Derlin1 functions as an oncogene in cervical cancer via AKT/mTOR signaling pathway.
Cervical cancer (CC) ranks third in the morbidity and mortality of female cancer around the world. Derlin1 has been found to be overexpressed in several human cancers. However, it is still unclear about its roles in CC. The research aims to explore the relationship between Derlin1 and CC. We purchased a human CC tissues microarray, which contained CC tissues and corresponding para-cancerous tissues from 93 patients with primary cervical squamous cell carcinoma. Immunohistochemical staining was used to confirm the expression of Derlin1 in these tissues. And we detected the differential expression of Derlin1 in cervical cancer cell lines and normal cervical epithelial cells (H8). Further, the cervical cancer cell lines SiHa and C33A were used as an in vitro model, which was down-regulated the expression of Derlin1 using siRNA interference technology. The effects of Derlin1 down-regulating in CC cell lines on cell proliferation and migration were detected by CCK8 assay and transwell assay, respectively. The effect of Derlin1 down-regulating on apoptosis was analyzed by flow cytometry, and apoptosis-related proteins were detected using western blotting. In-depth mechanisms were studied using western blotting. In addition, the effects of Derlin1 up-regulating in normal cervical epithelial cells also were exposed. Derlin1 was significantly elevated in CC tissues (81.7%, 76/93), and the expression of Derlin1 was positively correlated with the tumor size, pathological grade, and lymph node metastasis in CC patients. And Derlin1 was high expressed in cervical cancer cell lines compared to H8 cells. Knockdown of Derlin1 in cervical cancer cell lines inhibited cell proliferation and migration. Moreover, knockdown of Derlin1 induced apoptosis and affected the expression of apoptosis-related proteins, including Bcl-2, Bax, Bim, caspase3 and caspase9. Further experiments showed that AKT/mTOR signal pathway might be involve in this processes that knockdown of Derlin1 inhibited the expression of p-AKT and p-mTOR. Over-expression of Derlin1 in H8 cells promoted cell proliferation and migration via up-regulated the expression of p-AKT and p-mTOR. Derlin1 is an oncogene in CC via AKT/mTOR pathway. It might be a potential therapeutic target for CC.


Prognostic significance of dysadherin expression in patients with non-small cell lung cancer.
The aim of this study was to evaluate the expression of dysadherin and E-cadherin and to investigate their clinical significance as prognostic factors in non-small cell lung cancer. Non-small cell lung cancer specimens were obtained from 131 patients undergoing clinically indicated operations at the Department of General and Cardiothoracic Surgery, Kanazawa University Hospital, between 1995 and 1997. All patients had undergone curative resection of the primary tumor, including systematic lymph node dissection. The avidin-biotin-peroxidase complex method was used for immunostaining of dysadherin and E-cadherin. Among the 131 lung cancer specimens, 46 (35.1%) tumors were positively stained with dysadherin. Preserved membranous E-cadherin staining was present in 45.8% (60/131) of cases. In this analysis dysadherin expression was not correlated with E-cadherin expression (P = .1333), but a significant association was observed between dysadherin expression and survival time. The overall survival of patients with dysadherin-positive tumors was significantly worse than that of those with dysadherin-negative tumors (P = .0059). Patients with reduced E-cadherin immunopositivity survived significantly shorter than those with preserved E-cadherin immunopositivity (P = .0406). The overall survival of patients with positive dysadherin and reduced E-cadherin expression was significantly worse than that of patients with negative dysadherin and preserved E-cadherin expression (P = .0002). Multivariate analysis revealed the independent prognostic value of dysadherin positivity, reduced E-cadherin expression, and lymph node metastasis on overall survival. Dysadherin expression is an independent prognostic factor of survival in patients with non-small cell lung cancer, and combined immunohistochemical analysis of dysadherin and E-cadherin expression might provide further prognostic information.


Officials' promotion expectation, corporate strategic deviance and corporate growth in China: The moderating effect of corporate ownership.
Government (especially local government) plays an important role in China's economic growth, the government is made up of officials, corporates are participants and the driving force of market economy, therefore, ignoring officials may not be able to directly explain the mechanism of corporate growth. This paper intends to discover how officials' promotion expectation may be beneficial for corporates-directly and/or indirectly via corporate strategic deviance-in terms of corporate growth. We conduct an empirical analysis of Chinese listed companies to test these arguments, the results show that officials' promotion expectation has a significantly positive impact on corporate growth; corporate strategic deviance has a mediating effect on the relationship between officials' promotion expectation and corporate growth; compared with non-state-owned enterprises, corporate strategic deviance has less influence on state-owned enterprises' growth. Our research generates a more comprehensive understanding of the political stakeholders-corporate growth relationship, provides direct evidence for the positive role of officials in corporate growth and expands the mediating research of corporate growth.


Assessing the protective effect of bentonite against lead toxicity in growing lambs.
The objective of the present experiment was to investigate the effect of bentonite supplementation in lead (Pb)-exposed lambs on serum Pb, Ca, P, Cu, Zn, and Fe concentrations, blood hematological parameters, and hepatic enzymes. Twenty Zandi male lambs (initial BW, 17.5 ± 1.6 kg) were randomly assigned to one of the four treatments: (1) control (no Pb or bentonite), (2) 15 mg/kg DM Pb as Pb acetate with no bentonite, (3) 15 mg/kg DM Pb as Pb acetate with 1.5% bentonite, and (4) 15 mg/kg DM Pb as Pb acetate with 3% bentonite. The experiment lasted after 90 days. Lead intake resulted in a decrease (P < 0.05) in serum Fe and an increase in serum Pb, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activities (P < 0.05). Bentonite supplementation at 1.5 or 3% of DM decreased blood Pb concentration (P < 0.01) in lambs fed diets containing Pb and reduced (P < 0.05) blood concentration of Cu and Zn compared to control group (P < 0.01). However, the hematological parameters were not affected by any of the treatments. Our results showed that the dietary supplementation of bentonite could protect lambs against lead toxicity.


