Influence of ultrasound assisted metal-free Fenton reaction on the structural characteristic and immunostimulatory activity of a β-D-glucan isolated from Dictyophora indusiata.
The present study aimed to evaluate the influence of ultrasound assisted H2O2/ascorbic acid reaction on the structural characteristic and immunostimulatory activity of a β-D-glucan isolated from D. indusiata, so as to reveal its potential structure-immunostimulatory activity relationship. A purified β-D-glucan, named as DP, was quickly isolated from D. indusiata, and further identified as a 1,3-β-D-glucan with 1,6-β-D-Glcp as branched chains, which exhibited a rigid rod chain conformation in 0.9 % (w/v) of NaCl solution. Furthermore, results showed that the primary structure of DP was overall stable after the degradation by ultrasound assisted H2O2/ascorbic acid reaction. However, the molar mass and chain conformation of DP obviously changed. In addition, DP and its degraded products exerted remarkable immunostimulatory activity in vitro and in vivo, which could activate the nuclear factor-κB (NF-κB) signaling pathway through toll-like receptor 4 (TLR4). Indeed, the immunostimulatory activity of DP was closely-correlated to its molar mass and chain conformation. An appropriate degradation of molar mass could promote its immunostimulatory activity. While the transformation of chain conformation from rigid rod to random coil could cause the significant decrease of its immunostimulatory activity. These findings are beneficial to better understanding the structure-immunostimulatory activity relationship of β-D-glucans from edible mushrooms.


Therapeutic efficacy of platelet transfusion treated with amotosalen/UVA pathogen inactivation technology (INTERCEPTTM Blood System) in acute myeloid leukemia patients undergoing chemotherapy with curative intent: a single center experience.
The INTERCEPTTM Blood System (Intercept Blood System, Cerus Europe BV, Amersfoort, the Netherlands) has been used to reduce or inactivate pathogen load in platelet concentrates in France for three years. After comparing the transfusion efficiency between pathogen-reduced platelets (PR_PLT) and untreated platelet products (U_PLT), our single-center observational study assessed the effectiveness of PR_PLT for the prevention of bleeding and for therapeutic treatment of WHO grade 2 bleeding in 176 patients undergoing chemotherapy with curative intent for acute myeloid leukemia (AML). The main endpoints were the 24-hour (h) corrected count increment (24h_CCI) after each transfusion, and time to next transfusion. Whereas the transfused doses tended to be higher in the PR_PLT group compared to U_PLT, there was a significant difference in intertransfusion interval (ITI) and 24h_CCI. In prophylactic transfusions, PR_PLT transfusions of >0.65×1011/10 kg, regardless of the age of the product (day 2 to day 5), resulted in a 24h_CCI similar to that of the untreated platelet product; this meant the patient could be transfused at least every 48h. In contrast, most PR_PLT transfusions of <0.55×1011/10 kg did not achieve a transfusion interval of 48h. In the context of WHO grade 2 bleeding, PR_PLT transfusions >0.65×1011/10 kg and storage of less than 4 days seems more effective in stopping bleeding. These results, which must be confirmed by prospective studies, indicate the need for vigilance regarding the quantity and quality of PR_PLT products used to treat patients at risk of bleeding crisis. Future prospective studies are needed to confirm these findings.


Differential inhibition of fungal oxidosqualene cyclase by 6E and 6Z isomers of 2,3-epoxy-10-aza-10,11-dihydrosqualene.
Inhibitory properties of 6E (compound 1) and 6Z (compound 2) isomers of 2,3-epoxy-10-aza-10,11-dihydrosqualene against oxidosqualene-lanosterol cyclase were assayed on microsomes and whole cells of Saccharomyces cerevisiae and Candida albicans. Only the 6E isomer (compound 1), bearing a correct substrate-like configuration, strongly inhibited the enzyme both in microsomes and cell cultures. The difference between compounds 1 and 2 (which had an unfavorable geometry) was especially evident when measuring [14C]acetate incorporation into non-saponifiable lipids extracted from treated cells. While isomer Z was totally ineffective at up to 30 microM, in cells treated with 5 microM isomer E, labelled oxidosqualene, the level of which was negligible in the control, rose to over 60% of the non-saponifiable lipids.


Pediatric Nail Disorders.
Many pediatric nail findings are normal variants and are no cause for alarm. Others represent congenital abnormalities or genetic syndromes for which there is no cure. Still others are inflammatory or infectious entities that require treatment. Pediatric nail disorders are reviewed, along with management.


Experimental exposure of zebrafish, Danio rerio (Hamilton), to Mycobacterium marinum and Mycobacterium peregrinum reveals the gastrointestinal tract as the primary route of infection: a potential model for environmental mycobacterial infection.
The natural route by which fish become infected with mycobacteria is unknown. Danio rerio (Hamilton) were exposed by bath immersion and intubation to Mycobacterium marinum and Mycobacterium peregrinum isolates obtained from diseased zebrafish. Exposed fish were collected over the course of 8 weeks and examined for the presence of mycobacteriosis. Mycobacteria were consistently cultured from the intestines, and often from the livers and spleens of fish exposed by both methods. Mycobacteria were not observed in the gills. Histological analysis revealed that fish infected with M. marinum often developed granulomas accompanied by clinical signs of mycobacteriosis, while infection with M. peregrinum infrequently led to clinical signs of disease. Passage of the bacteria through environmental amoebae (Acanthamoeba castellani) was associated with increased growth of M. peregrinum over the course of 8 weeks, when compared to infection with the bacteria not passed through amoebae. The results provide evidence that zebrafish acquire mycobacteria primarily through the intestinal tract, resulting in mycobacterial dissemination.


Preoperative high-resolution magnetic resonance imaging can identify good prognosis stage I, II, and III rectal cancer best managed by surgery alone: a prospective, multicenter, European study.
To assess local recurrence, disease-free survival, and overall survival in magnetic resonance imaging (MRI)-predicted good prognosis tumors treated by surgery alone. The MERCURY study reported that high-resolution MRI can accurately stage rectal cancer. The routine policy in most centers involved in the MERCURY study was primary surgery alone in MRI-predicted stage II or less and in MRI "good prognosis" stage III with selective avoidance of neoadjuvant therapy. Data were collected prospectively on all patients included in the MERCURY study who were staged as MRI-defined "good" prognosis tumors. "Good" prognosis included MRI-predicted safe circumferential resection margins, with MRI-predicted T2/T3a/T3b (less than 5 mm spread from muscularis propria), regardless of MRI N stage. None received preoperative or postoperative radiotherapy. Overall survival, disease-free survival, and local recurrence were calculated. Of 374 patients followed up in the MERCURY study, 122 (33%) were defined as "good prognosis" stage III or less on MRI. Overall and disease-free survival for all patients with MRI "good prognosis" stage I, II and III disease at 5 years was 68% and 85%, respectively. The local recurrence rate for this series of patients predicted to have a good prognosis tumor on MRI was 3%. The preoperative identification of good prognosis tumors using MRI will allow stratification of patients and better targeting of preoperative therapy. This study confirms the ability of MRI to select patients who are likely to have a good outcome with primary surgery alone.


Quantitative analysis of regional airways obstruction using dynamic hyperpolarized 3He MRI-preliminary results in children with cystic fibrosis.
To investigate regional airways obstruction in patients with cystic fibrosis (CF) with quantitative analysis of dynamic hyperpolarized (HP) (3)He MRI. Dynamic radial projection MRI of HP (3)He gas was used to study respiratory dynamics in a group of eight children with CF. Signal kinetics in a total of seven regions of interest (ROIs; three in each lung, and one in the trachea) were compared with the results of spirometric pulmonary function tests (PFTs). The tracheal signal intensity was used as a form of "input function" to normalize for input flow effects. A pattern of low flow rate in the upper lobes was observed. When the flow measurements from the peripheral ROIs were averaged to obtain an index of flow in the peripheral lung, a good correlation was found (P = 3.74 x 10(-5)) with the forced expired volume in one second (FEV1). These results suggest that a quantitative measurement of localized airways obstruction in the early stages of CF may be obtained from dynamic (3)He MRI by using the slope of the signal rise as a measure of air flow into the peripheral lung. This study also demonstrates that children can cooperate well with the (3)He MRI technique.


Areal and laminar distribution of some pulvinar cortical efferents in rhesus monkey.
The areal and laminar distribution of the cortical efferents of the medial, lateral and inferior pulvinar nuclei (PM, PL and PI respectively) were determined in rhesus monkey using autoradiography and Horseradish Peroxidase (HRP). The autoradiographic data indicated that: areas 8a, 45 and 46 on the convexity and 11 and 12 on the orbital surface of the frontal lobe received projections from PM; areas 20, 21 and 22 in temporal lobe received projections from PM primarily with caudal-medial parts of PM projecting to more rostral-dorsal parts of temporal lobe and rostral-lateral parts of PM projecting to more caudal-ventral parts of temporal lobe but PL also sends some efferents to caudal temporal lobe; areas 5 and 7 in parietal lobe and 18 and 19 in occipital lobe received projections primarily from the region in pulvinar comprising PL and PI with the more ventral parts of this region porsal parts of this region projecting to the more dorsal-lateral and medial parts of parieto-occipital cortex and with PM comtributing slightly to these projections rostrally. The autoradiographic information on the pulvinar projections to frontal lobe and temporal pole was supplemented by data derived from cortical HRP injections. These indicated that although only PM of the pulvinar subnuclei projected to these regions, three other caudal thalamic structures, i.e., medial dorsal nucleus, nucleus limitans and suprageniculate nucleus also projected to these regions raising some questions about the identity of the densocellular part of the medial dorsal nucleus which has also been considered to be part of pulvinar. The laminar distribution of pulvinar cortical efferents was uniformly similar regardless of the pulvinar recipient area examined. Elevated numbers of silver grains were observed over all cortical layers, but the silver grains were densest over the deep parts of layer III. The thalamic reticular nucleus was the only diencephalic structure observed to receive projections from pulvinar and it did so from PM, PL and PI. The pulvinar's efferents are to homotypical rather than heterotypical cortex and its connections are most extensive with cortex rather than with subcortical structures.


