % of patients underwent lumpectomy and 22.8 % mastectomy, with 87.0 % of lumpectomy patients undergoing axillary staging compared to 95.5 % of mastectomy patients. Predictors of axillary staging examined were age, comorbidity, income, histology, grade, facility type, facility location, and population density. The strongest independent predictor of axillary staging was age: 96.0 % of women aged 70-75 years underwent axillary staging, versus 92.3 % of women 75-80 years old, 83.2 % of women 80-85 years old, 66.5 % of women 86-90 years old, and 45.6 % of women >90 years old. Patients treated at academic/research facilities were 18.5 % less likely (odds ratio 0.81, 95 % confidence interval 0.76-0.87) than community cancer programs to undergo axillary staging. There was significant regional variation among U.S. Census regions: patients treated in the Midwest were 3.8 times more likely to undergo axillary staging than those treated in the Northeast. Despite data indicating decreased utility, axillary staging remains overutilized in women with advancing age.


The effect of follow-up blood cultures on mortality and antibiotic use in gram-negative bloodstream infections.
Gram-negative bloodstream infections (GN-BSIs) are a significant clinical challenge. The utility of follow-up blood cultures (FUBCs) in GN-BSIs and their impact on mortality and antibiotic consumption are areas of debate. This study aimed to evaluate the effect of FUBCs on mortality and antibiotic consumption in patients with GN-BSIs. This single-center, retrospective study was conducted in aged > 18 years of patients with GN-BSIs. FUBC was defined as a blood culture performed 2-7 days after the first blood culture. Patients were grouped as FUBC and no FUBC and compared. A 1:1 match analysis was performed between the groups according to the SOFA score. The matched subgroup was compared for mortality risk factors with logistic regression models. The two groups were compared for the duration of effective antibiotic therapy and total antibiotic consumption (days of therapy per 1000 patient days (DOT/1000 PD)). FUBC was performed in 564 (69.4%) of 812 patients. Persistent, positive and negative FUBC rates were 7.9%, 14%, and 78%, respectively. The frequency of persistent GN-BSI in patients with appropriate antibiotic therapy was 3.9%. SOFA score (OR:1.33; 95% CI, 1.23-1.44), Charlson comorbidity index score (OR:1.18; 95% CI, 1.08-1.28), hospital-acquired infections (OR:1.93; 95% CI, 1.08-3.46) and carbapenem-resistant GN-BSI (OR: 2.92; 95% CI, 1.72-4.96) were independent risk factors for mortality. No relationship was found between FUBC and mortality (p > 0.05). Duration of effective antibiotic therapy (10(4-16) vs. 15(9-20), p < 0.001) and DOT/1000 PD (1609 (1000-2178) vs. 2000 (1294-2769), p < 0.001) were longer in the FUBC group. Routine FUBC should not be recommended because of the low prevalence of persistent infections in patients under appropriate antibiotic therapy and FUBC increases antibiotic consumption.


Effect of flow on hydraulic conductivity and reflection coefficient of rabbit mesentery.
To measure the hydraulic conductivity and reflection coefficient for albumin, as defined by the Starling equation, in rabbit mesentery. A section of rabbit mesentery was fixed between two chambers filled with lactated Ringer solution. Flow (Q) of Ringer solution was measured across the mesentery at driving pressures (delta P) between 1 and 6 cm H2O. Hydraulic conductivity was proportional to the slope of the Q-delta P curve. At constant delta P (approximately -2, -4, or -6 cm H2O), flow was measured at three different albumin concentration differences (0.5, 1, and 1.5 g/dl). Unstirred layer effects were minimized by magnetic stirrers. Reflection coefficient was the negative of the slope of the Q-delta pi curve divided by the slope of the Q-delta P curve, where delta pi was the albumin osmotic pressure difference. Hydraulic conductivity was measured before and after testicular hyaluronidase was added to the Ringer solution. There was no significant difference in conductivity per unit area (Lp) for the three different driving pressures. Hyaluronidase increased hydraulic conductivity significantly (p < 0.01) by 72 +/- 56%, indicating that hyaluronan and other glycosaminoglycans contributed to tissue fluid resistance. Reflection coefficient (sigma) increased from 0.02 to 0.14 as flow increased eightfold. The results suggest that the mesentery tissue provides little restriction to the passage of albumin. The increase in conductivity in the presence of hyaluronidase indicates that tissue hyaluronan and other glycosaminoglycans provide fluid resistance to bulk flow.


Atmospheric chemical composition of bulk deposition at two geographically distinct locations in Sri Lanka.
This study presented the research work carried out for the investigation of chemical composition of bulk precipitation in two geographically and economically distinct areas, namely Gampaha and Kandy Districts. This study was conducted from 2013 to 2014 at three sampling stations in each District. The bulk precipitation was analyzed for pH, conductivity, Na+, NH4+, K+, Mg2+, Ca2+, F-, Cl-, NO3-, SO42-, Pb, Cu, Mn, Al, Zn and Fe for a total of 375 samples. Only 8% events of acidic precipitation were recorded in Gampaha District when compared with 3% in Kandy District. The volume weighted average concentrations of the major ionic species present in precipitation samples were in the order of Na+ > Ca2+ > Cl- > NH4+ > SO42- > Mg2+ > NO3- > K+ > F- in the Gampaha stations, while the order was NH4+ > Ca2+ > Na+ > Cl- > SO42- > Mg2+ > NO3- > K+ > F- in Kandy District. Neutralization of acidity of precipitation is much more related to CaCO3 than NH3, and high content of Ca2+ ions present in both Districts strongly supports this fact. When considering marine contribution, SO42-/Na+, Ca2+/Na+ and Mg2+/Na+ ratios are higher than the reference value suggesting contribution of sources other than marine. Depositions of both Districts show that the concentration of Al is the highest while that of Mn is the lowest. Principal component analysis suggests that influencing human activities on chemical composition of rain water depends on thermal power plant, oil refinery, heavy traffic and waste incineration in the study area.


Fungi associated with the southern pine beetle: avoidance of induced defense response in loblolly pine.
Loblolly pines (Pinus taeda) are rapidly killed by colonizing southern pine beetle (Dendroctonus frontalis). The female beetles carry two species of fungi (Ceratocystis minor var. barrasii and an unnamed basidiomycete) within a mycangium. The insects are also frequently associated with a blue-staining form of C. minor. These fungi are inoculated into the tree during colonization. The tree has an induced defensive response that involves resin soaking and necrosis of affected tissue isolating the invading organlsms. The blue-staining fungus stimulates formation of this response in the tree, but the two mycangial fungi do not. These results suggest that the beetles are closely associated with two highly pathogenic fungi that do not stimulate one of the critical components of tree defense.