Comparison of linkage maps from F2 and three times intermated generations in two populations of European flint maize (Zea mays L.).
Intermated mapping populations are expected to result in high mapping resolution for tightly linked loci. The objectives of our study were to (1) investigate the consequences of constructing linkage maps from intermated populations using mapping methods developed for F(2) populations, (2) compare linkage maps constructed from intermated populations (F(2)Syn3) with maps generated from corresponding F(2) and F(3) base populations, and (3) investigate the advantages of intermated mapping populations for applications in plant breeding programs. We constructed linkage maps for two European flint maize populations (A x B, C x D) by mapping 105 SSR markers in generations F(2) and F(2)Syn3 of population A x B, and 102 SSR markers in generations F(3) and F(2)Syn3 of population C x D. Maps for F(2)Syn3 were constructed with mapping methods for F(2) populations (Map A) as well as with those specifically developed for intermated populations (Map B). Both methods relate map distances to recombination frequencies in a single meiosis and, therefore, did not show a map expansion in F(2)Syn3 compared with maps constructed from the respective F(2) or F(3) base populations. Map A and B differed considerably, presumably because of theoretical shortcomings of Map A. Since loosely linked markers could not unambiguously be mapped in the F(2)Syn3 populations, they may hamper the construction of linkage maps from intermated populations.


Increased risk for substance use and health-related problems among homeless veterans.
The first aim of this study was to compare self-reported causes of homelessness between veterans and nonveterans. A second aim examined whether homeless male veterans were more likely than homeless male nonveterans to experience current problems with addictions, mental health, and physical health. Additionally, a third aim was to compare frequency of emergency room visits and treatment needs between the two groups. Secondary data analyses compared male homeless veterans and nonveterans (N = 353) enrolled in the Alachua County Point in Time study in central Florida. Participants completed a questionnaire on demographics and health variables. Additional questions included recent emergency room visits and medical or other needs not being met. Veterans reported higher rates of substance use and mental health problems as a primary cause of homelessness when compared to nonveterans. Homeless veterans were more likely than nonveterans to report current problems with addictions (OR = 6.29, 95% CI: 3.43-11.53, p < .001), mental health problems (OR = 4.12, 95% CI: 2.28-7.42, p < .001), and physical problems (OR = 1.83, 95% CI: 1.08-3.67, p < .01). Finally, over half of homeless veterans (53.1%) reported an ER visit in the past year compared to only 40.9% of nonveterans (OR = 1.73, 95% CI: 1.07-2.80, p < .05). Veterans may be more likely to become homeless due to addiction and mental health and over half of homeless veterans are presenting to hospital emergency rooms. Given the greater utilization among homeless veterans, emergency rooms may serve as a prime opportunity to provide brief treatment and referrals for needed services.


Do cyclodextrins bound to dextran microspheres act as sustained delivery systems of drugs?
The use of cyclodextrins (CDs) for controlled delivery of drugs is largely presented in the literature. However, the question of whether CDs themselves linked to a polymeric network are able to sustain the release of drugs still persists. Here, CD immobilization within dextran microspheres is reported, and CD-dextran complexes were packed in a glass column and then, the retention time of different drugs and drug model compounds was determined by liquid chromatography. The release profiles of drugs and of drug model compounds (indole, 3-nitrophenol, p-hydroxybenzoic acid, diclofenac), characterized by different values of the retention time (high, moderate or low), were investigated. The release rates were quite high even for drugs that exhibit very high retention time (high association equilibrium constant). Moreover, the volume of the release fluid strongly influences the rate of drug release. As a whole, "the sink conditions" must be continuously maintained, since at each drug concentration in the release medium, equilibrium occurs between the free and the CD-bound drug.


Acetal phosphatidic acids: novel platelet aggregating agents.
1 Palmitaldehyde, olealdehyde and linolealdehyde acetal phosphatidic acids induced rapid shape change and dose-dependent biphasic aggregation of human platelets in platelet-rich plasma; aggregation was reversible at low doses and irreversible at high doses of the acetal phosphatidic acids. The palmitaldehyde congener elicited monophasic dose-dependent aggregation of sheep platelets in platelet-rich plasma.2 The threshold concentration for palmitaldehyde acetal phosphatidic acid (PGAP)-induced platelet aggregation was 2.5-5 muM for human platelets and 0.25-0.5 muM for sheep platelets. PGAP was 4-5 times as potent versus human platelets as the olealdehyde and linolealdehyde acetal phosphatidic acids, which were equipotent.3 PGAP-induced irreversible aggregation of [(14)C]-5-hydroxytryptamine ([(14)C]-5-HT)-labelled human platelets in platelet-rich plasma was accompanied by release of 44.0+/-2.4% (s.e.) of the platelet [(14)C]-5-HT; reversible aggregation was not associated with release. In contrast, PGAP-induced release of [(14)C]-5-HT-labelled sheep platelets was dose-dependent.4 The adenosine diphosphate (ADP) antagonist, 2-methylthio-AMP, and the cyclo-oxygenase inhibitor, aspirin, abolished PGAP-induced second phase aggregation and release in human platelets but did not affect the first, reversible, phase of aggregation. Both the first and second phases of PGAP-induced aggregation were abolished by chlorpromazine, by the phospholipase A(2) inhibitor, mepacrine, and by nmolar concentrations of prostaglandin E(1) (PGE(1)); these agents abolished the second, but not the first phase of ADP-induced aggregation.5 The related phospholipids, lecithin, lysolecithin and phosphatidic acid, at <100 muM, neither induced aggregation of human platelets in platelet-rich plasma, nor modified PGAP-induced aggregation; 1-palmityl lysophosphatidic acid elicited aggregation of human platelets at a threshold concentration of 100 muM.6 It is concluded that the acetal phosphatidic acids induce platelet aggregation per se by direct action at the platelet membrane, and that the acetal function is of primary importance in their potent platelet-stimulating activity. Moreover, as the acetal phosphatidic acids are the major components of the smooth muscle-contracting acidic phospholipid tissue extract ;Darmstoff' (Vogt, 1949), their potent platelet-aggregating properties may be of physiological or pathological significance.