Stereotactic radiotherapy of brain metastases: clinical impact of three-dimensional SPACE imaging for 3T-MRI-based treatment planning.
For planning CyberKnife stereotactic radiosurgery (CK SRS) of brain metastases (BM), it is essential to precisely determine the exact number and location of BM in MRI. Recent MR studies suggest the superiority of contrast-enhanced 3D fast spin echo SPACE (sampling perfection with application-optimized contrast by using different flip angle evolutions) images over 3D gradient echo (GE) T1-weighted MPRAGE (magnetization-prepared rapid gradient echo) images for detecting small BM. The aim of this study is to test the usability of the SPACE sequence for MRI-based radiation treatment planning and its impact on changing treatment. For MRI-based radiation treatment planning using 3T MRI in 199 patients with cerebral oligometastases, we compared the detectability of BM in post-gadolinium SPACE images, post-gadolinium MPRAGE images, and post-gadolinium late-phase MPRAGE images. When SPACE images were used for MRI-based radiation treatment planning, 29.8% and 16.9% more BM, respectively, were detected and included in treatment planning than in the post-gadolinium MPRAGE images and the post-gadolinium late-phase MPRAGE images (post-gadolinium MPRAGE imaging: ntotal = 681, mean ± SD 3.4 ± 4.2; post-gadolinium SPACE imaging: ntotal = 884, mean ± SD 4.4 ± 6.0; post-gadolinium late-phase MPRAGE imaging: ntotal = 796, mean ± SD 4.0 ± 5.3; Ppost-gadolinium SPACE imaging versus post-gadolinium MPRAGE imaging < 0.0001, Ppost-gadolinium SPACE imaging versus post-gadolinium late-phase MPRAGE imaging< 0.0001). For 3T MRI-based treatment planning of stereotactic radiosurgery of BM, we recommend the use of post-gadolinium SPACE imaging rather than post-gadolinium MPRAGE imaging.


Family patterns in four dimensions of lateral preference.
Hand, eye, foot, and ear preference were examined in a sample of 459 biologically related parent-offspring triads and 434 sibling pairs. Intercorrelations were computed using the side of preference as the dependent variables and then again using the absolute strength of the displayed preference irrespective of side. The directional analyses did not show strong patterns of familial similarities; however, relatives did tend to resemble each other in the degree of lateralization manifested. Maternal and paternal resemblance to offspring vary over the four indices of laterality, and there are some suggestions of sex-specific interactions. These results imply that genetic influence may operate to affect the degree of expressed preference, while the side of preference may not be genetically encoded. These findings also suggest that lateral preferences for limb and sense organ may not be due to a single causal mechanism.


Improving Support for Care at Home: Parental Needs and Preferences When Caring for Children with Medical Complexity.
We sought to characterize the current supports used by parents to care for children with medical complexity (CMC) at home and parental preferences for additional supports to meet identified gaps. Semistructured interviews were conducted with parents of 18 CMC. Interviews were transcribed then analyzed using a constant comparative approach. Extended family and community offloaded nonmedical tasks, assisted financially, gave emotional reinforcement, and cared for CMC. Home health providers also directly cared for CMC, but access and quality varied. Government programs paid for in-home care, but eligibility varied. Parents wanted more paid home care but also more support completing nonmedical tasks, mitigating financial strains, and accessing mental health services. Parents of CMC relied on family and community members to help fill existing gaps in-home care, but gaps remained, suggesting the need for more medical and social supports for the in-home care of CMC and their families.


Gonadotroph adenoma causing ovarian hyperstimulation syndrome in a premenopausal woman.
Gonadotroph adenomas occur commonly in middle-aged adults without any specific endocrinological symptoms. To date, only 30 cases of gonadotropinoma causing ovarian hyperstimulation syndrome in pre-menopausal women have been reported. A 37-year old woman with pituitary macroadenoma and hyperprolactinaemia was admitted to the Department of Endocrinology, Diabetology and Isotope Therapy. She presented with recurrent ovarian cysts, menstrual disturbances, headaches, visual impairment and galactorrhea. Her endocrine profile showed normal values of FSH, elevated concentrations of estradiol and suppressed LH levels. Transsphenoidal resection of the tumor tissue resulted in normalization of the hormone values and improvement in the clinical picture. Gonadotroph adenomas should be considered in the differential diagnosis in premenopausal women with OHSS.


Multidisciplinary team meetings in prosthetic joint infection management: A qualitative study.
Prosthetic joint infections (PJIs) cause substantial morbidity to patients and are extremely challenging for clinicians. Their management can include multiple operations, antibiotics, and prolonged hospital admissions. Multidisciplinary team meetings (MDTM) are increasingly used for collaborative decision-making around the management of PJIs, but thus far there has been no examination of the role of MDTM in decisions and management. This study aimed to examine interactions in a PJI MDTM to identify the dynamics in decision-making, and inter-specialty relationships more broadly. Twelve MDTMs over 7 months at an Australian tertiary referral hospital were video recorded, transcribed, and thematic analysis was performed. Thematic analysis revealed four key areas of collaborative discussion 1. Achieving Inter-specialty Balance: The role of the multidisciplinary team discussion in providing balance between specialty views, and traversing the barriers between specialty interactions. 2. Negotiating Grey zones: there was frequent discussion of the limits of tests, interpretation of symptoms, and the limits of proposed operative strategies, and the resultant tensions of balancing ideal care vs pragmatic decision-making, and divergent goals of care. 3. Tailoring Treatment: identification of individual patient factors (both physiological and behavioural) and risks into collaborative decision-making. 4. Affording Failure: creating affordances in communication to openly discuss 'failure' to eliminate infection and likely negative outcomes. MDTM in the management of prosthetic joint infections serve multiple functions including: achieving interdisciplinary balance; effective grey zone management, tailoring reconfigured care; and most critically, recognition of 'failure' to eliminate infection, a communicative affordance most likely leading to better care.


The information needs of North American parents of children with asthma: a state-of-the-science review of the literature.
Asthma, the most common chronic disease of childhood, presents diverse challenges to parents who are responsible for its management. Parents must be informed regarding symptom recognition, medications, prevention, and treatment to effectively minimize acute exacerbations and asthma sequela. Current approaches to asthma education do not address the vast range of information needs of parents, and few studies explicitly identify parental information needs in a comprehensive manner. To address this gap and to create a parental information needs taxonomy, a "state-of-the-science" review of the literature was conducted. Three electronic databases were searched and articles were screened according to pre-established inclusion criteria. Of 164 articles retrieved, 11 articles met the inclusion criteria and were included in the review. Parental information needs can be classified in the following categories: asthma basics, treatment modalities, coping, and medical expectations. This information needs taxonomy may help practitioners better address the information needs of parents of children with asthma.


Cellular mechanisms of chlorothiazide and cellular potassium depletion on Mg2+ uptake in mouse distal convoluted tubule cells.
The use of the distally-acting diuretic, chlorothiazide, has been reported to have important effects on renal magnesium handling. The cellular mechanisms of chlorothiazide action on Mg2+ uptake was investigated in immortalized mouse distal convoluted tubule (MDCT) cells. Intracellular free Mg2+ concentration was determined by microfluorescence. Mg2+ transport was measured as a function of change in intracellular Mg2+ concentration with time following placement of Mg2+-depleted cells into a buffer containing 1.5 mM magnesium. The uptake rate of Mg2+ into Mg2+-depleted cells was 179 +/- 28 nM/second. Mg2+ uptake was dependent on the membrane voltage as membrane hyperpolarization enhanced uptake whereas depolarization diminished transport. Chlorothiazide increased Mg2+ uptake by 58%, from 179 +/- 28 to 283 +/- 23 nM/second. The ability of chlorothiazide to stimulate Mg2+ uptake in MDCT cells was concentration-dependent and related to the diuretic-induced hyperpolarization of the plasma membrane. These studies support the notion that acute chlorothiazide administration enhances renal magnesium conservation through its effects on Mg2+ transport within the distal convoluted tubule. Since chronic chlorothiazide administration may result in hypokalemia as well as hypomagnesemia, Mg2+ uptake was determined in potassium-depleted MDCT cells. Mg2+ uptake was diminished, 80 +/- 24 nM/second, in potassium depleted cells. Hyperpolarization of the plasma membrane with the cell permanent anion, SCN-, corrected Mg2+ uptake in potassium depleted cells suggesting that the basis for diminished uptake may, in part, be due to depolarization of the membrane voltage. In summary, acute chlorothiazide stimulates Mg2+ transport in MDCT cells. We postulate that chronic chlorothiazide use may lead to hypokalemia that in turn diminishes Mg2+ transport in the distal tubule resulting in urinary magnesium-wasting.


SUMOylation controls the binding of hexokinase 2 to mitochondria and protects against prostate cancer tumorigenesis.
Human hexokinase 2 is an essential regulator of glycolysis that couples metabolic and proliferative activities in cancer cells. The binding of hexokinase 2 to the outer membrane of mitochondria is critical for its oncogenic activity. However, the regulation of hexokinase 2 binding to mitochondria remains unclear. Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K492. SUMO-specific protease SENP1 mediates the de-SUMOylation of hexokinase 2. SUMO-defective hexokinase 2 preferably binds to mitochondria and enhances both glucose consumption and lactate production and decreases mitochondrial respiration in parallel. This metabolic reprogramming supports prostate cancer cell proliferation and protects cells from chemotherapy-induced cell apoptosis. Moreover, we demonstrate an inverse relationship between SENP1-hexokinase 2 axis and chemotherapy response in prostate cancer samples. Our data provide evidence for a previously uncovered posttranslational modification of hexokinase 2 in cancer cells, suggesting a potentially actionable strategy for preventing chemotherapy resistance in prostate cancer.


Analysis of the visual cycle in cellular retinol-binding protein type I (CRBPI) knockout mice.
To determine whether the visual cycle is affected in mice without a functional gene for cellular retinol-binding protein type I (CRBPI(-/-) mice). Visual-cycle retinoids and rhodopsin levels were analyzed in eyes of dark adapted (DA) CRBPI(-/-) and wild-type (wt) mice before and during recovery from a flash. The rate of dark adaptation was analyzed using electroretinography (ERG). all-trans-retinyl esters were reduced to approximately 33% of wt levels in DA CRBPI(-/-) mice. Recovery from a flash in wt mice produced transient accumulations of all-trans-retinal and all-trans-retinyl ester, as the pulse of retinoid produced by the flash traversed the visual cycle. In CRBPI(-/-) mice, all-trans-retinal accumulated transiently, as in wt mice. However, all-trans-retinol also accumulated transiently in the neural retina, and the transient increase in all-trans-retinyl ester of the wt was reduced. Rates of 11-cis-retinal and rhodopsin formation were comparable in wt and CRBPI(-/-) mice. Dark adaptation was delayed by a factor of approximately two. The accumulation of all-trans-retinol in neural retina, in the absence of CRBPI and the reduced amount of retinyl esters in the RPE suggest that the binding protein participates in a process that drives diffusion of all-trans-retinol from photoreceptor cells to RPE, perhaps by delivering vitamin A to lecithin-retinol acyltransferase (LRAT) for esterification. Because the perturbation occurred upstream of a slow step of the visual cycle, there was no major impairment of the rate of visual pigment regeneration.