Distribution of laminin in the murine pituitary.
The distribution and cellular localization of the glycoprotein laminin were investigated by light and electron microscopic immunocytochemistry in the adult murine pituitary gland. Immunoblots confirmed that laminin was the only protein in the pituitary gland of the adult male mouse to react with antilaminin serum. Laminin immunoreactivity was demonstrated at the light microscopic level simultaneously with that of beta-follicle stimulating hormone (beta-FSH) and beta-luteinizing hormone (beta-LH). In addition to its distribution is basal laminae, laminin immunoreactivity was coincidently expressed in gonadotrophs with the immunoreactivities of beta-FSH and beta-LH. Electron microscopic immunocytochemistry was employed on aldehyde-fixed sections embedded in L.R. White. Sites of binding of primary antisera to laminin were identified with affinity-purified secondary antisera directly coupled to 20 nm particles of colloidal gold. Three antisera recognizing laminin were compared and found to result in an identical pattern of immunoreactivity. Laminin was found extracellularly only in formed basal laminae in all three lobes of the pituitary and was not found in extracellular matrices of connective tissue. Laminin immunoreactivity was also found intracellularly in gonadotrophs but in none of the other endocrine or non-endocrine cells of the anterior lobe. Within gonadotrophs, only secretory granules were labeled. The majority, but not all, secretory granules were labeled in each of the gonadotrophs examined, and the proportion of granules labeled with laminin could not be increased by doubling the concentration of anti-laminin serum. Laminin immunoreactivity segregated with the subset of secretory granules containing beta-FSH. In contrast, laminin immunoreactivity was absent in the smaller subset of secretory granules that contain serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)


A comparison of epidural versus general anesthesia for outpatient endoscopic preperitoneal herniorrhaphy.
To study the efficacy of epidural versus general anesthesia on length of stay, patient recovery and anesthetic-related complications in patients undergoing endoscopic preperitoneal herniorrhaphy. One hundred sixty-seven consecutive patients undergoing endoscopic preperitoneal herniorrhaphy from July, 1994, to August, 1995, were retrospectively studied. A total of 243 herniorrhaphies were performed. Four patients required conversion of epidural anesthesia to general anesthesia because of inadequate sensory blockade (67/71; 94% success rate). One-hundred-forty-eight patients were available for review. Sixty-seven patients underwent successful epidural anesthesia during the case, while 81 patients were managed with general anesthesia. Thirty patients (37%) receiving general anesthesia required interventions for nausea compared to only six patients (9.0%) in the epidural anesthesia group (p < 0.001). Thirty patients (37%) in the general anesthesia group required intervention because of complaints of pain, compared to 13 (19.4%) in the epidural group (p < 0.05). There were no differences between the two groups for length of stay in OR, PACU, or total hospital times. The use of epidural anesthesia during the performance of endoscopic preperitoneal herniorrhaphy was associated with a decrease in the incidence of postoperative pain and nausea. The technique was successful in 94% of the cases in which it was used. Epidural anesthesia is recommended as an effective alternative to general anesthesia for the performance of outpatient endoscopic preperitoneal herniorrhaphy.


On the recall of vestibular sensations.
Functional neuroimaging studies on the recall or imagination of a distinctive task in the motor network or of sensations in sensory systems (visual, acoustic, nociceptive, gustatory, and olfactory) demonstrated that the respective primary cortex is often involved in the mental imagery process. Our aim was to examine this phenomenon in the vestibular system using fMRI. Sixteen healthy subjects were asked to remember the feeling of a rotatory chair procedure in contrast to an identical situation at rest. Shortly afterwards they were asked to recall the vestibular experience in a 1.5-T scanner. The resulting activations were then compared with the responses of a galvanic vestibular control experiment and a rest condition. The vestibular recall showed significant bihemispheric activations in the inferior frontal gyri, the anterior operculum, the middle cingulate, the putamen, the globus pallidus, the premotor motor cortex, and the anterior insula. We found activations in regions known to play a role in spatial referencing, motor programs, and attention in the recall of vestibular sensations. But important known relay stations for the cortical processing of vestibular information showed neither relevant activations nor deactivations.


Anionic stitching polymerization of styryl(vinyl)silanes for the synthesis of sila-cyclic olefin polymers.
Anionic stitching polymerization of styryl(vinyl)silanes has been developed for the synthesis of a new type of silicon- and carbon-containing polymer possessing fused sila-bicyclic structures in the main chain. The obtained polymers were found to be thermally stable with relatively high glass-transition temperatures and highly transparent in the visible light region.


Wetland Entitlement and Sustainable Livelihood of Local Users in Bangladesh: A Case Study of Hakaluki Haor Communities.
Local wetland-dependent communities in Bangladesh face numerous challenges in attaining sustainable livelihoods. To understand this phenomenon, it is imperative to explore the factors that prevent them from acquiring the necessary endowments for livelihood sustainability. Notably, literature exploring these is very scant. Using the Entitlement Theory proposed by Amartya Sen, we analyzed how the wetland management and policy of Bangladesh affected the legal entitlement and livelihood endowments of local wetland-dependent communities. Hakaluki Haor, Bangladesh, was selected as a case. Primary data were collected from four groups of participants, namely local users, local and national level administrative officials, officials of non-government organizations, and experts on environment and natural resources. A total of 31 interviews were conducted using a semi-structured interview schedule. Our findings reveal that both intrinsic limitations and implementation barriers of the wetland management policy barred many users from attaining legal entitlement to wetland resources. We observed that users' limited entitlement to resources impeded their access to at least four types of livelihood endowments, namely the natural, financial, human, and social, required for a sustainable livelihood.


Affect, corporeality and the limits of belonging: breastfeeding in public in the contemporary UK.
The UK has some of the lowest breastfeeding duration rates in the industrialised world. This paper considers women's experiences breastfeeding in public as a factor in breastfeeding duration. Research is based on an analysis of: 11 interviews and a 46-person survey of new mothers in Southampton, Hampshire; 180 postings about breastfeeding in public on UK parenting website mumsnet; and a patent application for a 'portable lactation module'. I analyse these data through an engagement with the work of cultural theorist Sara Ahmed to argue that the 'limits of sociability' in public space in the UK can be marked through affective practice. This paper makes three unique contributions to scholarship. First, it increases understanding regarding an issue of direct importance to health policy by filling a gap in knowledge about women's experiences breastfeeding outside the home in the UK. Second, it contributes to the field of health geography by showing how affective environments can constrain health-promoting behaviours. Third, it extends conceptual work in human geography more broadly through an analysis of the relationships between affect, embodiment and urban subjectivity.