MutSβ regulates G4-associated telomeric R-loops to maintain telomere integrity in ALT cancer cells.
Up to 15% of human cancers maintain their telomeres through a telomerase-independent mechanism, termed "alternative lengthening of telomeres" (ALT) that relies on homologous recombination between telomeric sequences. Emerging evidence suggests that the recombinogenic nature of ALT telomeres results from the formation of RNA:DNA hybrids (R-loops) between telomeric DNA and the long-noncoding telomeric repeat-containing RNA (TERRA). Here, we show that the mismatch repair protein MutSβ, a heterodimer of MSH2 and MSH3 subunits, is enriched at telomeres in ALT cancer cells, where it prevents the accumulation of telomeric G-quadruplex (G4) structures and R-loops. Cells depleted of MSH3 display increased incidence of R-loop-dependent telomere fragility and accumulation of telomeric C-circles. We also demonstrate that purified MutSβ recognizes and destabilizes G4 structures in vitro. These data suggest that MutSβ destabilizes G4 structures in ALT telomeres to regulate TERRA R-loops, which is a prerequisite for maintenance of telomere integrity during ALT.


The pelvic digit: CT correlation and review of the literature.
Four additional cases of the developmental anomaly known variously as pelvic "ribs" or "digits" are presented with CT correlation in three cases. Comparison is made with the 12 cases reported in the literature, and their differential diagnosis is discussed.


Elective nodal irradiation versus involved-field irradiation for stage II-IV cervical esophageal squamous cell carcinoma patients undergoing definitive concurrent chemoradiotherapy: a retrospective propensity study with 8-year survival outcomes.
Definitive concurrent chemoradiotherapy (dCCRT) is suggested as the standard treatment for cervical esophageal squamous cell carcinoma (CESCC). This retrospective propensity study compared the 8-year survival outcomes and acute treatment toxicities of these patients treated with elective nodal irradiation (ENI) versus involved-field irradiation (IFI). Patients with stage II-IV CESCC treated with dCCRT at the Fourth Hospital of Hebei Medical University between January 1, 2007 and December 31, 2020 were enrolled in the study. All the patients were restaged according to the American Joint Commission 8th edition criteria. The propensity score matching (PSM) was used to minimize the effects of treatment selection bias and potential confounding factors including sex, age, ECOG score, clinical T stage, clinical N stage, clinical TNM stage and radiation dose between the ENI group and IFI group. Survival and the prognostic factors were evaluated. The 131 eligible patients underwent ENI (60 patients, 45.8%) or IFI (71 patients, 54.2%). The median follow-up time was 91.1 months (range, 23.8-182.0 months) for all the patients. The median OS, 1-, 3-, 5-, and 8-year OS rates were 44.4 months, 87.8%, 55.1%, 38.3%, and 27.2%, respectively. After PSM, there were 49 patients in each group. The median OS, 1-, 3-, 5-, and 8-year OS rates for ENI and IFI group were 32.0 months, 83.7%, 48.5%, 38.5% and 31.1% versus 45.2 months, 89.8%, 52.5%, 37.5%, 26.1%, respectively (P = 0.966; HR 0.99, 95% CI 0.61-1.61). Similar locoregional control was obtained in both groups. The tendency of leukocytopenia and neutropenia was higher in ENI than in IFI (59.2% vs. 38.8%; P = 0.068 and 30.6% vs. 14.3%; P = 0.089) at the end of dCCRT. Cervical esophageal squamous cell carcinoma patients undergoing definitive concurrent chemoradiotherapy has a satisfactory prognosis with organ conservation. The involved-field irradiation might be a better alternative owing to similar overall survival outcomes and local control with less toxicity of myelosuppression.


Effective gene transfer of lacZ and P0 into Schwann cells of P0-deficient mice.
Mutations in the gene encoding for the myelinating Schwann cell protein P0 have been linked to inherited peripheral neuropathies, including the Charcot-Marie-Tooth type 1B disease (CMT1B) and Dejerine-Sottas syndrome (DSS). Recently generated mice deficient in the P0 gene (P0-/- mice) resemble cases of CMT1B and DSS with impaired myelin dosage (Martini et al., 1995a). Potential approaches to treat such diseases include the introduction of the normal gene in the nerves of strongly affected patients. In the present study we used P0-/- mice to evaluate the efficiency of a replication-defective, E1-deleted adenovirus vector carrying the lacZ (Ad-RSV-lacZ) or P0 (Ad-RSV-P0) gene to infect abnormally myelinating Schwann cells. The Ad-RSV-lacZ vector suspension was injected into the left sciatic nerve ofPO-/- mice and the nerves examined for beta-galactosidase activity by X-gal histochemistry. Contralateral nerves injected with vehicle solution or non-injected served as controls. Beta-galactosidase activity was detected in nerves injected with the Ad-RSV-lacZ vector up to 2 weeks post-injection. Immunosuppressing the mice with FK506 to decrease the infiltration of activated T-cells in infected nerves lengthened beta-galactosidase activity to 8 weeks, the longest time point examined. Ultrastructural analysis indicated that X-gal crystals were present mostly in abnormally myelinating Schwann cells. These findings demonstrate that an adenovirus vector can successfully infect Schwann cells in P0-/- mice and expression can be maintained for several weeks. The Ad-RSV-P0 suspension was then injected in the sciatic nerve of immunosuppressed P0-/- mice. Two and four weeks post-injection both P0 mRNA and protein could be detected by in situ hybridization and Western blotting in some of the nerves. Furthermore, P0 protein expression was observed in myelin-like structures and onion bulb-like cells by immunohistochemistry. These results indicate that Schwann cells in P0-/- mice can be induced to produce P0 protein after gene transfer. Genetic repair of abnormal Schwann cells by using adenovirus vectors might be a possible technique to treat animal models of inherited peripheral neuropathies.