[Isolated fracture of humeral eminence in children].
Fracture of the humeral bone block can be recognized by a lateral rentgenogram. An abnormal ratio of bones in the joint is seen as an overlaping of the elbow bone metaphysis shadow upon the shadow of the capitate eminence of the humeral bone in the shape of a crescent.


Epigenomic machinery regulating pediatric AML: Clonal expansion mechanisms, therapies, and future perspectives.
Acute myeloid leukemia (AML) is a heterogeneous disease with a genetic, epigenetic, and transcriptional etiology mainly presenting somatic and germline abnormalities. AML incidence rises with age but can also occur during childhood. Pediatric AML (pAML) accounts for 15-20% of all pediatric leukemias and differs considerably from adult AML. Next-generation sequencing technologies have enabled the research community to "paint" the genomic and epigenomic landscape in order to identify pathology-associated mutations and other prognostic biomarkers in pAML. Although current treatments have improved the prognosis for pAML, chemoresistance, recurrence, and refractory disease remain major challenges. In particular, pAML relapse is commonly caused by leukemia stem cells that resist therapy. Marked patient-to-patient heterogeneity is likely the primary reason why the same treatment is successful for some patients but, at best, only partially effective for others. Accumulating evidence indicates that patient-specific clonal composition impinges significantly on cellular processes, such as gene regulation and metabolism. Although our understanding of metabolism in pAML is still in its infancy, greater insights into these processes and their (epigenetic) modulation may pave the way toward novel treatment options. In this review, we summarize current knowledge on the function of genetic and epigenetic (mis)regulation in pAML, including metabolic features observed in the disease. Specifically, we describe how (epi)genetic machinery can affect chromatin status during hematopoiesis, leading to an altered metabolic profile, and focus on the potential value of targeting epigenetic abnormalities in precision and combination therapy for pAML. We also discuss the possibility of using alternative epidrug-based therapeutic approaches that are already in clinical practice, either alone as adjuvant treatments and/or in combination with other drugs.


Inguinal hernia repair in early infancy.
Controversy regarding the management of inguinal hernias in young infants stimulated this study. It was our hypothesis that inguinal hernia in young infants can and should be repaired at the time of presentation. In order to address this issue, the following questions were examined: How frequently are these hernias incarcerated and how should this be managed? What is the best timing of repair? Should the asymptomatic contralateral groin be explored? How do the recurrence and complication rates compare with those in older children? Have advances in anesthesia affected the treatment of these infants? The records of 384 infants less than 2 months of age who underwent inguinal herniorrhaphy from January 1985 to January 1990 at Children's Hospital and Medical Center in Seattle were reviewed. Nearly one fourth (24%) of the patients had incarcerated hernias. Preoperative reduction was successful 96% of the time. The hernia was then repaired within 48 hours. Six patients required urgent operation, but bowel resection was not necessary in any. Contralateral groin exploration was performed 96% of the time and was positive in 85%. The recurrence rate was 1.0%. Complications occurred in 2.3% of patients. There were no hernia-related deaths. Spinal anesthesia was used in 63 patients with no postoperative apnea. An aggressive approach toward prompt repair of hernias in this age group can result in a very low incidence of hernia-related complications. Repair can be carried out safely in the first 2 months of life with recurrence and complication rates comparable with those in older children. Spinal anesthesia may lower the rate of postoperative apnea.


Health plan-based mailed fecal testing for colorectal cancer screening among dual-eligible Medicaid/Medicare enrollees: Outcomes of 2 program models.
Health insurance plans are increasingly offering mailed fecal immunochemical test (FIT) programs for colorectal cancer (CRC) screening, but few studies have compared the outcomes of different program models (eg, invitation strategies). This study compares the outcomes of 2 health plan-based mailed FIT program models. In the first program (2016), FIT kits were mailed to all eligible enrollees; in the second program (2018), FIT kits were mailed only to enrollees who opted in after an outreach phone call. Participants in this observational study included dual-eligible Medicaid/Medicare enrollees who were aged 50 to 75 years and were due for CRC screening (1799 in 2016 and 1906 in 2018). Six-month FIT completion rates, implementation outcomes (eg, mailed FITs sent and reminders attempted), and program-related health plan costs for each program are described. All 1799 individuals in 2016 were sent an introductory letter and a FIT kit. In 2018, all 1906 were sent an introductory letter, and 1905 received at least 1 opt-in call attempt, with 410 (21.5%) sent a FIT. The FIT completion rate was 16.2% (292 of 1799 [95% CI, 14.5%-17.9%]) in 2016 and 14.6% (278 of 1906 [95% CI, 13.0%-16.2%]) in 2018 (P = .36). The overall implementation costs were higher in 2016 ($40,156) than 2018 ($34,899), with the cost per completed FIT slightly higher in 2016 ($138) than 2018 ($126). An opt-in mailed FIT program achieved FIT completion rates similar to those of a program mailing to all dual-eligible Medicaid/Medicare enrollees. Health insurance plans can use different program models to successfully mail fecal test kits for colorectal cancer screening to dual-eligible Medicaid/Medicare enrollees, with nearly 1 in 6 enrollees completing fecal testing.


Immune checkpoint inhibitors combined with chemotherapy/bevacizumab therapy for patients with advanced lung cancer and heavily treated with EGFR mutation: a retrospective analysis.
EGFR-mutated lung cancer poorly responded to anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy. Whether patients with EGFR-mutated lung cancer can benefit from anti-PD-1/PD-L1 therapy combined with other drugs remains controversial. We retrospectively evaluated the safety and efficacy of the PD-1 inhibitor combined with other drugs (chemotherapy and/or bevacizumab) in patients with EGFR-mutated lung cancer, who have progressed on EGFR-TKI treatment to determine the activity of the anti-PD-1/PD-L1 therapy combined with chemotherapy or/and bevacizumab therapy in heavily treated patients with EGFR-mutated lung cancer. We identified 56 patients with EGFR-mutated lung cancer treated with PD-1/PD-L1 inhibitors alone or combined with the chemotherapy/bevacizumab therapy. The objective response rates were assessed using RECIST v1.1. Adverse events (AEs) were graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Academic Ethics Committee of Jiangsu Cancer Hospital. (NO. 2019 160), and individual consent for this retrospective analysis was waived. Objective responses were observed in 6 of 56 (10.7%) patients, and the disease control rate was 53.6% (30/56). The median progression-free survival (PFS) was 3.33 months with 95% CI of 1.58-5.08 months. No patient achieved a complete response. All six patients that achieved PR were treated with the PD-1 inhibitor combined with chemotherapy or bevacizumab therapy. Three of the six patients who achieved PR were treated with radiotherapy combined with PD-1 inhibitor-based therapy. Patients treated with the PD-1 inhibitor-based therapy as second-line therapy showed relatively longer PFS and higher objective response rates than those treated with PD-1 inhibitor-based therapy as third- or late-line therapy (PFS: 5.50 vs. 3.27 months, P=0.301; objective response rates: 25.0% vs. 6.82%, P=0.071). No additional AE profile was observed. The PD-1 inhibitor combined with the chemotherapy/bevacizumab therapy showed acceptable toxicity profile and moderate efficacy on heavily treated advanced EGFR-mutated lung cancer after the exhaustion of target therapy.


Deep learning-enabled analysis of medical images identifies cardiac sphericity as an early marker of cardiomyopathy and related outcomes.
Quantification of chamber size and systolic function is a fundamental component of cardiac imaging. However, the human heart is a complex structure with significant uncharacterized phenotypic variation beyond traditional metrics of size and function. Examining variation in cardiac shape can add to our ability to understand cardiovascular risk and pathophysiology. We measured the left ventricle (LV) sphericity index (short axis length/long axis length) using deep learning-enabled image segmentation of cardiac magnetic resonance imaging data from the UK Biobank. Subjects with abnormal LV size or systolic function were excluded. The relationship between LV sphericity and cardiomyopathy was assessed using Cox analyses, genome-wide association studies, and two-sample Mendelian randomization. In a cohort of 38,897 subjects, we show that a one standard deviation increase in sphericity index is associated with a 47% increased incidence of cardiomyopathy (hazard ratio [HR]: 1.47, 95% confidence interval [CI]: 1.10-1.98, p = 0.01) and a 20% increased incidence of atrial fibrillation (HR: 1.20, 95% CI: 1.11-1.28, p < 0.001), independent of clinical factors and traditional magnetic resonance imaging (MRI) measurements. We identify four loci associated with sphericity at genome-wide significance, and Mendelian randomization supports non-ischemic cardiomyopathy as causal for LV sphericity. Variation in LV sphericity in otherwise normal hearts predicts risk for cardiomyopathy and related outcomes and is caused by non-ischemic cardiomyopathy. This study was supported by grants K99-HL157421 (D.O.) and KL2TR003143 (S.L.C.) from the National Institutes of Health.