Peptides, the limbic lobe and schizophrenia.
The human brain contains several peptides with probable synaptic actions, some of which form complex neuronal networks in the limbic lobe (amygdala, hippocampus and temporal cortex). A limbic lobe abnormality has been postulated in schizophrenia on the basis of similarities between schizophrenic symptoms and symptoms in cases of known limbic pathology. Cholecystokinin (CCK), somatostatin (SRIF), neurotensin (NT), vasoactive intestinal polypeptide (VIP) and substance P (SP)-like immunoreactivities were measured by radioimmunoassay in 10 brain areas of 14 schizophrenics and 12 controls. In the schizophrenic group symptoms had been rated in life and the group was divided into Type I (n = 7) and Type II (n = 7) subgroups on the basis of the absence or presence of morbid negative symptoms. In control brains each peptide showed a characteristic distribution with high levels in cortex (CCK), limbic lobe (SOM, NT, VIP) or striatal areas (SP) and low levels of each of the peptides in thalamus. Significant (P less than 0.05) differences between groups were: reductions of CCK and SOM in hippocampus and CCK in amygdala in Type II schizophrenics, and CCK in the temporal cortex of the total schizophrenic group; and elevations of VIP in amygdala in Type I schizophrenics and of SP in the hippocampus in the total schizophrenic group. The findings could not be explained by variables such as age, delay between death and necropsy or to neuroleptic medication. These clinical-state related alterations in the peptide content of the limbic system in schizophrenia may illuminate the pathophysiological basis of the disease, particularly the distinction between Type I and II syndromes.


Contribution of Extensive Farming Practices to the Supply of Floral Resources for Pollinators.
Intensification of agricultural practices leads to a loss of floral resources and drives pollinator decline. Extensive agricultural practices are encouraged in Europe and contribute to the preservation of biodiversity. We compared three agricultural landscapes without extensive farming practices with three adjacent landscapes containing organic crops and extensively managed grasslands in Belgium. Nectar resource availability and plant-pollinator interactions were monitored from April to June. Flower density per plant species and plant-pollinator interactions were recorded in different landscape elements. In April, the main nectar resources were provided by linear elements such as hedgerows and forest edges. Nectar production peaked in May, driven by intensive grasslands and mass-flowering crops. Occurrence of extensive grasslands and organic crops significantly alleviated the nectar resource gap observed in June. Our results underscore the importance of maintaining landscape heterogeneity for continuous flower resources and highlight the specific role of extensive grasslands and organic crops in June.


Patterns, treatments, and prognosis of tumor recurrence after resection for hepatocellular carcinoma with microvascular invasion: a multicenter study from China.
Microvascular invasion (MVI) is a risk factor of post-hepatectomy tumor recurrence for hepatocellular carcinoma (HCC). The patterns, treatments, and prognosis have not been documented in HCC patients with MVI. A multicenter database of patients with HCC and MVI following resection was analyzed. The clinicopathological and initial operative data, timing and first sites of recurrence, recurrence management, and long-term survival outcomes were analyzed. Of 1517 patients included, the median follow-up was 39.7 months. Tumor recurrence occurred in 928 patients, with 49% within 6 months of hepatectomy and 60% only in the liver. The incidence of intrahepatic only recurrence gradually increased with time after 6 months. Patients who developed recurrence within 6 months of hepatectomy had worse survival outcomes than those who developed recurrence later. Patients who developed intrahepatic only recurrence had better prognosis than those with either extrahepatic only recurrence or those with intra- and extrahepatic recurrence. Repeat resection of recurrence with curative intent resulted in better outcomes than other treatment modalities. Post-hepatectomy tumor recurrence in patients with HCC and MVI had unique characteristics and recurrence patterns. Early detection of tumor recurrence and repeat liver resection with curative intent resulted in improved long-term survival outcomes.


Targeting Chronic Inflammation of the Digestive System in Cancer Prevention: Modulators of the Bioactive Sphingolipid Sphingosine-1-Phosphate Pathway.
Incidence of gastrointestinal (GI) cancers is increasing, and late-stage diagnosis makes these cancers difficult to treat. Chronic and low-grade inflammation are recognized risks for most GI cancers. The GI mucosal immune system maintains healthy homeostasis and signalling molecules made from saturated fats, bioactive sphingolipids, play essential roles in healthy GI immunity. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid, is a key mediator in a balanced GI immune response. Disruption in the S1P pathway underlies systemic chronic metabolic inflammatory disorders, including diabetes and GI cancers, providing a strong rationale for using modulators of the S1P pathway to treat pathological inflammation. Here, we discuss the effects of bioactive sphingolipids in immune homeostasis with a focus on S1P in chronic low-grade inflammation associated with increased risk of GI carcinogenesis. Contemporary information on S1P signalling involvement in cancers of the digestive system, from top to bottom, is reviewed. Further, we discuss the use of novel S1P receptor modulators currently in clinical trials and their potential as first-line drugs in the clinic for chronic inflammatory diseases. Recently, ozanimod (ZeposiaTM) and etrasimod have been approved for clinical use to treat ulcerative colitis and eosinophilic oesophagitis, respectively, which may have longer term benefits in reducing risk of GI cancers.


Rupatadine 10 mg in the treatment of immediate mosquito-bite allergy.
People frequently experience wealing and delayed papules from mosquito bites. Wealing is mediated by antisaliva IgE antibodies and histamine. Rupatadine is a new antihistamine effective in allergic rhinitis and urticaria, but the effect on mosquito-bite allergy is not known. To determine the effectiveness of rupatadine in inmediate mosquito-bite allergy-confirmed adult patients. A double-blind, placebo-controlled, cross-over study was performed with rupatadine 10 mg and matched placebo in 30 mosquito-bite-sensitive adults. The mean age was 37 years and the subjects had suffered from harmful mosquito bites for a mean of 15 years. Either rupatadine or placebo was taken at 08:00 am for 4 days, followed by a 5 day wash out period and then alternative treatment was given for 4 days. On day 3, in both drug periods the subjects received two Aedes aegypti mosquito-bites on the forearm. The size of lesions and intensity of pruritus [visual analogue scale (VAS)] were measured after 15 min bite reaction. Twenty-six subjects were analysed for efficacy. The size of the 15 min bite reaction under placebo was of 106 mm2 and under rupatadine, of 55 mm2. This is a significant decrease (48%; P=0.0003). The accompanying pruritus decreased from 60 (VAS; median) under placebo to 47.5 under rupatadine, which also is a significant (P=0.019) difference. There was no significant (P=0.263) difference in adverse events under rupatadine and placebo. The present placebo-controlled study in mosquito-bite-sensitive adults shows that rupatadine 10 mg prophylactically given is an effective treatment for the mosquito-bite wealing and skin pruritus.