White matter hyperintensities and mild behavioral impairment: Findings from the MEMENTO cohort study.
White matter hyperintensities (WMH) contribute to cognitive decline and increase risk for dementia. Mild behavioral impairment (MBI) is a neurobehavioral syndrome characterized by the emergence and persistence of neuropsychiatric symptoms (NPS) in later life as an at-risk state for incident cognitive decline and dementia. Both WMH and MBI are common in patients with mild cognitive impairment (MCI), but few studies have established the link between these two risk markers in this population. Participants were memory clinic patients with MCI from the French MEMENTO study. WMH volume was quantified using brain magnetic resonance imaging. Participants were categorized into MBI+ and MBI- status based on NPS persistence, and the association between MBI status and domains with WMH volume was assessed with linear regression. A total of 768 participants [mean age 72.8 (SD=8.00); 57% female] were included. MBI (i.e., persistent NPS) was present in 229 participants (29.8%). MBI+ status was significantly associated with lower MMSE score and male sex. Compared to MBI-, MBI+ status was associated with 9.4% higher WMH volume [p = 0.01 (95% CI 2.0% to 16.7%)]. In this model, MMSE score was not associated with WMH volume. None of the MBI domains individually predicted greater WMH volume, although emotional dysregulation, impulse dyscontrol, and apathy trended towards significance. In a memory clinic sample of older adults with MCI, MBI was associated with higher WMH volume. Global MBI status outperformed MMSE and individual MBI domains, supporting the utility of MBI, a multi-NPS-domain composite assessment, for predicting WMH volume.


Variation in body composition of female big brown bats (Eptesicus fuscus) during lactation.
Most small mammals support the nutritional requirements of milk production by increasing food intake. However, when nutrient intake is low, maternal body reserves may be mobilized to maintain adequate milk output. We examined patterns of body composition, including dry matter, fat, protein, and mineral content in big brown bats, Eptesicus fuscus, during lactation. Concentrations of fat and phosphorus were markedly lower in lactating mothers during week three of lactation than during the first two weeks, but these constituents rebounded to previous levels in the fourth and fifth week. Rapid recovery from fat depletion suggests that females are able to adjust to changes in demands for energy. The decrease in phosphorus during mid-lactation suggests bone demineralization, but an interspecific comparison of adult concentrations of minerals prevalent in bone suggests that mineral concentrations may never reach critically low levels in reproductively active females.


Patients with multiple myeloma referred for palliative care consultation: from retrospective analysis to future directions to improve clinical outcomes.
New treatments have improved the overall survival of patients with multiple myeloma (MM). At diagnosis and during the course of the disease, patients often report pain and other symptoms. Given the long disease trajectory, psychological and social issues are also frequent. Recently, the potential usefulness of early palliative care (EPC) was hypothesized in the area of hematology. We conducted a retrospective analysis of patients with MM referred to our institute for a palliative care (PC) consultation between January 2017 and June 2020. Our aim was to evaluate the main reasons (pain or other clinical symptoms) for the referral for a first PC consultation. We examined the main reasons for the first PC consultation, the number of PC consultations carried out, and the period of time between diagnosis, first and subsequent PC visits, and death. We also recorded information on the type of pain experienced and the treatments administered. Of the 325 patients with MM followed at our hematology unit during the study period, 43 were referred for a PC consultation (39 for pain management and 4 to determine the most appropriate care setting (hospice or palliative homecare service)). Nineteen (44.2%) of the 43 patients reported other symptoms in addition to pain. The median time between MM diagnosis and the first PC consultation was 473 days. Fifteen patients died, with a median 332 days between the first PC visit and death. Randomized studies on MM involving larger patient populations with access to EPC are needed to identify an effective clinical model to improve the management of patients with MM.


Transurethral en bloc submucosal hydrodissection vs conventional resection for resection of non-muscle-invasive bladder cancer (HYBRIDBLUE): a randomised, multicentre trial.
To determine whether transurethral en bloc submucosal hydrodissection of bladder tumours (TUEB) improves the quality of the resection compared to conventional transurethral resection of bladder tumour (TURBT) in patients with non-muscle-invasive bladder cancer (NMIBC). A randomised, multicentre trial (HYBRIDBLUE) was conducted with a superiority design. Six German academic centres participated between September 2012 and August 2015. Based on literature analysis, a sample size for accurate histopathological assessment concerning muscle invasion was assumed to be feasible in 50% (P0 = 0.5) of TURBT and 80% of TUEB cases. After pre-screening of a total of 305 patients, participants were allocated to two study arms: Group I: hexaminolevulinate (HAL)-guided TUEB; Group II: conventional HAL-guided TURBT. The primary endpoint was the proportion of specimens that could be reliably evaluated pathologically concerning muscle invasiveness. Secondary endpoints included rates of histopathological completeness of the resection, muscularis propria content, recurrence, and complication rates. A total of 115 patients (TUEB 56; TURBT 59) were eligible for final analysis. Adequate histopathological assessment, which included muscularis propria content and tumour margins (R0 vs R1), was present in 48/56 (86%) TUEB patients compared to 37/59 (63%; P = 0.006) in the TURBT group. R0 was confirmed in 30/56 TUEB patients (57%) and five of 59 TURBT patients (9%; P < 0.001). No complications of Grade ≥III were observed in both arms. At 3 and 12 months, three and 19 patients recurred in the TUEB group vs seven and 11 patients in the TURBT group, respectively (P = 0.33 and P = 0.08). In this randomised study, TUEB was shown to be clinically safe regarding perioperative endpoints. An adequate histopathological assessment concerning muscle invasion was significantly better assessable in the TUEB arm compared to standard TURBT. This finding indicates the clinical potential for reducing the rate of early re-resections. Yet, a larger study with recurrence-free survival as the primary endpoint is needed to assess the oncological efficacy between both techniques.