Anterolateral thigh versus radial forearm flap for cervical esophageal reconstruction in cancer patients: A retrospective cohort study in Colombia.
Este estudio tuvo como objetivo describir los resultados clínicos del colgajo anterolateral de muslo y radial de antebrazo, para la reconstrucción hipofaríngea y esofágica en un hospital de cuarto nivel en Bogotá, Colombia. Estudio retrospectivo inlcuyo 38 pacientes a los que se les realizó reconstrucción funcional esofágica con colgajo de antebrazo radial o anterolateral de muslo (ALT) entre febrero de 2010 y diciembre de 2017. Edad media fue de 51 años. El 80% genero femeninp. Los defectos laringoesofágicos estuvieron presentes en el 80%. Se requirió reconstrucción circunferencial total en el 60% de los pacientes. Se realizaron injertos braquio-radiales en el 26% y colgajos anterolaterales de muslo en el 74%. La tasa global de complicaciones tempranas fue del 30%, de las cuales el 20% fueron fístulas (braquio-radial, 2,8%; colgajo libre de ALT, 8,3%). Las complicaciones tardías (20%) incluyeron estenosis y obstrucción de la luz del injerto distal. Solo el 10% de los pacientes no pudieron tolerar la alimentación oral y el 50% de este paciente necesitó gastrostomía permanente. En cuanto al seguimiento oncológico durante el postoperatorio de 24 meses, no se observó recidiva tumoral. Los resultados funcionales de la reconstrucción con colgajo braquio-radial y ALT fueron satisfactorios. Nuestros hallazgos sugieren que la ALT tiene una menor incidencia de complicaciones posoperatorias que el colgajo radial de antebrazo. La elección del tipo de colgajo dependerá del tamaño y la ubicación del defecto. Los defectos pequeños y parcialmente cubiertos se benefician del uso de un colgajo radial, y para reconstrucciones faríngeas más grandes y circunferenciales con posibles requisitos de radioterapia, se benefician de un colgajo ALT. This study aimed to describe clinical outcomes of anterolateral thigh (ALT) and radial forearm flap in hypopharyngeal and esophageal reconstruction in a fourth level hospital in Bogotá, Colombia. This retrospective study included 38 patients who esophageal functional reconstruction using radial forearm or ALT flap at our center between February 2010 and December 2017. Mean age was 51 years. About 80% of the included patients were females. Laryngoesophageal defects were present in 80%. Total circumferential reconstruction was required in 60% of patients. Brachial-radial grafts were performed in 26% and anterolateral thigh flaps in 74%. Overall, early complication rate was 30%, which 20% were fistulae (brachial-radial, 2.8%; ALT free flap, 8.3%). Late complications (20%) included stenosis and distal graft lumen obstruction. Only 10% of patients were unable to tolerate oral feeding and 50% of this patient needed permanent gastrostomy. Regarding oncological follow-up during the 24-month post-operative, no tumor recurrence was observed. Functional outcomes of reconstruction with brachial-radial and ALT flap were satisfying. Our findings suggest that ALT has a lower incidence of post-operative complications than radial forearm flap. The choice of the type of flap will depend on the size and location of the defect. Small and partially covered defects benefit from the use of a radial flap, and for larger and circumferential pharyngeal reconstructions with possible radiotherapy requirements, they benefit from an ALT flap.


Conceptual processing effects on automatic memory.
In the present study, influences of conceptual processing on automatic forms of memory were investigated, using a category production task. The experiment employed Jacoby's (1991) process dissociation procedure and fits of multinomial models to estimate conscious and automatic memory for semantic and graphemic study tasks. Memory estimates from a generate-source model indicated more automatic memory for semantic than for graphemic items on the category production task. These results provide support for conceptual processing influences on automatic forms of memory.


Adolescents born prematurely with isolated grade 2 haemorrhage in the early 1990s face increased risks of learning challenges.
To compare the impact of low-grade haemorrhage on neurocognitive function in 16-year-old adolescents born preterm, by grade of intraventricular haemorrhage, and term controls. We evaluated 338 preterm adolescents (birth weight 600-1250 g) for intelligence, executive function and memory tasks. Eleven had grade 3-4 haemorrhage, 44 had grade 2, 31 had grade 1, and 251 had no haemorrhage. Group comparisons were made with 102 term age-matched controls, and regression models used to identify the risk that low-grade haemorrhage posed for cognitive, executive function and memory deficits. Preterm adolescents with grade 2 haemorrhage had higher deficit rates of verbal intelligence, receptive vocabulary, phonemic fluency, cognitive flexibility and phonological fluency than preterm adolescents with grade 1 or no haemorrhage, compared with term controls. After excluding preterm adolescents with both grade 2 haemorrhage and cystic periventricular leukomalacia, those with isolated grade 2 haemorrhage remained at greater risk of cognitive and executive function deficits than term controls and of cognitive deficits than preterm adolescents with no haemorrhage. Our findings suggest that preterm adolescents born in the early 1990s with isolated grade 2 haemorrhage are at increased risk of learning challenges, including cognitive and executive function deficits.


Perfusion abnormalities in mild cognitive impairment and mild dementia in Alzheimer's disease measured by pulsed arterial spin labeling MRI.
Alzheimer's disease (AD) and mild cognitive impairment (MCI), the transitional clinical stage between cognition in normal aging and dementia, have been linked to abnormalities in brain perfusion. Pulsed arterial spin labeling (PASL) is a magnetic resonance imaging (MRI) technique for evaluating brain perfusion. The present study aimed to determine regional perfusion abnormalities in 19 patients with mild dementia in AD and 24 patients with MCI as compared to 24 cognitively healthy elderly controls using PASL. In line with nuclear imaging methods, lower perfusion in patients with MCI and AD was found mainly in the parietal lobe, but also in angular and middle temporal areas as well as in the left middle occipital lobe and precuneus. Our data imply that PASL may be a valuable instrument for investigating perfusion changes in the transition from normal aging to dementia and indicate that it might become an alternative to nuclear imaging techniques in AD diagnostics.


Molecular characterization of four novel mutations causing factor VII deficiency.
Hereditary deficiency of factor VII (FVII) is a rare coagulation defect. We previously studied the molecular basis of the FVII deficiency in Israeli patients and found that the majority of them bore the Ala244Val mutation. In the present study we further analysed FVII deficient patients. Three patients with severe FVII deficiency (FVII activity < or =1%) and one with partial deficiency (25%) were studied. In all four patients, the FVII gene was amplified and sequenced. Four novel mutations have been identified: IVS 2+1G-->C Phe 24 deletion, Leu300Pro and Arg277His. Homozygosity for the IVS2+1G-->C mutation was lethal, whereas homozygosity for the Phe 24 deletion was accompanied by a severe bleeding tendency. FVII modeling showed that Phe 24 is located in the Gla domain. Both Arg 277 and Leu 300 are within the catalytic domain, although Arg 277 is also involved in tissue factor binding. We have analysed four mutations, two of which (IVS2+1G-->C, Phe 24 deletion) were associated with severe bleeding tendency in the homozygous state, facilitating prenatal diagnosis. Hypothetically, using FVII modeling, Arg 277 replacement by histidine may weaken the tissue factor, while deletion of Phe 24 and Leu300Pro mutation might be associated with abnormal folding of the Gla and catalytic domains, respectively.


Tailor-Made Dispersion and Distribution of Stereocomplex Crystallites in Poly(l-lactide)/Elastomer Blends toward Largely Enhanced Crystallization Rate and Impact Toughness.
Stereocomplex (SC) crystallites, formed between poly(l-lactide) (PLLA) and poly(d-lactide), exhibit great potential to substantially enhance crystallization rate of PLLA-based materials as an eco-friendly nucleating agent. However, the nucleation efficiency of the SC crystallites is still far below an expected level, mostly on account of their strong aggregation tendency in PLLA/PDLA melts. Herein, taking PLLA/poly(ethylene-methyl acrylate-glycidyl methacrylate) (E-MA-GMA) blends as an example, we report a unique and facile strategy to control the dispersion and distribution of SC crystallites within the PLLA matrix by using elastomeric E-MA-GMA as carrier for the incorporation of PDLA. To do this, PDLA was first blended with E-MA-GMA or chemically grafted onto the E-MA-GMA. During subsequent melt-blending of PLLA and the E-MA-GMA/PDLA master batch, the PDLA chain clusters predispersed in the E-MA-GMA phase can gradually migrate into PLLA matrix and then collaborate with the matrix chains to form large amounts of tiny and well-dispersed SC crystallites. Compared with the SC-crystallite agglomerates formed by the direct melt-blending of PLLA and PDLA components, such tiny SC crystallites are much more effective in accelerating PLLA matrix crystallization. More interestingly, when PDLA chains are grafted onto the EMA-GMA, the formed SC crystallites tend to preferentially distribute at the blend interface and thus induce not only optimal nucleation efficiency but also superior impact toughness because these interface-localized SC crystallites can also serve as bridges to enhance interface adhesion. This work could open a new avenue in designing heat-resistant and supertough PLLA blends via controllable construction of SC crystallites.


Physical activity in primary versus secondary prevention indication implantable cardioverter defibrillator recipients 6-12 months after implantation - a cross-sectional study with register follow up.
To describe physical activity status among patients with implantable cardioverter defibrillators (ICDs) according to the indication for ICD implant compared with international guidelines and compared with a matched healthy reference population to detect potential for improved physical outcomes; to describe patients' beliefs regarding participation in physical exercise by ICD indication; to describe factors predicting low physical activity; and to describe physical activity as a predictor of mortality. National survey with register follow-up. Comparisons were made to a matched healthy reference population, and patients were followed in registers for 15 months. Patients are identified from national registers and questionnaires are distributed by postal mail. All diagnostic profiles and indications were included as were both single-chamber ICD and biventricular ICD (N=499). Not applicable. Questions regarding physical activity and the International Physical Activity Questionnaire-Short Form were used to assess physical activity. The response rate was 71.7%. The mean age of participants was 65.5 years, with 82% of participants being men. Of the participants, 37% participated in a rehabilitation program, and 21% were sedentary compared with 8% in the reference population (P<.0001). Only 13% of patients followed physical exercise guidelines. Low physical activity was predicted by primary prevention indication (odds ratio [OR]=2.5; 95% confidence interval [CI], 1.3-4.7) and higher comorbidity (OR=2.1; 95% CI, 1.0-4.1; P<.05). Finally, low physical activity was associated with increased mortality (OR=3.9; 95% CI, 1.11-13.71; P<.05); however, it was not statistically significant when adjusted for age, sex, marital status, and comorbidity. Guidelines for exercise and participation in rehabilitation are not met for this population, leaving a great potential for future interventions to improve the clinical outcomes, which are modifiable by exercise.


Extraction of phenolic compounds: A review.
Phenolic compounds are parts of secondary metabolites mostly found in plant species with enormous structural diversities. They can exist as glycosides or aglycones; matrix or free-bound compounds; and comprising mostly polymerized or monomer structures. Additionally, these compounds are not universally dispensed within plants with varied stability. This has contributed to challenging extraction processes; implying that employing a single step or inappropriate extraction technique might change the recovery of phenolic components from the plant samples. Hence, it is important to select an appropriate extraction method so as to recover the targeted phenolic compounds. This is will helps to recover substantial yields from the sample matrix. Therefore, this review mainly focuses on the phenolic compounds and several methods of extraction that are used to obtaining them from plant materials. These extraction methods includes both conventional and unconventional techniques.