Nerve growth factor induces angiogenic activity in a mouse model of hindlimb ischemia.
Recent studies suggest that nerve growth factor (NGF), a neurotrophic factor known to play a crucial role in neurite growth and differentiation, may also modulate vascular cell functions. In the present study, it was investigated whether NGF exhibits an angiogenic effect in a mouse model of hindlimb ischemia induced by femoral artery occlusion. Enzyme-linked immunosorbent assay determination revealed an enhanced endogenous NGF production (378 +/- 100 and 54 +/- 26 pg/g tissue in 7 day ischemic and normoperfused adductor muscles, respectively; P<0.05). Furthermore, exogenous NGF, administered subcutaneously for 7 days in ischemic hindlimb, induced a marked increase of arteriole length density (NGF =41 +/- 5 vs. Saline=22 +/- 4 mm/mm(3); P<0.05). However, capillaries were not significantly increased (NGF =1035 +/- 182 vs. Saline= 829 +/- 60 mm/mm(3); P>0.05). In conclusion, the present study provides first evidence that NGF exerts angiogenic properties in vivo.


Two cases of Cushing's syndrome due to overuse of topical steroid in the diaper area.
Topical use of corticosteroids may cause immunosuppression and iatrogenic Cushing's syndrome via hypothalamic-pituitary-adrenal axis. We report two cases with iatrogenic Cushing's syndrome with different clinical outcomes due to abuse of same potent topical steroid clobetasol propionate. One of them died because of fatal disseminated cytomegalovirus infection. The other patient recovered completely. Physicians and parents should be informed about the adverse effects of such potent topical corticosteroids and physicians should prescribe less potent agents, especially during infancy.


Measuring the effects of Compactness/Sprawl on COVID 19 spread patterns at the neighborhood level.
This study analyzes the compactness/sprawl index and its effects on the spread of COVID-19 in the neighborhoods of Ahvaz, Iran. Multiple Criteria Decision Making and GIS techniques were used to develop the index. Also, the effects of compactness/sprawl on COVID-19 were investigated using a regression model. It was found that when considering the number of COVID-19 cases per 1000 people, the compactness/sprawl index did not affect the spread of the disease. However, it had a low but significant effect if the raw number of cases was considered. Results also showed that the compactness index significantly affected the raw number of cases, with a coefficient of 0.291, indicating that more compact neighborhoods had more COVID-19 cases. This is unsurprising as more people live in compact areas and, therefore, the raw number of cases is also likely to be higher. In the absence of proper control measures, this could result in further contact between people, thereby, increasing the risk of virus spread. Overall, we found that compactness had a dual effect on the spread of COVID-19 in Ahvaz. We conclude that proper development and implementation of control measures in well-designed compact neighborhoods are essential for enhancing pandemic resilience.


Ultrasound-guided selective peripheral nerve block compared with the sub-dissociative dose of ketamine for analgesia in patients with extremity injuries.
To compare the analgesic efficacy of ultrasound-guided selective peripheral nerve block (PNB) and sub-dissociative dose ketamine (SDK) for management of acute pain in patients with extremity injuries presenting to the emergency department (ED). This prospective, open-label randomized clinical trial was conducted in the ED of a tertiary care Institute. The patients were provided with either ultrasound-guided selective PNB or SDK. The primary outcome was a reduction in pain in numerical rating scale (NRS) by at least 3 points without rescue analgesia. The secondary outcomes were the need for rescue analgesia, adverse events, and patient satisfaction on either arm. A total of 111 patients with isolated traumatic extremity injuries were included in the final analysis. The NRS score was significantly lower in the PNB group compared to the SDK group at 30, 60,120, 180-, and 240-min post-intervention [group ∼ time interaction, F (5, 647) = 21.53, p ≤ 0.001]. All the patients in the PNB group exhibited primary outcome (NRS ≥3 reductions) at 30 min post-intervention compared with 36 (65%) in the SDK group [-1.02(-1.422,0.622)]. Rescue analgesia was required in 10 (18%) patients in the SDK group compared to none in the PNB group [0.663(0.277,1.050)]. The decrease in NRS score from baseline at 30 min was significantly higher in PNB groups compared to the SDK group [-2.166(-2.640, -1.692)]. The most common side effect reported in the SDK group was dizziness 35(64%), followed by nausea 15(27%). None of the patients in the PNB group reported any complications. Patient satisfaction was higher in the PNB group than SDK group. The study provides evidence that ultrasound-guided PNB is superior to SDK in terms of its analgesic efficacy in the management of acute pain due to extremity injuries and is associated with higher patient satisfaction. The need for rescue analgesia was significantly less in the PNB group. SDK was associated with a high incidence of dizziness and nausea.


Prediction of burden and management of renal calculi from whole kidney radiomics: a multicenter study.
To assess if autosegmentation-assisted radiomics can predict disease burden, hydronephrosis, and treatment strategies in patients with renal calculi. The local ethical committee-approved, retrospective study included 202 adult patients (mean age: 53 ± 17 years; male: 103; female: 99) who underwent clinically indicated, non-contrast abdomen-pelvis CT for suspected or known renal calculi. All CT examinations were reviewed to determine the presence (n = 123 patients) or absence (n = 79) of renal calculi. On CT images with renal calculi, each kidney stone was annotated and measured (maximum dimension, Hounsfield unit (HU), and combined and dominant stone volumes) using a HU threshold-based segmentation. We recorded the presence of hydronephrosis, number of renal calculi, and treatment strategies. Deidentified CT images were processed with the radiomics prototype (Radiomics, Frontier, Siemens Healthineers), which automatically segmented each kidney to obtain 1690 first-, shape-, and higher-order radiomics. Data were analyzed using multiple logistic regression analysis with areas under the curve (AUC) as output. Among 202 patients, only 28 patients (18%) needed procedural treatment (lithotripsy or ureteroscopic stone extraction). Gray-level co-occurrence matrix (GLCM) and gray-level run length matrix (GLRLM) differentiated patients with and without procedural treatment (AUC 0.91, 95% CI 0.85-0.92). Higher-order radiomics (gray-level size zone matrix - GLSZM) differentiated kidneys with and without hydronephrosis (AUC: 0.99, p < 0.001) as well those with different stone volumes (AUC up to 0.89, 95% CI 0.89-0.92). Automated segmentation and radiomics of entire kidneys can assess hydronephrosis presence, stone burden, and treatment strategies for renal calculi with AUCs > 0.85.