Lipopolysaccharide induced anxiety- and depressive-like behaviour in mice are prevented by chronic pre-treatment of esculetin.
Inflammation and oxidative stress are involved in the pathophysiology of anxiety and depression. Esculetin (ESC), a coumarin derived potent antioxidant, also possessing anti-inflammatory and neuroprotective activity. This study investigated the effect of ESC in lipopolysaccharide (LPS)-induced anxiety- and depressive-like behaviour in mice. ESC (25 and 50mg/kg, p.o.) was administered daily for 14 days, and challenged with saline or LPS (0.83mg/kg; i.p.) on the 15th day. Behavioural paradigms such as elevated plus maze (EPM), open field test (OFT), forced swim test (FST) and tail suspension test (TST) were employed to assess anxiety- and depressive-like behaviour in mice post-LPS injection. Hippocampal cytokines, MDA and GSH level, and plasma corticosterone (CORT) were measured. ESC pre-treatment significantly (P<0.05) attenuated LPS-induced anxiety-like behaviour by modulating EPM and OFT parameters. Moreover, LPS-induced increase in immobility time in FST and TST were also prevented significantly (P<0.05) by ESC (50mg/kg). ESC pre-treatment ameliorated LPS-induced neuroinflammation by attenuating brain IL-1β, IL-6, TNF-α level, and oxidative stress as well as plasma CORT level. In conclusion, the results suggest that ESC prevented LPS-induced anxiety- and depressive-like behaviour which may be governed by inhibition of cytokine production, oxidative stress and plasma CORT level. The results support the potential usefulness of ESC in the treatment of psychiatric disorders associated with inflammation and oxidative stress.


Histological types of nasopharyngeal carcinoma in an intermediate risk area.
Between April and December 1974, 485 cases of NPC were seen at the Salah Azaïz Institute in Tunis. A histological study was carried out according to a classification that comprises four types of tumour:well-differentiated squamous-cell carcinoma, poorly-differentiated squamous-cell carcinoma, 'nasopharyngeal' type carcinoma and an anaplastic type. Some correlation between these histological types and clinical, epidemiological, virological and prognostic features was found.


Identification of genomic binding sites and direct target genes for the transcription factor DDIT3/CHOP.
DDIT3 is a tightly regulated basic leucine zipper (bZIP) transcription factor and key regulator in cellular stress responses. It is involved in a variety of pathological conditions and may cause cell cycle block and apoptosis. It is also implicated in differentiation of some specialized cell types and as an oncogene in several types of cancer. DDIT3 was originally believed to act as a dominant-negative inhibitor by forming heterodimers with other bZIP transcription factors, preventing their DNA binding and transactivating functions. DDIT3 has, however, been reported to bind DNA and regulate target genes. Here, we employed ChIP sequencing combined with microarray-based expression analysis to identify direct binding motifs and target genes of DDIT3. The results reveal DDIT3 binding to motifs similar to other bZIP transcription factors, known to form heterodimers with DDIT3. Binding to a class III satellite DNA repeat sequence was also detected. DDIT3 acted as a DNA-binding transcription factor and bound mainly to the promotor region of regulated genes. ChIP sequencing analysis of histone H3K27 methylation and acetylation showed a strong overlap between H3K27-acetylated marks and DDIT3 binding. These results support a role for DDIT3 as a transcriptional regulator of H3K27ac-marked genes in transcriptionally active chromatin.


4D Printing of shape-memory polymeric scaffolds for adaptive biomedical implantation.
4D printing has shown great potential in a variety of biomedical applications due to the adaptability and minimal invasiveness of fabricated devices. However, commonly employed shape memory polymers (SMPs) possess undesirable transition temperatures (Ttranss), leading to complications in implantation operations. Herein, we demonstrate 4D printing of a new SMP named poly(glycerol dodecanoate) acrylate (PGDA) with a Ttrans in a range of 20 °C - 37 °C making it appropriate for shape programming at room temperature and then shape deployment within the human body. In addition, the material possesses suitable rheological properties to allow for the fabrication of a variety of delicate 3D structures such as "triangular star", "six-petal flower", "honeycomb", "tube", tilted "truncated hollow cones", as well as overhanging "bridge", "cage", and "mesh". The printed 3D structures show shape memory properties including a large fixity ratio of 100% at 20 °C, a large recovery ratio of 98% at 37 °C, a stable cyclability of > 100 times, and a fast recovery speed of 0.4 s at 37 °C. Moreover, the Young's moduli of the printed structures can be decreased by 5 times due to the phase transition of PGDA, which is compatible with biological tissues. Finally, in vitro stenting and in vivo vascular grafting demonstrated the geometrical and mechanical adaptivity of the printed constructs for biomedical implantation. This newly developed PGDA SMP based 4D printing technology has the potential to pave a new route to the fabrication of shape memory scaffolds for personalized biomedical applications.