Intra- and extracellular domains of the Helicoverpa armigera cadherin mediate Cry1Ac cytotoxicity.
Diverse midgut cadherin mutations confer resistance to Cry1A toxins in at least three lepidopteran pests, including the cotton bollworm, Helicoverpa armigera. Most of these cadherin mutations are inherited as recessive alleles and result in changes within the cadherin repeat (CR) regions of the extracellular protein domain. However, the H. armigera r15 cadherin mutation results in a deletion of 55 amino acid residues within the cytoplasmic domain, and Cry1A resistance is inherited as a non-recessive trait. Here, eight recombinant H. armigera cadherin (HaCad) proteins, including seven variants containing different combinations of CRs and the cytoplasmic domain, were expressed in cultured insect cells using a baculovirus expression system and were analyzed for Cry1Ac binding and toxicity. Cells expressing either the wild-type HaCad or a mutant lacking only the region corresponding to the first nine CRs bound Cry1Ac and were equally susceptible to Cry1Ac. Cells expressing mutant HaCad proteins without the Cry1A toxin binding region (TBR) located in the CR nearest the plasma membrane did not bind Cry1Ac and were not killed by the toxin. Among the mutant proteins, loss of toxicity was observed in all cells producing HaCad variants lacking the amino acids 1422-1440, indicating that this TBR motif is important for both toxin binding and to confer susceptibility to Cry1Ac. Cells expressing the HaCad variant lacking the entire cytoplasmic domain retained Cry1Ac binding, but were significantly less susceptible to Cry1Ac than the cells producing either wild-type HaCad or HaCad lacking the first nine CRs. These results suggest that both the extracellular and the cytoplasmic domains of HaCad participate in Cry1Ac intoxication.


Tris(methylammonium thiocyanurate) monohydrate.
In the title compound, 3[(CH(3))(3)HN(+)]·3C(3)H(2)N(3)S(3) (-)·H(2)O, two independent trithio-cyanurate anions construct a planar hydrogen-bonded ribbon with two N-H⋯S hydrogen bonds linking each pair of adjacent anions in the chain. The third independent anion and the water mol-ecule form a chain by way of N-H⋯S and O-H⋯S contacts, which propagates parallel to the ribbon. The chains and ribbons are cross-linked by O-H⋯S hydrogen bonds, generating sheets. The three independent trimethyl-ammonium cations are contained between the sheets by way of various N-H⋯S and N-H⋯N contacts.


Appropriate Use of Antibiotics for the Management of Respiratory Tract Infections.
Lower Respiratory Tract Infections (LRTIs) and Upper Respiratory Tract Infections (URTIs) cause high morbidity and mortality worldwide. Lower respiratory tract infections are generally more serious than upper infections. Antibiotics are often inappropriately prescribed for patients with RTI. Inappropriate utilization of antibiotics, specifically the broad spectrum in respiratory tract infection, results in resistance to antibiotics. The common use of antibiotics is the prime reason for the spread of drug-resistant bacterial strains, which not only results in expensive treatments but also causes a high rate of morbidity and mortality due to undesired adverse effects of the drug. A literature survey was performed using PubMed, Science Direct, and Web of Science search engines. One hundred forty-five papers were retrieved, and more than 100 were included in this review. This article describes the overview and diagnosis of respiratory tract infections and the plethora of antibiotics that have been used in the management of RTIs.


The CYTOLD and ERTOLD pathways for lipid droplet-protein targeting.
Lipid droplets (LDs) are the main organelles for lipid storage, and their surfaces contain unique proteins with diverse functions, including those that facilitate the deposition and mobilization of LD lipids. Among organelles, LDs have an unusual structure with an organic, hydrophobic oil phase covered by a phospholipid monolayer. The unique properties of LD monolayer surfaces require proteins to localize to LDs by distinct mechanisms. Here we review the two pathways known to mediate direct LD protein localization: the CYTOLD pathway mediates protein targeting from the cytosol toLDs, and the ERTOLD pathway functions in protein targeting from the endoplasmic reticulum toLDs. We describe the emerging principles for each targeting pathway in animal cells and highlight open questions in the field.


Online hemodiafilteration use in children: a single center experience with a twist.
Haemodiafilteration (HDF) is a promising new modality of renal replacement therapy (RRT). It is an improvement in the quality of hemodialysis (HD) and thus in the quality of patients'lives. The main obstacle to using HDF is the cost, especially in developing countries. The purpose of this study was to evaluate the benefits of incorporating HDF with different regimens in the treatment of children with end stage renal disease (ESRD). Thirty-four children with ESRD on regular HD in Pediatric Dialysis Unit, Children's Hospital, Ain Shams University were followed up in 2 phases: initial phase (all patients: HD thrice weekly for 3 months) and second phase, patients were randomized into 2 groups, HDF group and HD group, the former was subdivided into once and twice weekly HDF subgroups. Evaluation using history, clinical and laboratory parameters at 0, 3, 9 and 18 months was carried out. On short term, we found that the HDF group was significantly superior to HD group regarding all clinical and laboratory parameters. Also, twice HDF subgroup was significantly superior to once HDF subgroup. This was confirmed on long term follow up, but the once HDF proved comparable to twice subgroup. Incorporating online hemodiafilteration (OL-HDF) in the RRT of children was beneficial in most of the clinical and laboratory parameters measured. It's not all or non; OL-HDF, even once a week, can improve outcomes of HD without significantly affecting the cost.


Progesterone receptors in the oviduct of a viviparous snake (Nerodia): correlations with ovarian function and plasma steroid levels.
The physiological significance of progesterone during gestation in viviparous reptiles is not understood, although there is strong evidence for luteal synthesis and secretion of this steroid. In a previous study we characterized an oviduct progesterone receptor in the viviparous snake, Nerodia, and in this study we describe changes in receptor during the reproductive cycle. Correlation of the amount of receptor with changes in plasma estradiol 17 beta and progesterone and the effect of injected hormones suggest that the receptor may be regulated by these steroids as in mammals. Thus, the basis exists for target organ responses to progesterone and provides additional evidence for the potential role of progesterone in the early hormonal adaptations in the evolution of viviparity.


Radiological features characterising indeterminate testes masses: a systematic review and meta-analysis.
The use of scrotal ultrasonography (SUS) has increased the detection rate of indeterminate testicular masses. Defining radiological characteristics that identify malignancy may reduce the number of men undergoing unnecessary radical orchidectomy. To define which SUS or scrotal magnetic resonance imaging (MRI) characteristics can predict benign or malignant disease in pre- or post-pubertal males with indeterminate testicular masses. This systematic review was conducted in accordance with Cochrane Collaboration guidance. Medline, Embase, Cochrane controlled trials and systematic reviews databases were searched from (1970 to 26 March 2021). Benign and malignant masses were classified using the reported reference test: i.e., histopathology, or 12 months progression-free radiological surveillance. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). A total of 32 studies were identified, including 1692 masses of which 28 studies and 1550 masses reported SUS features, four studies and 142 masses reported MRI features. Meta-analysis of different SUS (B-mode) values in post-pubertal men demonstrated that a size of ≤0.5 cm had a significantly lower odds ratio (OR) of malignancy compared to masses of >0.5 cm (P < 0.001). Comparison of masses of 0.6-1.0 cm and masses of >1.5 cm also demonstrated a significantly lower OR of malignancy (P = 0.04). There was no significant difference between masses of 0.6-1.0 and 1.1-1.5 cm. SUS in post-pubertal men also had a statistically significantly lower OR of malignancy for heterogenous masses vs homogenous masses (P = 0.04), hyperechogenic vs hypoechogenic masses (P < 0.01), normal vs increased enhancement (P < 0.01), and peripheral vs central vascularity (P < 0.01), respectively. There were limited data on pre-pubertal SUS, pre-pubertal MRI and post-pubertal MRI. This meta-analysis identifies radiological characteristics that have a lower OR of malignancy and may be of value in the management of the indeterminate testis mass.


Evaluating machine learning methodologies for identification of cancer driver genes.
Cancer is driven by distinctive sorts of changes and basic variations in genes. Recognizing cancer driver genes is basic for accurate oncological analysis. Numerous methodologies to distinguish and identify drivers presently exist, but efficient tools to combine and optimize them on huge datasets are few. Most strategies for prioritizing transformations depend basically on frequency-based criteria. Strategies are required to dependably prioritize organically dynamic driver changes over inert passengers in high-throughput sequencing cancer information sets. This study proposes a model namely PCDG-Pred which works as a utility capable of distinguishing cancer driver and passenger attributes of genes based on sequencing data. Keeping in view the significance of the cancer driver genes an efficient method is proposed to identify the cancer driver genes. Further, various validation techniques are applied at different levels to establish the effectiveness of the model and to obtain metrics like accuracy, Mathew's correlation coefficient, sensitivity, and specificity. The results of the study strongly indicate that the proposed strategy provides a fundamental functional advantage over other existing strategies for cancer driver genes identification. Subsequently, careful experiments exhibit that the accuracy metrics obtained for self-consistency, independent set, and cross-validation tests are 91.08%., 87.26%, and 92.48% respectively.


Pneumocystis pneumonia in COVID-19 patients: A comprehensive review.
The admitted patients of intensive care units with coronavirus disease 2019 (COVID-19) meet the challenges of subsequent infections. Opportunistic fungal infections such as Pneumocystis pneumonia (PCP) are among the important factors in the context of COVID-19 patients affecting illness severity and mortality. We reviewed the literature on COVID-19 patients with PCP to identify features of this infection. Although studies confirmed at least the presence of one immunosuppressive condition in half of PCP patients, this disease can also occur in immunocompetent patients who developed the immunosuppressive condition during Covid-19 treatment. The major risk factors associated with COVID-19 patients with PCP can be considered low lymphocyte counts and corticosteroid therapy. Diagnostic and treatment options are complicated by the overlapping clinical and radiologic characteristics of PCP and COVID-19 pneumonia. Therefore, physicians should comprehensively evaluate high-risk patients for PCP prophylaxis.


External oxidant-compatible phosphorus(III)-directed site-selective C-H carbonylation.
The first development of an external oxidant-compatible system involving a phosphorus(III)-directed C-H functionalization has been uncovered. An efficient C-H esterification of indoles with CO and alcohols has been reported in which the high reactivity and the exclusive C7-selectivity derives from the selection of a P(III)-directing group and the utilization of benzoquinone as an external oxidant with palladium catalysis. This strategy shows many advantages, involving an easily accessible and removable directing group, the use of cheap carbonylation sources, a broad substrate scope, and excellent positional selectivity. Two cyclopalladated intermediates were confirmed by x-ray analysis, uncovering key mechanistic features of this P(III)-directed C-H metalation event.