Cerebral lactate release after circulatory arrest but not after low flow in pediatric heart operations.
Arteriovenous (jugular bulb) differences in blood lactate were followed throughout the procedure and until 18 hours postoperatively in 17 children undergoing congenital heart operations during profound hypothermia. Transcranial Doppler sonography was used to monitor changes in blood flow velocity in the middle cerebral artery. Ten children had a period of total circulatory arrest (39 +/- 6 minutes) during profound hypothermia (arrest group). Another 7 children had continuous but reduced pump flow (0.6 to 1.2 L/m2) throughout hypothermic cardiopulmonary bypass (low-flow group). The mean age was 7.3 +/- 1.3 months in the arrest group and 7.9 +/- 2.2 months in the low-flow group. The mean time on bypass was 90 +/- 10 minutes in the arrest group and 75 +/- 9 minutes in the low-flow group. The velocity of blood flow in the middle cerebral artery decreased significantly (p < 0.05) in both groups to less than 50% of the preoperative level during hypothermia and increased during and after rewarming. Differences in blood lactate level were significantly less than zero (p < 0.05) from the start of rewarming until 3 hours after the end of cardiopulmonary bypass in the arrest group, whereas differences in blood lactate level remained close to zero in the low-flow group. We conclude that circulatory arrest during profound hypothermia is followed by a period with release of lactate from the brain, indicating anaerobic cerebral metabolism and possibly disturbed cerebral aerobic metabolism. This study argues for the avoidance of circulatory arrest whenever possible.


A case of seminal vesicle cyst associated with ipsilateral renal agenesis diagnosed during an investigation of perineal pain.
A 38-year-old man was referred to our hospital with perineal and micturition pain. Transrectal ultrasound (TRUS) revealed a cystic mass in the outer prostate. Pelvic cyst and left renal agenesis were confirmed by magnetic resonance imaging (MRI) and computerized tomography (CT), and we diagnosed seminal vesicle cyst. The symptoms have since subsided, the possibility of sterility has been ruled out, and the patient is showing good improvement.


Inducing drop to bubble transformation via resonance in ultrasound.
Bubble formation plays an important role in industries concerned with mineral flotation, food, cosmetics, and materials, which requires additional energy to produce the liquid-gas interfaces. A naturally observed fact is, owing to the effect of surface tension, a bubble film tends to retract to reduce its surface area. Here we show a "reverse" phenomenon whereby a drop is transformed into a bubble using acoustic levitation via acoustic resonance. Once the volume of the cavity encapsulated by the buckled film reaches a critical value V*, resonance occurs and an abrupt inflation is triggered, leading to the formation of a closed bubble. Experiments and simulations both reveal that V* decreases with increasing acoustic frequency, which agrees well with acoustic resonance theory. The results afford enlightening insights into acoustic resonance and highlight its role in manipulating buckled fluid-fluid interfaces, providing a reference for fabricating unique core-shell-like materials.


Diagnostic reference levels for chest computed tomography in children as a function of patient size.
Radiation exposures from computed tomography (CT) in children are inadequately studied. Diagnostic reference levels (DRLs) can help optimise radiation doses. To determine local DRLs for paediatric chest CT performed mainly on modern dual-source, multi-slice CT scanners as a function of patient size. Five hundred thirty-eight chest CT scans in 345 children under 15 years (y) of age (median age: 8 y, interquartile range [IQR]: 4-13 y) performed on four different CT scanners (38% on third-generation and 43% on second-generation dual-source CT) between November 2013 and December 2020 were retrospectively analysed. Examinations were grouped by water-equivalent diameter as a measure of patient size. DRLs for volume CT dose index (CTDIvol) and dose-length product (DLP) were determined for six different patient sizes and compared to national and European DRLs. The DRLs for CTDIvol and DLP are determined for each patient size group as a function of water-equivalent diameter as follows: (I) < 13 cm (n = 22; median: age 7 months): 0.4 mGy, 7 mGy·cm; (II) 13 cm to less than 17 cm (n = 151; median: age 3 y): 1.2 mGy, 25 mGy·cm; (III) 17 cm to less than 21 cm (n = 211; median: age 8 y): 1.7 mGy, 44 mGy·cm; (IV) 21 cm to less than 25 cm (n = 97; median: age 14 y): 3.0 mGy, 88 mGy·cm; (V) 25 cm to less than 29 cm (n = 42; median: age 14 y): 4.5 mGy, 135 mGy·cm; (VI) ≥ 29 cm (n = 15; median: age 14 y): 8.0 mGy, 241 mGy·cm. Compared with corresponding age and weight groups, our size-based DRLs for DLP are 54% to 71% lower than national and 23% to 85% lower than European DRLs. We developed DRLs for paediatric chest CT as a function of patient size with substantially lower values than national and European DRLs. Precise knowledge of size-based DRLs may assist other institutions in further dose optimisation in children.


Relationship between schizotypal and borderline traits in college students.
The main objective of the present investigation was to analyze the relationship between self-reported schizotypal and borderline personality traits in a sample of 759 college students (M = 19.63 years; SD = 2.03). For this purpose, the Schizotypal Personality Questionnaire-Brief (SPQ-B; Raine and Benishay, 1995) and Borderline Personality Questionnaire (BPQ; Poreh et al., 2006) were administered. The results showed that schizotypal and borderline features are partially related at subclinical level. The exploratory factor analysis conducted on the subscales revealed a three-factor solution comprised of the following factors: Identity/Interpersonal, Lack of Control and Schizotypal. The canonical correlation analysis showed that schizotypal features and borderline personality traits shared 34.8% of the variance. The data highlight the overlap between schizotypal and borderline personality traits in nonclinical young adults. Future studies should continue to examine the relationship and the degree of overlap between these traits in community samples.