Periodic and nonperiodic burst responses of frog (Rana pipiens) retinal ganglion cells.
Neural activity of class 3 retinal ganglion cells was recorded in frog optic tectum, using extracellular microelectrodes. The stimuli were rectangular patches of contrast (light-on-dark or dark-on-light), applied within the previously determined receptive fields, for periods ranging from a few milliseconds to several seconds. ON and OFF responses were recorded for as long as 1 s following stimulation. Poststimulus time histograms revealed two types of responses, labeled periodic and nonperiodic bursters. The periodic bursters were characterized by periods of high activity separated by silent or near-silent intervals. The bursts occurred rhythmically with frequencies roughly between 15 and 50 Hz. Nonperiodic bursters generally showed both broad and sharp peaks in activity, but no regular periodicities. Activity profiles were flat initially, with silent periods appearing after the first few stimulus presentations, suggesting an inhibitory nature of the bursting process. The records were shown to combine the activities of several neurons. Analysis of the waveforms in real time made possible isolation of some units. In these cases, neurons exhibited a high degree of selective synchrony, i.e., the sharing of a portion of the activity profile, and notable differences at other times. These data have implications for the processing of visual information.


Polypharmacy and medication fill nonadherence in a population-based sample of adolescent and young adult cancer survivors, 2008-2017.
We examined the association between polypharmacy-an established risk factor for nonadherence in the elderly-and medication fill nonadherence in a large national sample of adolescent and young adult cancer survivors (AYAs) in the USA. We pooled data (2008-2017) from the Medical Expenditure Panel Survey. We defined polypharmacy as ≥ 3 unique medications prescribed, based on self-report and pharmacy data, and medication fill nonadherence as self-reported delay or inability to obtain a necessary medication. We estimated prevalence of medication fill nonadherence among AYAs (age 18-39 years with a cancer history). We used logistic regression to estimate the association between (1) polypharmacy and medication fill nonadherence in AYAs, and (2) total number of medications prescribed and medication fill nonadherence, controlling for sex, number of chronic conditions, disability, and survey year. AYAs (n = 598) were predominantly female (76.2%), age 30-39 years (64.9%), and non-Hispanic White (72.1%). Nearly half were poor (19.0%) or near-poor/low income (21.6%). One in ten AYAs reported medication fill nonadherence (9.75%). Of these, more than 70% cited cost-related barriers as the reason. AYAs with polypharmacy had 2.49 times higher odds of medication fill nonadherence (95%CI 1.11-5.59), compared to those without polypharmacy. Odds of medication fill nonadherence increased by 16% with each additional medication prescribed (AOR 1.16, 95% CI 1.07-1.25). Polypharmacy may be an important risk factor for medication fill nonadherence in AYAs in the USA. Improving AYAs' medication adherence requires eliminating cost-related barriers, particularly for those with polypharmacy.


A physiological correlate of disuse-induced sprouting at the neuromuscular junction.
Recent investigations have established that many of the normal properties of muscle fibres are maintained, at least in part, by muscle activity. Thus, a fall in resting membrane potential, an increase in input resistance, and spread of acetylcholine receptors to extrajunctional sites can all be induced by abolishing muscle activity and prevented by direct stimulation of denervated muscle fibres. Muscle activity also exerts a trophic influence on the innervating motoneurones; furthermore it may be a factor in the regulation of sprouting. Brown and Ironton found fine, "ultra-terminal sprouts" emanating from the endplates of muscles rendered inactive by chronic conduction block of the muscle nerve. Pestronk and Drachman saw increased branching of the motor nerve terminal and a consequent increase in endplate size in similar conditions. If these sprouts at the endplates of inactive muscles were functional, one might expect more transmitter to be released in response to nerve stimulation. We report here that both quantum content and spontaneous miniature endplate potential (m.e.p.p) frequency are increased at the terminals of inactive (disused) muscles.


Combination immunotherapy strategies for triple-negative breast cancer: current progress and barriers within the pharmacological landscape.
Triple-negative breast cancer (TNBC) is a breast cancer subtype characterized by poorer prognosis. Despite that TNBC can display immunogenic features, anti-PD(L)1 monotherapy strategies have resulted in disappointing results, underscoring the need to optimize their use in TNBC. Among many, combining immunotherapy with other agents to exploit the synergistic effect of different drugs has been explored. Such a combination approach led to the approval of immune checkpoint inhibitors (ICIs) plus chemotherapy in both metastatic and early setting. Nevertheless, primary or secondary resistance to ICIs remains a major hurdle to overcome, with a major need to explore novel combination strategies. This review summarizes the biological rationale, current evidence, and ongoing clinical trials of immunotherapy combined with novel immunotherapeutics, chemotherapy, targeted compounds, and antibody-drug conjugates. The treatment landscape of TNBC is in continuous changes. ICIs are now part of the clinical practice; however, several unmet needs still remain, including the need to overcome resistance and prolong benefit of ICIs. Exploiting synergism between different agent has emerged as an attractive strategy to extend the benefit obtained with ICIs. The goal of future research will be to unveil the mechanisms underlying resistance to ICIs and to identify better biomarkers for patient selection.