A strictly anaerobic nitrate-reducing bacterium growing with resorcinol and other aromatic compounds.
With resorcinol as sole source of energy and organic carbon, two stains of gram-negative, nitrate-reducing bacteria were isolated under strictly anaerobic conditions. Strain LuBRes1 was facultatively anaerobic and catalase- and superoxide dismutase-positive. This strain was affiliated with Alcaligenes denitrificans on the basis of substrate utilization spectrum and peritrichous flagellation. Strain LuFRes1 could grow only under anaerobic conditions with oxidized nitrogen compounds as electron acceptor. Cells were catalase-negative but superoxide dismutase-positive. Since this strain was apparently an obligate nitrate reducer, it could not be grouped with any existing genus. Resorcinol was completely oxidized to CO2 by both strains. Neither an enzyme activity reducing or hydrolyzing the resorcinol molecule, nor an acyl-CoA-synthetase activating resorcylic acids or benzoate was detected in cell-free extracts of cells grown with resorcinol. In dense cell suspensions, both strains produced a compound which was identified as 5-oxo-2-hexenoic acid by mass spectrometric analysis. This would indicate a direct, hydrolytic cleavage of the resorcinol nucleus without initial reduction.


Visceral Adipose Tissue is Negatively Associated With Bone Mineral Density in NHANES 2011-2018.
The relationship of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with bone mineral density (BMD) is not well established. To examine the associations of VAT and SAT with total body BMD in a large, nationally representative population with a wide range of adiposity. We analyzed 10 641 subjects aged 20 to 59 years in National Health and Nutrition Examination Survey 2011-2018 who had undergone total body BMD and had VAT and SAT measured by dual-energy X-ray absorptiometry. Linear regression models were fitted while controlling for age, sex, race or ethnicity, smoking status, height, and lean mass index. In a fully adjusted model, each higher quartile of VAT was associated with an average of 0.22 lower T-score (95% CI, -0.26 to -0.17, P < 0.001), whereas SAT had a weak association with BMD but only in men (-0.10; 95% CI, -0.17 to -0.04, P = 0.002). However, the association of SAT to BMD in men was no longer significant after controlling for bioavailable sex hormones. In subgroup analysis, we also found differences in the relationship of VAT to BMD in Black and Asian subjects, but these differences were eliminated after accounting for racial and ethnic differences in VAT norms. VAT has a negative association with BMD. Further research is needed to better understand the mechanism of action and, more generally, to develop strategies for optimizing bone health in obese subjects.


Can ICF model for patients with breast-cancer-related lymphedema predict quality of life?
The aim of the study was to investigate if the International Classification of Functioning, Disability and Health (ICF) model with clinical data from patients with breast-cancer-related lymphedema can predict their health-related quality of life (HRQL). Sixty-one patients with breast-cancer-related lymphedema were recruited. Data were collected from records, including age, type(s) of surgery, number of dissected lymph nodes and history of radiotherapy and/or chemotherapy, duration of lymphedema, and duration between surgery and enrollment. Excessive arm volume, average arm symptom, function of upper extremity (U/E), and HRQL were assessed four times during and after patients' treatment of lymphedema. The ICF model accounted for 20.5% to 55.6% variance in each domain of HRQL. Activity and participation reflected by U/E function were the most important factor, significantly predicting every domain of HRQL. Among measured impairments, average arm symptom was found to be most correlated with U/E function (r = 0.590, P < 0.05). The ICF model consisting of clinical measures for patients with breast-cancer-related lymphedema can predict their HRQL. Activity and participation were the most important component. Arm symptoms rather than arm volume significantly correlated with U/E function. This might suggest that reducing arm symptoms is relatively more important while treating patients with breast-cancer-related lymphedema.


Effect of hyperbaric oxygen therapy on osseointegration of titanium implants in irradiated bone: a preliminary report.
Four patients who had undergone combined surgical and radiotherapeutic treatment for maxillofacial cancer had osseointegrated titanium implants placed in the bone of the treated region at various intervals after irradiation. Preoperatively and postoperatively, hyperbaric oxygen therapy was administered to the patients at the level of 2 or 3 atmosphere absolute (ATA). Of the 21 fixtures placed, one was lost because of lack of osseointegration, rendering the survival rate 92.3%. Hyperbaric oxygen therapy seemed to be a viable method to improve the survival rate of fixtures in irradiated bone tissue.


Structure and biosynthesis of Lyt-1.
Two-dimensional chymotryptic peptide maps of Lyt-1.1 and Lyt-1.2 from Lyt-1 congenic thymocytes labeled with 125I in the usual way before lysis did not significantly differ, but there was a characteristic difference between maps of Lyt-1.1 and Lyt-1.2 obtained from 125I-labeled solubilized membrane fragments. We conclude that the Lyt-1 locus of chromosome 19 includes the protein-structural gene for Lyt-1. This conclusion is further supported by evidence with 35S-cysteine-labeled thymocytes: Thus an early 62K intermediate form, and a 60K form from tunicamycin-treated cells devoid of N-linked and O-linked carbohydrates, were precipitated by Lyt-1 alloantibody, which implies that the allo-specificity of Lyt-1 glycoprotein (67K) resides partly or wholly in protein.


Trends in malaria epidemiological factors following the implementation of current control strategies in Dangassa, Mali.
Over the past decade, three strategies have reduced severe malaria cases and deaths in endemic regions of Africa, Asia and the Americas, specifically: (1) artemisinin-based combination therapy (ACT); (2) insecticide-treated bed nets (ITNs); and, (3) intermittent preventive treatment with sulfadoxine-pyrimethamine in pregnancy (IPTp). The rationale for this study was to examine communities in Dangassa, Mali where, in 2015, two additional control strategies were implemented: ITN universal coverage and seasonal malaria chemoprevention (SMC) among children under 5 years old. This was a prospective study based on a rolling longitudinal cohort of 1401 subjects participating in bi-annual smear surveys for the prevalence of asymptomatic Plasmodium falciparum infection and continuous surveillance for the incidence of human disease (uncomplicated malaria), performed in the years from 2012 to 2020. Entomological collections were performed to examine the intensity of transmission based on pyrethroid spray catches, human landing catches and enzyme-linked immunosorbent assay (ELISA) testing for circumsporozoite antigen. A total of 1401 participants of all ages were enrolled in the study in 2012 after random sampling of households from the community census list. Prevalence of infection was extremely high in Dangassa, varying from 9.5 to 62.8% at the start of the rainy season and from 15.1 to 66.7% at the end of the rainy season. Likewise, the number of vectors per house, biting rates, sporozoites rates, and entomological inoculation rates (EIRs) were substantially greater in Dangassa. The findings for this study are consistent with the progressive implementation of effective malaria control strategies in Dangassa. At baseline (2012-2014), prevalence of P. falciparum was above 60% followed by a significant year-to-year decease starting in 2015. Incidence of uncomplicated infection was greater among children < 5 years old, while asymptomatic infection was more frequent among the 5-14 years old. A significant decrease in EIR was also observed from 2015 to 2020. Likewise, vector density, sporozoite rates, and EIRs decreased substantially during the study period. Efficient implementation of two main malaria prevention strategies in Dangassa substantially contribute to a reduction of both asymptomatic and symptomatic malaria from 2015 to 2020.


[Effect of hypothalamic lHRH (luliberin) on the electrical activity of isolated rat heart].
Decelerating effect of LH--RH upon the frequency of contraction of the rat isolated perfused heart was revealed. The neurohormone was also shown to change the heart electrical activity causing elongation of the systole due to an increase in repolarization period. Simultaneous application of LH--RH and norepinephrine to the rat isolated perfused heart did not alter the frequency of contractions. The LH--RH seems to take part in the regulation of the myocardium excitability by means of its effect on the membrane permeability for monovalent cations.


Would they follow what has been laid down? Cancer patients' and healthy controls' views on adherence to advance directives compared to medical staff.
Advance directives are propagated as instruments to maintain patients' autonomy in case they can no longer decide for themselves. It has been never been examined whether patients' and healthy persons themselves are inclined to adhere to these documents. Patients' and healthy persons' views on whether instructions laid down in advance directives should be followed because that is (or is not) "the right thing to do", not because one is legally obliged to do so, were studied and compared with that of medical staff. Vignette study presenting five cases. Cancer patients, healthy persons, nursing staff and physicians (n = 100 in each group) were interviewed. An adherence score was calculated (maximum value 5). The adherence score is found to be low in all groups, yet lowest in patients (1.55; standard deviation 1.13) and healthy controls (1.60; 1.37). The scores are significantly different between nursing staff on the one hand and patients and healthy controls on the other (p < 0.005 and p < 0.05, respectively), and between doctors and patients (p < 0.05). Interviewees who want these documents to be followed tend to live alone and to have already written an advance directive. Cancer patients and healthy persons widely disregard instructions laid down in advance directives and consider them less binding than physicians and nursing staff do. Only a minority tends to adhere more to advance directives. To improve decision-making at the end of life when patients are no longer able to decide for themselves alternative concepts, such as advanced care planning, should be considered.


Subdivision of frontal cortex mechanisms for language production in aphasia.
Ventrolateral prefrontal cortex (VLPFC) has long been linked to language production, but the precise mechanisms are still being elucidated. Using neuropsychological case studies, we explored possible sub-specialization within this region for different linguistic and executive functions. Frontal patients with different lesion profiles completed two sequencing tasks, which were hypothesized to engage partially overlapping components. The multi-word priming task tested the sequencing of co-activated representations and the overriding of primed word orders. The sequence reproduction task tested the sequencing of co-activated representations, but did not employ a priming manipulation. We compared patients' performance on the two tasks to that of healthy, age-matched controls. Results are partially consistent with an anterior-posterior gradient of cognitive control within lateral prefrontal cortex (Koechlin & Summerfield, 2007). However, we also found a stimulus-specific pattern, which suggests that sub-specialization might be contingent on type of representation as well as type of control signal. Isolating such components functionally and anatomically might lead to a better understanding of language production deficits in aphasia.


Nephrogenic adenoma: benign proliferative lesion of urothelium.
Three new cases of a rare benign proliferative lesion of the urothelium (nephrogenic adenoma) are hereby added to the existent 58 reported cases. All 3 lesions occurred in the bladder. Two of the 3 cases presented with a history of surgical interventions on the bladder, and the third patient had a history of chronic cystitis and pyelonephritis, and was on chronic dialysis. Diagnosis was made on histologic examination of cystoscopic biopsy of the lesions. Transurethral resection and/or fulguration was the treatment of choice. There was no recurrence of the lesions on follow-up cystoscopic examination.


Primary malignant melanoma of the scrotum: case report and literature review.
Malignant melanoma of the scrotum is the rarest of primary genitourinary melanomas, with only 3 cases reported previously. We present an additional case of this often aggressive malignancy. The pertinent literature is reviewed and the current management strategies are discussed.