Revision of the driver behavior questionnaire for Chinese drivers' aberrant driving behaviors using naturalistic driving data.
The Manchester Driver Behavior Questionnaire (DBQ) is a widely used self-reported measure of aberrant driving behaviors. It provides a standardized way of evaluating drivers' safety awareness and motivation, but the effectiveness of the DBQ's application in different regions can be influenced by culture, social norms, and time period. Several studies have adjusted DBQ items to reflect driver behavior native to particular regions or times, but few have used objective measurements to make proper adjustments. A naturalistic driving study (NDS) provides vehicle kinematic data and in-vehicle videos that objectively capture actual driving behaviors. The gender, age, and driving experience characteristics of aberrant driving behaviors were analyzed, and, based on comparisons between the DBQ self-reported driving behaviors and those observed in the Shanghai, China, NDS, the existing items from the Manchester DBQ were subsequently adjusted. Sixty-two types of real-world aberrant driving behaviors were extracted from 490 valid crash and near crash events observed in the Shanghai NDS. Aberrant driving behavior rates were calculated for individual characteristics (gender, age, and driving experience), and factor rates were calculated based on the three DBQ factor types of violation, error, and lapse. Results revealed that (a) male drivers, drivers in their thirties, and those with three to five years of driving experience demonstrated higher rates of aberrant driving behaviors; and (b) there were weak correlations between observed NDS factor rates and self-reported DBQ scores, and only slight differences among drivers divided by factor rate level (e.g., high violation rate). The questionnaire calibrated for Chinese drivers includes 23 items. Five of the original 24 DBQ items were modified, eight were left unchanged, eleven were deleted, and ten field-observed combined behaviors were added. In addition to the importance of adjusting the DBQ for today's Chinese drivers, this study provides a method for objectively modifying DBQ items in the future in accord with observed driving behaviors in an NDS.


Impact of daily caffeine intake and timing on electroencephalogram-measured sleep in adolescents.
Caffeine use is ubiquitous among adolescents and may be harmful to sleep, with downstream implications for health and development. Research has been limited by self-reported and/or aggregated measures of sleep and caffeine collected at a single time point. This study examines bidirectional associations between daily caffeine consumption and electroencephalogram-measured sleep among adolescents and explores whether these relationships depend on timing of caffeine use. Ninety-eight adolescents aged 11-17 (mean =14.38, standard deviation = 1.77; 50% female) participated in 7 consecutive nights of at-home sleep electroencephalography and completed a daily diary querying morning, afternoon, and evening caffeine use. Linear mixed-effects regressions examined relationships between caffeine consumption and total sleep time, sleep-onset latency, sleep efficiency, wake after sleep onset, and time spent in sleep stages. Impact of sleep indices on next-day caffeine use was also examined. Increased total caffeine consumption was associated was increased sleep-onset latency (β = .13; 95% CI = .06, .21; P < .001) and reduced total sleep time (β = -.17; 95% confidence interval [CI] = -.31, -.02; P = .02), sleep efficiency (β = -1.59; 95% CI = -2.51, -.67; P < .001), and rapid eye movement sleep (β = -.12; 95% CI = -.19, -.05; P < .001). Findings were driven by afternoon and evening caffeine consumption. Reduced sleep efficiency was associated with increased afternoon caffeine intake the following day (β = -.006; 95% CI = -.012, -.001; P = .01). Caffeine consumption, especially afternoon and evening use, impacts several aspects of adolescent sleep health. In contrast, most sleep indicators did not affect next-day caffeine use, suggesting multiple drivers of adolescent caffeine consumption. Federal mandates requiring caffeine content labeling and behavioral interventions focused on reducing caffeine intake may support adolescent sleep health. Lunsford-Avery JR, Kollins SH, Kansagra S, Wang KW, Engelhard MM. Impact of daily caffeine intake and timing on electroencephalogram-measured sleep in adolescents. J Clin Sleep Med. 2022;18(3):877-884.


The 474-Kilobase-Pair Complete Genome Sequence of CeV-01B, a Virus Infecting Haptolina (Chrysochromulina) ericina (Prymnesiophyceae).
We report the complete genome sequence of CeV-01B, a large double-stranded DNA virus infecting the unicellular marine phytoplankton Haptolina (formerly Chrysochromulina) ericina. CeV-01B and its closest relative Phaeocystis globosa virus define an emerging subclade of the Megaviridae family with smaller genomes and particles than the originally described giant Mimiviridae infecting Acanthamoeba.


Determination, by radioimmunoassay, of the mass of lactate dehydrogenase isoenzyme 1 in human serum and of its rate of removal from serum after a myocardial infarction.
In this radioimmunoassay of lactate dehydrogenase-1 (LD-1; EC 126.96.36.199) in human serum we use a commercial LD-1-selective assay system and a goat antiserum. We have determined the fractional rate of disappearance from serum and the half-life of LD-1, in terms of both enzyme activity and enzyme mass, in 21 myocardial infarction patients. Our evidence suggests that this isoenzyme is inactivated in serum. Furthermore, our data suggest that the conventionally accepted half-life of about 110 h for serum LD-1 activity may grossly overestimate the actual LD-1 half-life in many post-myocardial infarction patients.


Regulation by insulin and insulin-like growth factor of 2-deoxyglucose uptake in primary ependymal cell cultures.
Ependymal cells have been reported to express the facilitative glucose carriers GLUT1, GLUT2, and GLUT4, as well as glucokinase. They are therefore speculated to be part of the cerebral glucose sensing system and may also respond to insulin with alterations in their glucose uptake rate. A cell culture model was employed to study the functional status of ependymal insulin-regulated glucose uptake in vitro. Insulin increased the uptake of the model substrate 2-deoxyglucose (2-DG) dependent on the insulin concentration. This was due to a near doubling of the maximal 2-DG uptake rate. Insulin-like growth factor (IGF-1) was at least 10 times more potent than insulin in stimulating the rate of ependymal 2-DG uptake, suggesting that IGF-1, rather than insulin, is the physiological agonist regulating glucose transport in ependymal cells. The predominant glucose transporter in ependymal cell cultures was found to be GLUT1, which is apparently regulated by IGF-1 in ependymal cells.


Analogues of [(triethylsilyl)ethynyl]estradiol as potential antifertility agents.
Various 17 alpha-ethynylsteroids were prepared and derivatized as the corresponding triethylsilyl compounds 2-35, which were examined for a ratio of antifertility to estrogenic activity that would be more beneficial than that of the presently used agent. Among the triethylsilyl compounds evaluated, only 23 displayed this desired ratio, although two other compounds without the triethylsilyl moiety, 18 and 26, shared similar characteristics.


Impact of extraction and elution media on non-size effects in size exclusion chromatography of proteins.
Size exclusion chromatography is extensively used to separate proteins and to determine their apparent molecular weights. It separates proteins based on hydrodynamic volume, but interactions between the chromatography resin and proteins lead to non-size effects. This report discusses the impact of co-solvents [salt, urea, sodium dodecyl sulfate (SDS), dithiothreitol] in extraction media when separating wheat gluten proteins, soy glycinin, bovine serum albumin and ovalbumin on a Biosep-SEC-S4000 column. With acetonitrile/water (1:1, v/v) containing 0.05% (v/v) trifluoroacetic acid as eluent, salts and SDS in the extraction media increase while urea decreases non-size effects. Most gluten and globular proteins are extractable in sodium phosphate buffer (0.050M; pH 6.8) containing 2.0% (w/v) SDS. This chromatographic medium allows analyzing mixtures of various proteins without any non-size effects.