Uterine arterial blood flow and the substances of ovarian renin-angiotensin system in women with polycystic ovaries undergoing in vitro fertilization.
To find whether plasma and follicular prorenin concentrations have any effect on the uterine arterial blood flow in women with polycystic ovarian syndrome (PCOS) compared to those with normal menstrual cycles (NMC). Controlled prospective clinical study involved 55 women undergoing in vitro fertilization: 24 with PCOS and 31 with NMC. In both groups transvaginal colour Doppler assessment of uterine arterial blood flow was analysed on day 22 of the cycle, on the day of human chorionic gonadotrophin (HCG) administration and 36 h after HCG. Plasma and follicular (in the dominant follicle containing mature oocyte, and in the pooled follicles) prorenin and active renin, and serum estradiol and androstenedione concentrations were measured at these time-points. The Student's t-test and Pearson correlation were used for the statistical analysis. The resistance index (RI) in the NMC group decreased from 0.84+/-0.05 on the day of HCG to 0.78+/-0.08 36 h after HCG (P < 0.05); in the PCOS group the RI did not decrease. Follicular prorenin concentrations in the dominant follicle and in the pooled follicles were lower in the PCOS than in the NMC group (20,210+/-10,831 microU/l, 16,753+/-8634 microU/l versus 42,637+/-35,400 microU/l, 33,067+/-26,200 microU/l; P < 0.05). Plasma prorenin concentrations do not affect vascular impedance to the uterine artery, but follicular prorenin do by newly formed low resistant vessels in the follicles.


Promoter variants of KIR2DL5 add to diversity and may impact gene expression.
Sequencing of polymerase chain reaction (PCR)-amplified genomic DNA encompassing the putative proximal promoter and the coding region was used to identify KIR2DL5 alleles from 77 unrelated Caucasian individuals. PCR and sequencing were used to link each new allele to its neighboring KIR locus to identify 2DL5A or 2DL5B loci. Allele 2DL5A*001 was found in 24 of the 37 2DL5 positive individuals; 2DL5B*0020101 and 2DL5A*0050101 were also observed. Two new alleles, 2DL5B*008 and 2DL5B*009, contained substitutions altering the amino acid sequence of the leader and transmembrane region, respectively. Two other novel alleles, 2DL5B*0020102 and 2DL5A*0050102, contained alterations of the 5' upstream region, bringing the number of unique promoter sequences to six. Promoter activity of the alleles was compared using luciferase reporter assays. Our results support those recently published, in which the promoter of 2DL5B*0020101 was shown to be more active in vitro compared to 2DL5A*001, and also provide additional information about the transcriptional activity of the promoters of the newly characterized alleles related to two altered transcription factor binding sites.


Identification of nuclear envelope proteins and glycoproteins which co-isolate with the nuclear protein matrix.
Nuclear envelopes and nuclear matrices were isolated from rat liver nuclei. Although differences in polypeptide composition of the structures are evident on SDS gel electrophoresis, they have an almost identical distribution of concanavalin A-binding glycoproteins. These matrix-associated concanavalin A-binding glycoproteins derive entirely from the nuclear envelope and are recovered almost quantitatively in the matrix. They constitute easily identifiable markers for nuclear envelope association with matrix or other nuclear subfractions. Surface labelling of nuclei with 125I using solid-phase lactoperoxidase further confirmed that a large number of envelope-associated nuclear surface proteins co-isolate with the matrix. Protein kinase activity, as well as endogenous substrates for the kinase(s) are shown to be the same in both envelopes and matrix. Envelope-derived proteins and glycoproteins may comprise a substantial proportion of total matrix protein.


Self-organization and neuronal avalanches in networks of dissociated cortical neurons.
Dissociated cortical neurons from rat embryos cultured onto micro-electrode arrays exhibit characteristic patterns of electrophysiological activity, ranging from isolated spikes in the first days of development to highly synchronized bursts after 3-4 weeks in vitro. In this work we analyzed these features by considering the approach proposed by the self-organized criticality theory: we found that networks of dissociated cortical neurons also generate spontaneous events of spreading activity, previously observed in cortical slices, in the form of neuronal avalanches. Choosing an appropriate time scale of observation to detect such neuronal avalanches, we studied the dynamics by considering the spontaneous activity during acute recordings in mature cultures and following the development of the network. We observed different behaviors, i.e. sub-critical, critical or super-critical distributions of avalanche sizes and durations, depending on both the age and the development of cultures. In order to clarify this variability, neuronal avalanches were correlated with other statistical parameters describing the global activity of the network. Criticality was found in correspondence to medium synchronization among bursts and high ratio between bursting and spiking activity. Then, the action of specific drugs affecting global bursting dynamics (i.e. acetylcholine and bicuculline) was investigated to confirm the correlation between criticality and regulated balance between synchronization and variability in the bursting activity. Finally, a computational model of neuronal network was developed in order to interpret the experimental results and understand which parameters (e.g. connectivity, excitability) influence the distribution of avalanches. In summary, cortical neurons preserve their capability to self-organize in an effective network even when dissociated and cultured in vitro. The distribution of avalanche features seems to be critical in those cultures displaying medium synchronization among bursts and poor random spiking activity, as confirmed by chemical manipulation experiments and modeling studies.


Transcriptome-wide association study-derived genes as potential visceral adipose tissue-specific targets for type 2 diabetes.
This study aimed to assess the causal relationship between visceral obesity and type 2 diabetes and subsequently to screen visceral adipose tissue (VAT)-specific targets for type 2 diabetes. We examined the causal relationship between VAT and type 2 diabetes using bidirectional Mendelian randomisation (MR) followed by multivariable MR. We conducted a transcriptome-wide association study (TWAS) leveraging prediction models and a large-scale type 2 diabetes genome-wide association study (74,124 cases and 824,006 controls) to identify candidate genes in VAT and used summary-data-based MR (SMR) and co-localisation analysis to map causal genes. We performed enrichment and single-cell RNA-seq analyses to determine the cell-specific localisation of the TWAS-identified genes. We also conducted knockdown experiments in 3T3-L1 pre-adipocytes. MR analyses showed a causal relationship between genetically increased VAT mass and type 2 diabetes (inverse-variance weighted OR 2.48 [95% CI 2.21, 2.79]). Ten VAT-specific candidate genes were associated with type 2 diabetes after Bonferroni correction, including five causal genes supported by SMR and co-localisation: PABPC4 (1p34.3); CCNE2 (8q22.1); HAUS6 (9p22.1); CWF19L1 (10q24.31); and CCDC92 (12q24.31). Combined with enrichment analyses, clarifying cell-type specificity with single-cell RNA-seq data indicated that most TWAS-identified candidate genes appear more likely to be associated with adipocytes in VAT. Knockdown experiments suggested that Pabpc4 likely contributes to regulating differentiation and energy metabolism in 3T3-L1 adipocytes. Our findings provide new insights into the genetic basis and biological processes of the association between VAT accumulation and type 2 diabetes and warrant investigation through further functional studies to validate these VAT-specific candidate genes.