The prognostic value of long-term visit-to-visit blood pressure variability on stroke in real-world practice: a dynamic cohort study in a large representative sample of Chinese hypertensive population.
The prognostic significance of long-term visit-to-visit blood pressure variability (BPV) has not yet been validated in "real world" hypertensive patients. The aim of the current study is to explore the prognostic value of BPV on stroke in hypertensive patients. This was a dynamic prospective cohort study based on electronic medical records in Shanghai, China. Hypertensive patients (N=122,636) without history of stroke at baseline, were followed up from 2005 to 2011. The cohort comprised of 4522 stroke patients and 118,114 non-stroke patients during a mean follow-up duration of 48 months. BPV was measured by standard deviation (SD) and the coefficient of variation (CV) of blood pressure. The visit-to-visit variability of both systolic blood pressure (SBP) and diastolic blood pressure (DBP) was independently associated with the occurrence of stroke [SD: the hazard ratios (95% confidence intervals) of SBP and DBP were 1.042 (1.021 to 1.064) and 1.052 (1.040 to 1.065); CV: the hazard ratios (95% confidence intervals) of SBP and DBP were 1.183 (1.010 to 1.356) and 1.151 (1.005 to 1.317), respectively]. The hazard ratio values increased along with an increase of the BPV levels of SBP and DBP. The increment effect remained significant after controlling the blood pressure control status of subjects. Increased BPV of both SBP and DBP, independent of the average blood pressure, is a predictor of stroke among community hypertensive patients in real-world clinical practice. The risk of stroke increased along with increased BPV. Stabilizing BPV might be a therapeutic target in hypertension.


COVID-19 impact on anxiety and depression in head and neck cancer patients: A cross-sectional study.
To evaluate whether the coronavirus disease 2019 has increased anxiety, depression, and distress levels in head and neck cancer (HNC) patients undergoing radiotherapy (RT). In this cross-sectional study, RT-HNC patients were surveyed using the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression and the distress thermometer (DT) for distress. HADS scores were compared with data pre-COVID-19. Additionally, we evaluated the COVID-19 impact on daily routines, treatment, and cancer care through a questionnaire. Fifty patients were included. The HADS mean score and estimated rates were 4.34 (±4.06)/22% for anxiety and 5.08 (±4.82)/22% for depression; in comparison, our historical control had 4.04 (±3.59)/20% for anxiety (p = .79) and 4.03 (±3.62)/17% for depression (p = .49). Mean DT score was 3.68 (±2.77). Responders were aware of COVID-19, afraid of having medical complications, believed it was life-threatening, did not miss appointments, believed their treatment was not impacted, and felt safe at the hospital amid the pandemic. This study suggests that anxiety, depression, and distress levels found in RT-HNC patients did not increase during the pandemic. Patients were afraid of being infected by COVID-19; however, they complied with their cancer treatment.


[Monoclonal antibodies in [corrected] development in [corrected] multiple sclerosis].
The last fifteen years have see the gradual appearance of a number of different drugs that have been shown to be effective as disease modifying therapies in multiple sclerosis. The opening and subsequent widening of the therapeutic armamentarium in multiple sclerosis will continue on a expanding course in the next few years due to the already known positive results of phase III clinical trials with orally administered molecules. Along with these, we have also seen the appearance of a group of drugs which, instead of being defined by their route of administration, are considered together as a consequence of their similar design: the monoclonal antibodies. The principal safety and efficacy results of three of the monoclonal antibodies that have already obtained positive results in phase II studies will be reviewed in this paper: alemtuzumab, rituximab / ocrelizumab, and daclizumab. For the preparation of this paper, information was obtained from already published articles and from the following web pages: www.clinicaltrials.gov of the National Institute of Health of the U.S.A., the EMA (European Medicines Agency) web page and the Spanish Medicines Agency (Agencia Española del Medicamento) web page. Final results from the phase III clinical trials in progress are required to produce definitive statements on the efficacy and safety of the reviewed drugs. However, and subject to confirmation of the presently available data from phase II trials, it is likely that this group of drugs is to be placed one step beyond the currently available disease-modifying therapies in terms of efficacy, but with a safety pattern which will make careful monitoring of treated patients a mandatory requirement so as to obtain adequate risk/benefit profiles.


Accessible and affordable healthcare? Views of Australians with and without chronic conditions.
With 50% of Australians having chronic disease, health consumer views are an important barometer of the 'health' of the healthcare system for system improvement and sustainability. To describe the views of Australian health consumers with and without chronic conditions when accessing healthcare. A survey of a representative sample of 1024 Australians aged over 18 years, distributed electronically and incorporating standardised questions and questions co-designed with consumers. Respondents were aged 18-88 years (432 males, 592 females) representing all states and territories, and rural and urban locations. General practices (84.6%), pharmacies (62.1%) and public hospitals (32.9%) were the most frequently accessed services. Most care was received through face-to-face consultations; only 16.5% of respondents accessed care via telehealth. The 605 (59.0%) respondents with chronic conditions were less likely to have private health insurance (50.3% vs 57.9%), more likely to skip doses of prescribed medicines (53.6% vs 28.6%), and miss appointments with doctors (15.3% vs 10.1%) or dentists (52.8% vs 40.4%) because of cost. Among 480 respondents without private health insurance, unaffordability (73.5%) or poor value for money (35.3%) were the most common reasons. Most respondents (87.7%) were confident that they would receive high quality and safe care. However, only 57% of people with chronic conditions were confident that they could afford needed healthcare compared with 71.3% without. Health consumers, especially those with chronic conditions, identified significant cost barriers to access of healthcare. Equitable access to healthcare must be at the centre of health reform.


Epidemiology of major childhood adversities and its effect on depression and suicide attempts in Chinese college students.
Childhood adversity is related to poor mental health outcomes in adulthood. However, few studies have examined the epidemiology of major childhood adversities and their effects on depression and suicide attempts in Chinese college students. 2755 students completed a questionnaire of 10 items about major childhood adversities, one item about suicide attempts, and the Zung self-rating depression scale. Single-factor analysis and multivariate logistic regression analysis were used to explore the association between different types of adversity/different numbers of types of adversity and suicide attempts/depression. 1916 (69.55%) respondents reported they had experienced major childhood adversities. Multivariate logistic regression analysis showed that witnessing a crash or murder, abuse by family members, and abuse by other adults or children were positively related to suicide attempts (OR: 1.712-2.222, all p<0.05). Abuse by other adults or children (OR=1.648, p<0.05) and serious injury during childhood (OR=1.494, p<0.05) were risk factors for depression. Those who had experienced 3 or more types of adversity were more likely to have depression (OR=1.806, p=0.002)and to have committed suicide attempts (OR= 3.307,p<0.001)compared to those without any adversities. The incidence of major childhood adversity is high among Chinese college students. Childhood adversity increases the risk of depression and suicide attempts. As the number of types of childhood adversity experienced by an individual increases, their risk ratio for suicide attempts and depression increases. To promote mental health, special attention should be given to those who have suffered childhood adversities.


Properties of modified surface for biosensing interface.
Properties of modified surface, behavior against salting-out effect, suppressive effect for protein nonspecific adsorption, and wettability were examined using various mercapto compounds bearing methyloligoethylene glycol, oligoethylene glycol, alkyl oligoethylene glycol, alkyl phosphoryl choline, alkyl inverse phosphoryl choline, and alkyl sulfobetaine moieties. The behavior against salting-out effect was examined using gold nanoparticle with PBS and NaCl aqueous solution. The suppressive effect for protein nonspecific adsorption was evaluated by SPR, and the wettability was measured on the SPR chip. The gold nanoparticle modified with 8C3EG, 12C4EG, 12CPC, 6CCP, and 12CCP showed excellent behavior against salting-out effect. The suppression of protein nonspecific adsorption was effective with 6EG, 12C4EG, 12CPC, and 12CS. On the other hand, the modified surface possessed high wettability except for the surface modified with M6EG. The results indicate that incorporation of alkyl group into surface modification materials is effective for the enhancement of behavior against salting-out effect and suppressive effect for protein nonspecific adsorption regardless of wettability. Among the zwitter ionic derivatives, inverse phosphoryl choline derivatives showed intriguing properties, high behavior against salting-out effect with high wettability but low suppressive effect for protein nonspecific adsorption.


Management of ground-glass opacities and sub-solid pulmonary nodules: a surgeon's perspective.
The regular use of high-resolution computed tomogram scans has led to an increase in the detection of asymptomatic ground-glass opacities and sub-solid nodules at an early stage. Different growth patterns of these lesions are making decision-making a real challenge. With growing experience and improving radiology interventions, management of these lesions is changing constantly. However, with variations in growth patterns and outcomes, immediate treatment options as well as follow-up surveillance and subsequent interventions can be confounding for the clinicians. This mini review describes algorithms for managing these ground-glass opacities (GGOs) and sub-solid nodules (SSNs) with a focus on the surgical options.


Detection of immune-related adverse events by medical imaging in patients treated with anti-programmed cell death 1.
Programmed death receptor-1 blocking antibodies (anti-PD1) are a new standard of care in many cancer types. Patients benefit from improved survival but have the risk of immune-related adverse events (irAE). We evaluated if medical imaging procedures, used for anti-tumour response assessment, can detect irAEs. All consecutive patients treated with anti-PD1 and with a medical imaging acquisition performed within 2 weeks with irAEs ≥2 were retrospectively included. Data were gathered from June 2014 to February 2017, and a central review was performed. The primary and secondary end-points were i) to evaluate the overall detection rate of irAEs by medical imaging and ii) to provide a comprehensive radiological description of irAEs. Fifty-three patients (31 women, 22 men; average age: 61 years) were included. The primary tumour was melanoma (n = 32), lung cancer (n = 18) and other (n = 3). Patients were treated with nivolumab (n = 27) or pembrolizumab (n = 26). Of 74 medical imaging procedures analysed (ratio = 1.4 medical imaging per patient), 55 irAE were detected. The detection rate was overall: 74% (95 confidence interval: 63-84%), positron emission tomography with 18F-fludeoxyglucose integrated with computed tomography (18F-FDG PET/CT): 83% (n = 10/12), magnetic resonance imaging: 83% (n = 5/6), computed tomography scan: 79% (n = 19/24), ultrasonography: 70% (n = 19/27), standard X-rays: 40% (n = 2/5), lung/mediastinum: 100% (n = 7/7), enterocolitis: 100% (n = 8/8), hypophysitis: 100% (n = 3/3), thyroiditis: 75% (n = 15/20), hepatitis: 67% (n = 2/3), arthralgia or arthritis: 40% (n = 2/5) and pancreas: 28% (n = 2/7). Medical imaging detected 74% of irAE in patients treated with anti-PD1. Beyond response assessment, medical imaging can detect irAE and guide towards specific management. We described the most frequent sites and patterns of imaging findings.