The surface to volume ratio of mitochondria, a suitable parameter for evaluating mitochondrial swelling. Correlations during the course of myocardial global ischaemia.
Cellular changes occurring in the left ventricular myocardium during ischaemia after different methods of cardiac arrest have been evaluated by morphological and morphometric parameters: volume densities of mitochondria (VVMi), sarcoplasm (VVSp), myofibrils (VVMf), surface densities of mitochondria (SVMi). The surface to volume ratio of mitochondria (SVratioMi) has been used as an independent parameter of mitochondrial swelling. Since ischaemic swelling of myocardial cells increases the volume of the reference space and ischaemic swelling of mitochondria decreases the free sarcoplasm, VVMi and VVSp cannot be considered as reliable indicators of the degree of oedema. SVMi/VVMf remains nearly constant after different forms of cardiac arrest, demonstrating the integrity of mitochondrial outer membranes. The inverse linear ratio between SVratioMi and the mean mitochondrial volume indicates that the increase in mitochondrial volume is achieved by surface smoothing. Loss of matrix structure and fragmentation of cristae occur at an SVratioMi of about 5.8, cristolysis at 5.5 to 5.6 and amorphous matrix densities at an SVratioMi of less than 5.5 micron2/micron3. The SVratioMi is a suitable parameter for evaluating mitochondrial swelling both at the onset and during global myocardial ischaemia, independent of the method of cardiac arrest used. It serves as an indicator of the state of structural preservation of mitochondria during ischaemia.


Qualitative Analysis of Barriers and Facilitators to Glaucoma Medication Adherence in a Randomized Controlled Trial Intervention.
In the Medication Adherence In Glaucoma To Improve Care trial, 200 veterans with medically-treated glaucoma were randomized to an intervention designed to improve glaucoma medication adherence or to usual care. In the 6 months after intervention, the mean proportion of doses taken on schedule was higher for participants in the intervention group compared with controls (0.85 vs. 0.62, P < 0.001). The purpose of this study was to use a mixed-methods approach to compare barriers and facilitators with adherence among participants through qualitative analysis of structured interviews. This is an analysis of interviews conducted from patients participating in a clinical trial. Participants from the intervention arm were separated into quartiles based on medication adherence according to the electronic monitor to sample from high and low responders to the intervention. We interviewed 23 participants; 11 participants with low adherence and 12 with high adherence. Interviews were conducted over telephone and transcribed. Staff members used grounded theory to conduct content analysis and code the transcribed interviews. The iterative process produced categories of common barriers and facilitators for medication adherence. The frequency of responses addressing common barriers and facilitators were compared between participants with high and low adherence. In the lowest- and highest-adherence groups, a difficult schedule was the most cited barrier for regular drop usage (63.6% and 58.3%, respectively). In the lowest and highest-adherence groups, the most cited facilitator for adherence was use of the smart bottle (100% and 91.7%, respectively). In the lowest-adherence group, 72.7% of participants cited that improved ability to administer drops was a benefit from the intervention. In the highest-adherence group, 75% of participants cited increased disease knowledge and formation of habits as facilitators from the intervention. Of the 22 of 23 participants who mentioned the smart bottle, 100% cited that they had increased adherence and would continue using the smart bottle. Using dosing reminders and personalized patient education may be important avenues for addressing difficulties with adhering to an eye drop schedule to improve glaucoma self-management. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Ultrasound-Assisted Neuronavigation-Guided Removal of a Live Worm in Cerebral Sparganosis.
Cerebral sparganosis is a rare zoonotic infestation that often mimics glioma and metastatic tumors. A 71-year-old man presented with disturbing dysarthria. Initial neuroimages were suggestive of glioma. However, the histology was suggestive of inflammatory lesion. Follow-up neuroimages and serology were suggestive of sparganosis. He subsequently had craniotomy with ultrasound-guided aspiration of a live worm. Saline-soaked Surgicel was used to provide an acoustic window. Ultrasonography was helpful in the intraoperative localization of the worm and is recommended when intraoperative magnetic resonance is not readily available.


Irreducible inguinal hernia in children below two years of age.
Eighty-five cases of irreducible inguinal hernia in children below 2 years of age were reviewed. Non-operative treatment was successful in 71 (84 per cent); 14 children required emergency surgery. The younger the child and the longer the duration of symptoms at presentation, the worse was the outcome of non-operative treatment. In 35 (41 per cent) children the diagnosis of inguinal hernia had been made before irreducibility. There is an increased incidence of postoperative complication associated with irreducibility, especially in preterm infants. Early diagnosis of inguinal hernia in young children and prompt referral for surgery is recommended.


Advances in Treatments in Muscular Dystrophies and Motor Neuron Disorders.
Increased understanding of disease pathophysiology and advances in gene therapies and drug technologies are revolutionizing treatment of muscular dystrophies and motor neuron disorders (MNDs). New drugs have been approved for Duchenne muscular dystrophy, spinal muscular atrophy, and amyotrophic lateral sclerosis. For other diseases, new targets have been identified, and new therapies are in clinical trials. The impact of such therapies will be fully understood only in the next decades. Cost burden and accessibility are major challenges in the wide application of new drugs. This article reviews advances in gene therapies, newly approved drugs, and therapeutic promises in muscular dystrophies and MNDs.


Identification of tear-based protein and non-protein biomarkers: Its application in diagnosis of human diseases using biosensors.
Discovery of robust, selective and specific biomarkers are important for early diagnosis and monitor progression of human diseases. Eye being a common target for several human diseases, vision impediment and complications are often associated with systemic and ocular diseases. Tears are bodily fluids that are closest to eye and are rich in protein content and other metabolites. As a biomarker repository, it advantages over other bodily fluids due to the ability to collect it non-invasively. In this review, we highlight some recent advancements in identification of tear-based protein biomarkers like lacryglobin and cystatin SA for cancer; interleukin-6 and immunoglobulin-A antibody for COVID-19; tau, amyloid-β-42 and lysozyme-C for Alzheimer's disease; peroxiredoxin-6 and α-synuclein for Parkinson's disease; kallikrein, angiotensin converting enzyme and lipocalin-1 for glaucoma; lactotransferrin and lipophilin-A for diabetic retinopathy and zinc-alpha-2 glycoprotein-1, prolactin and calcium binding protein-A4 for eye thyroid disease. We also discussed identification of tear based non-protein biomarkers like lysophospholipids and acetylcarnitine for glaucoma, 8-hydroxy-2'-deoxyquanosine and malondialdehyde for thyroid eye disease. We elucidate technological advancement in developing tear-based biosensors for diagnosis and monitoring diseases such as diabetes, diabetic retinopathy and Alzheimer's disease. Altogether, the study of tears as potential biomarkers for early diagnosis of human diseases is promising.