Aberrant origin of bilateral vertebral arteries associated with bovine aortic arch.
Variance of aortic arch branches are clinically significant as they are encountered in multiple endovascular treatments. The knowledge of different variants is crucial to perform successful vascular interventions. We report a novel anatomical variant of aortic arch found on contrast-enhanced computed tomography scan during a workup of cervical lymphadenopathy. The CT neck revealed a bovine aortic arch with an aberrant origin of bilateral vertebral arteries from the aortic arch. The right vertebral artery arose between the bovine trunk and the left subclavian artery, while the left vertebral artery was present distal to the left subclavian artery. This article sheds light on the potential clinical significance of these various types of aortic arch branches. Knowing the exact type of variant is particularly important in patient undergoing management involving carotid and surrounding vessels.


Total laryngectomy for squamous cell carcinoma: recognizing disease patterns to aid detection of tumor recurrence.
Posttreatment head and neck scans are among the most difficult to read due to the potentially complex surgical resection and reconstruction performed and additional radiation therapy changes. We aimed to determine the most common patterns and the timing of tumor recurrence following total laryngectomy for squamous cell carcinoma (SCCa). Retrospective review of imaging studies from January 2005 to May 2013 of patients with recurrent disease following prior total laryngectomy for locally advanced or locally recurrent SCCa. Patients were only included if recurrence was pathologically proven. Twenty-one patients met inclusion criteria in the study period. The median time to recurrence following laryngectomy was 13.3 months (range, 1-138 months). Recurrences were most common locoregional to the resection site. The most common site of recurrence as a distant metastasis was the lung. In addition, many patients demonstrated recurrent disease at multiple sites. Four patients demonstrated a second recurrence after salvage therapy of the first, 75% of whom had lung metastases. Subgroup analyses revealed a more rapid average time to nodal recurrence (median: 9.4 months, standard deviation: 5.2) than local recurrence (median: 12.0 months, standard deviation: 37.3). Lung metastases had the longest time to recurrence (median: 20.0 months, standard deviation: 20.5). Trends of location-specific temporal recurrence for SCCa following total laryngectomy may help the interpreting radiologist to more carefully evaluate particular sites based on the postsurgical time frame. Specifically, in the first 12 months lymph nodes and the surgical anastomoses should be carefully evaluated for new masses. Pulmonary metastases were found with a median onset of 20 months.


Subclavian artery pseudoaneurysm long after the division of modified Blalock-Taussig shunt.
A massive but asymptomatic left subclavian artery pseudoaneurysm was diagnosed in a 30-year-old female patient with transposition of the great arteries, ventricular septal defect, and pulmonary atresia. After undergoing bilateral modified Blalock-Taussig shunts at the age of 4 months and 3 years, respectively, she underwent the Rastelli operation and division of both shunts at the age of 6 years of age. The pseudoaneurysm was not discovered at the follow-up investigation at age 14. During the time period from age 18 to 30 years, she was lost to follow-up, she was confirmed to be free from infectious disease, traumatic accident, or vasculitis. Pregnancy-induced hypertension was not associated during her pregnancy. Graft replacement of the left subclavian artery and redo right ventricular outflow tract reconstruction were successfully performed under deep hypothermic circulatory arrest at the age of 33 years.


[Circulatory arrest after combined intravenous drugs for the treatment of orthodromic circular tachycardia of Wolff-Parkinson-White syndrome].
Antiarrhythmic drugs administered intravenously run the risk of producing a hemodynamic collapse even when used by expert and well trained hands. The arrhythmias in the focal point of a preexcitation syndrome constitute a very special situation in which extreme caution must be used when using intravenous drugs, because the conduction through accessory channels can vary, depending on multiple factors. We describe a case of a patient with an accessory atrioventricular pathway and orthodromic tachycardia who developed cardiac arrest by wide QRS tachycardia after receiving intravenous amiodarone.


Comparison of the optical coherence tomographic characters between acute Vogt-Koyanagi-Harada disease and acute central serous chorioretinopathy.
Acute Vogt-Koyanagi-Harada (VKH) disease and acute central serous chorioretinopathy (CSCR) are two common disorders with serous retinal detachment caused by dysfunction of choroid. The purpose of this study is to compare the morphological changes of these two diseases with spectral domain optical coherence tomography (SD-OCT). In this retrospective comparative study, the SD-OCT images of 65 eyes with acute VKH and 52 eyes with acute CSCR were reviewed for the presence of subretinal fluid, folds of retinal pigment epithelial (RPE), fluctuation of internal limiting membrane (ILM), subretinal septa, retinal pigment epithelium detachment (PED) and bulge of RPE. The foveal thickness was measured using the manual caliper of OCT software. The characteristics of SD-OCT were compared between two diseases. Subretinal fluid was present in both diseases. Folds of RPE, fluctuation of ILM, subretinal septa were seen only in VKH. Bulge of RPE presented only in CSCR. PED was more common in CSCR than in VKH (44.2% vs 3.1%, p < 0.001). The thickness of fovea and RPE undulation index were significantly greater in VKH compared to that in CSCR (746.7 ± 423.8 vs 444.9 ± 158.8 μm, p < 0.001 and 1.0667 ± 0.0509 vs. 1.0177 ± 0.0023, p = 0.003). Our study showed that although VKH and CSCR share similar features on SDOCT, there are characteristic differences between both disease entities.


[Primary torsion of the greater omentum. Apropos of a case and review of the literature].
The authors report about one case of acute abdominal pain syndrome, the etiology of which proved to be a primary torsion of the greater omentum. On this basis, they review the international literature and set forth etiopathogenetic hypotheses.


[Consent or the breadcrumb trail of care].
Consent must be sought by the doctor and caregivers on the basis of clinical insight. The argumentation must be coherent and well thought out, in order to facilitate the patient's choice. The question of consent is more important in psychiatry because of the different pathologies. The example of schizophrenia with the expression of delirium, hallucinations or disorganization reflects the difficulties encountered in the search for consent. This can then be apprehended as a therapeutic tool promoting meeting and trust.


A Mixed-Methods Investigation into Patients' Decisions to Attend an Emergency Department for Chronic Pain.
This study explored factors that underpin decisions to seek emergency department (ED) care for chronic noncancer pain in patients identifying as culturally and linguistically diverse (CALD) or Australian born. This mixed-methods study was underpinned by the Behavioral Model of Health Services Use conceptual framework. Consenting consecutive patients attending the ED for a chronic pain condition were recruited to a CALD (n = 45) or Australian-born (n = 45) cohort. Statistical comparisons compared the demographic, pain, health literacy, and episode of care profiles of both cohorts. Twenty-three CALD and 16 Australian-born participants consented to an audio-recorded semi-structured interview (n = 24) or focus group (n = 5 focus groups) conducted in their preferred language. Interviews were translated and transcribed into English for analysis using applied thematic analysis, guided by the conceptual framework. Data were triangulated to investigate the patterns of ED utilization and contributing factors for both cohorts. ED attendance was a product of escalating distress, influenced by the degree to which participants' perceived needs outweighed their capacity to manage their pain. This interaction was amplified by the presence of predisposing factors, including constrained social positions, trauma exposure, and biomedical health beliefs. Importantly, experiences varied between the two cohorts with higher degrees of pain catastrophizing, lower health literacy, and greater social challenges present for the CALD cohort. This study highlights the role contextual factors play in amplifying pain-related distress for CALD and Australian-born patients with chronic pain. The findings support a need for health care providers to recognize features of higher vulnerability and consider streamlining access to available support services.


Gaucher's disease: identification of novel mutant alleles and genotype-phenotype relationships.
A sequencing protocol for the acid beta-glucosidase (GCase) gene (GBA) was developed using a long-range PCR template. This protocol has an advantage of greater DNA yields over similar strategies. Seven Gaucher's disease patients had four novel and five other rare alleles. A non-pseudogene in-frame deletion (g.2600-2602delTAC) and a new complex mutation (null allele) were identified in Gaucher's disease type 1, i.e. the g.2600-2602delTAC deletion is associated with the non-neuronopathic variant. An F251L allele was found in a baby with the collodion skin phenotype. Three mutant alleles were identified in a single primary family with type 3. The patients' father at 45 years is healthy and is heteroallelic for the G202R and E326K alleles. Family studies indicated that E326K is in trans to G202R and L444P, and that isolated E326K is non-pathogenic in this family. A rare mutation R257Q was identified in a type 2 patient, providing an association with neuronopathic disease. A genotype L444P/L444P was noted in a 22-year-old non-neuronopathic patient. Complete gene sequencing showed a new complex allele consisting of L444P and g.7741T > C in the 3' UTR. Three additional complex alleles also involved the 3' UTR. Complete gene characterization in Gaucher's disease should allow greater insights into the correlation of specific alleles with phenotype.


Peri-anastomotic microdialysis lactate assessment after esophagectomy.
Esophagectomy is the cornerstone in curative treatment for esophageal and gastroesophageal junctional cancer. Esophageal resection is an advanced procedure with many complications, whereof anastomotic leak is the most dreaded. This study aimed to monitor the microcirculation with microdialysis analysis of local lactate levels in real-time on both sides of the esophagogastric anastomosis in totally minimally invasive Ivor-Lewis esophagectomy. Twenty-five patients planned for esophageal resection with gastric conduit reconstruction and intrathoracic anastomosis were recruited. A sampling device, the OnZurf® Probe, along with the CliniSenz® Analyser (Senzime AB, Uppsala Sweden) was utilized for measurements. Lactate levels from both sides of the anastomosis were analysed in real time, on site, by a transportable analyser device. Measurements were made every 30 min during the first 24 h, and thereafter every 2 hours for up to 4 days. All probes could be positioned as planned and on the third postoperative day 19/25 and 15/25 of the esophageal and gastric probes, respectively, continued to deliver measurements. In total, 89.6% (1539/1718) and 72.4% (1098/1516) of the measurements were deemed successful. The average lactate level on the esophageal side of the anastomosis and the gastric conduit ranged between 1.1-11.5 and 0.8-7.0 mM, respectively. Two anastomotic leaks occurred, one of which had persisting high lactate levels on the gastric side of the anastomosis. Application and use of the novel CliniSenz® analyser system, in combination with the OnZurf® Probe was feasible and safe. Continuous monitoring of analytes from the perianastomotic area has the potential to improve care after esophageal resection.