Waste plastics pyrolytic oil is a source of diesel fuel: A recent review on diesel engine performance, emissions, and combustion characteristics.
Most waste plastics can be converted into automobile fuel through the pyrolysis process. Plastic pyrolysis oil (PPO) has a heating value comparable with commercial diesel. The properties of PPOs depend on parameters such the plastic and pyrolysis reactor types, temperature, reaction time, heating rate, etc. This study reviews the performance, emissions, and combustion characteristic of diesel engines fuelled with neat PPO, PPO and diesel blends, and PPO with oxygenated additives. PPO has higher viscosity and density, higher sulphur content, lower flash point, lower cetane index and an unpleasant odour. PPO displays a higher delay in ignition during the premixed combustion phase. The literatures reported that diesel engines can run with PPO without any modification to the engine. This paper reveals that the brake specific fuel consumption can be lowered by 17.88 % by using neat PPO in the engine. Brake thermal efficiency can be reduced by 17.26 % while blends of PPO and diesel are used. Some studies say NOx emission can be reduced up to 63.02 %, however, others indicate that it can be increased up to 44.06 % compared to diesel when PPO is used in engines. The highest reduction in CO2 emission was found to be 47.47 % using blends of PPO and diesel; conversely, the highest increase was documented as 13.04 % when only PPO is used as fuel. In summary, PPO has very high potential as a substitute for commercial diesel fuel through further research and by improving its properties through post-treatment processing such as distillation and hydrotreatment.


Evaluation of cardiac masses by real-time perfusion imaging echocardiography.
Diagnosis of cardiac masses is still challenging by echocardiography and distinguishing tumors from thrombi has important therapeutical implications. We sought to determine the diagnostic value of real-time perfusion echocardiography (RTPE) for cardiac masses characterization. We prospectively studied 86 patients, 23 with malignant tumors (MT), 26 with benign tumors (BT), 33 with thrombi and 6 with pseudotumors who underwent RTPE. Mass perfusion was analyzed qualitatively and blood flow volume (A), blood flow velocity (β), and microvascular blood flow (A x β) were determined by quantitative RTPE. Logistic regression models showed that the probability of having a tumor increased by 15.8 times with a peripheral qualitative perfusion pattern, and 34.5 times with a central perfusion pattern, in comparison with the absence of perfusion. Using quantitative RTPE analysis, thrombi group had parameters of blood flow lower than tumor group. A values for thrombi, MT, and BT were 0.1 dB (0.01-0.22), 2.78 dB (1-7) and 2.58 dB (1.44-5), respectively; p < 0.05, while A x β values were 0.0 dB/s(-1) (0.01-0.14), 2.00 dB/s(-1) (1-6), and 1.18 dB/s(-1) (0.52-3), respectively; p < 0.05. At peak dipyridamole stress, MT had greater microvascular blood volume than BT [A = 4.18 dB (2.14-7.93) versus A = 2.04 dB (1.09-3.55); p < 0.05], but no difference in blood flow [Axβ = 2.46 dB/s(-1) (1.42-4.59) versus Axβ = 1.55 dB/s [1] (0.51-4.08); p = NS]. An A value >3.28 dB at peak dipyridamole stress predicted MT (AUC = 0.75) and conferred 5.8-times higher chance of being MT rather than BT. RTPE demonstrated that cardiac tumors have greater microvascular blood volume and regional blood flow when compared with thrombi. Dipyridamole stress was useful in differentiating MT from BT.


Characterization of ligand-binding properties of the human BMP type II receptor extracellular domain.
ActR-IIA, ActR-IIB, and BMPR-II are low-affinity type II receptors that bind bone morphogenetic proteins (BMPs) in the same overall manner. The binding of BMPs by ActR-IIs has been analyzed structurally and functionally, but no detailed analysis of BMPR-II has been reported. The objective of this study was to determine ligand-binding epitopes and specificity determinants in two regions, the hydrophobic patch and the A-loop of the BMPR-II extracellular domain (ECD). A series of alanine-substituted variants was generated using a recently published X-ray structure of the unliganded form of the ovine BMPR-II ECD as a guide. These variants were characterized using one-dimensional NMR and functional activity assays with BMP-2, BMP-7 and GDF-5 as ligands. The results showed that alanine substitutions of conserved residues W85 and Y113 within the hydrophobic patch of the ECD differentially perturbed BMP ligand binding without disrupting receptor folding, suggesting that they are critical determinants for ligand binding and ligand specificity. Our results further revealed that the nonconserved residue L69 in the hydrophobic patch contributes to ligand-binding activity and specificity. Mutations of several residues within the A-loop resulted in minimal effects on the binding of the different BMP ligands. Overall, these observations identify several amino acid residues that play different roles in BMPR-II and ActR-II and thereby enable BMPR-II and ActR-IIs to bind different subclasses of BMP ligands.


New tricyclic systems as photosensitizers towards triple negative breast cancer cells.
Nineteen pyrrolo[1,2-h][1,7]naphthyridinones and pyrido[2,3-c]pyrrolo[1,2-a]azepinones were synthesized as new tricyclic systems in which the pyridine ring is annelated to the 6,7-dihydroindolizin-8(5H)-one and 5,6,7,8-tetrahydro-9H-pyrrole[1,2-a]azepine-9-one moieties to obtain potential photosensitizing agents. They were tested for their photoantiproliferative activity on a triple-negative breast cancer cell line, MDA-MB-231, in the dark and under UVA light (2.0 J/cm2). We demonstrated that their toxicity, only when exposed to light, was primarily due to the generation of reactive oxygen species while their photodegradation products were not responsible for their activity. The most active compounds exhibited photocytotoxicity with IC50 values at low micromolar level inducing a decrease in the intracellular content of thiol, thus triggering cancer cell death through apoptosis. All the pyridone derivatives revealed to be pure photosensitizers with preferential photocytotoxic activity towards cancerous over healthy cells. Altogether, the results obtained confirm pyrrolo[1,2-h][1,7]naphthyridinones and pyrido[2,3-c]pyrrolo[1,2-a]azepinones as promising photosensitisers against triple-negative breast cancer.