The roles of group membership and social exclusion in children's testimonial learning.
Here, we used high- and low-stakes testimonial learning tasks to better understand two important types of social influence on children's learning decisions: group membership and social ostracism. Children (4- and 5-year-olds; N = 100) were either included or excluded by in-group or outgroup members in an online ball tossing game. Then, children were asked to selectively learn new information from either an in-group or out-group member. They also received counterintuitive information from an in-group or out-group member that was in conflict with their own intuitions. When learning new information, children who were excluded were more likely to selectively trust information from their in-group member. In contrast, when accepting counterintuitive information, children relied only on group membership regardless of their exclusion status. Together, these findings demonstrate ways in which different forms of testimonial learning are guided not only by epistemic motivations but also by social motivations of affiliation and maintaining relationships with others.


Inhibition of macrophage- and neutrophil-mediated cytotoxicity by verapamil.
Peripheral blood monocyte-derived macrophages and polymorphonuclear leukocytes (PMNs) obtained from normal donors kill tumor cells in vitro. However, if verapamil is added to the macrophages or neutrophil tumor cell suspensions in microgram concentrations (0.1 microgram to 0.1 mg), there is marked inhibition of tumor cell killing. The inhibitory effect for the macrophages resulted from an effect of verapamil on both the effector and target cells. When either the effector cells or target cells were preincubated with verapamil, they became resistant to the effects of the cytotoxic macrophages. Cytotoxicity was also inhibited when 0.1 mg of verapamil was added to the macrophages monolayers either at the time of addition of the tumor cells or 15-30 min after addition of the tumor cells, whereas no inhibition of cytotoxicity occurred when verapamil was added more than 30 min after the initiation of the cytotoxic reaction. For the neutrophils it was observed that the inhibitory activity resulted from an effect of verapamil on the effector cells rather than the target cells. When the effector cells were preincubated with verapamil they became incapable of killing the tumor cells, whereas preincubation of the target cells with verapamil had no effect on their ability to be killed by the neutrophils. Cytotoxicity was also inhibited when 0.1 mg of verapamil was added to the neutrophil monolayers either at the time of addition of the tumor cells or 15-60 min after addition of the tumor cells, whereas no inhibition of cytotoxicity occurred when verapamil was added more than 60 min after the initiation of the cytotoxic reaction.


The influence of peri-operative depressive symptoms on medium-term spine surgery outcome: a prospective study.
To investigate the role of depressive symptoms on clinical outcomes in patients undergoing spinal surgery up to 2-year follow-up. The study used data from an institutional spine surgery registry (January 2016, through March 2022) to identify patients (> 18 years) undergoing spine surgery. Patients with Oswestry Disability Index (ODI) < 20/100 at baseline or undergoing surgery on the cervical spine or for idiopathic spinal deformity and trauma patients were excluded. The patients were divided into two groups based on the pre-operative Mental Component Summary (MCS) score of the SF-36: depression group (MCS ≤ 35) or non-depression group (MCS > 35). The ODI and MCS scores trajectory were wined over the 24-month post-surgery between groups. Additionally, a secondary subgroup analysis was conducted comparing outcomes between those with depressive symptoms (persistent-depression subgroup) and those without depressive symptoms (never-depression subgroup) at 3 months after surgery. A total of 2164 patients who underwent spine surgery were included. The pre-operative depression group reported higher ODI total scores and lower MCS than the pre-operative non-depression group at all time points (P < 0.001). The persistent-depression subgroup reported higher ODI total scores and lower MCS than the never-depression subgroup at all follow-ups (P < 0.001). Functional disability and mental health status improve in patients with depression symptoms undergoing spinal surgery. Despite this improvement, they do not reach the values of non-depressed subjects. Over the 2-year follow-up time, patients with depression show a different trajectory of ODI and MCS. Caregivers should be aware of these results to counsel patients with depression symptoms.


Stereologic and ultrastructural comparison of human and rat amniotic membrane wrapping for rat sciatic nerve repair.
In this study we aimed to examine the effects on wound healing and nerve regeneration of human and rat amniotic membrane wraps around primary epineural anastomosis areas after a peripheral nerve transection injury in rats. We randomized 25 male adult rats with induced peripheral transection injuries into 5 groups (control, transection injury, primary epineural anastomosis [PEA] after injury, PEA with a human amniotic membrane [hAM] wrap, and PEA with a rat amniotic membrane [rAM] wrap groups and treated their injuries accordingly. We took tissue samples from the anastomosis regions, 12 weeks after the experiment, and analyzed them stereologically and ultrastructurally. We performed a statistical analysis with the recovered stereological counts and the measurement data. Our results showed that the use of amniotic membranes for allografts (between same species) instead of xenografts (between different species), along with microsurgery, provides a suitable microenvironment during the healing process with less immunological reaction on the injured site and supports axonal regeneration.


[Effect of furosemide on the amino acid content of serum and elimination by the kidneys].
The effect of intraventously administered furosemide (20 mg) on the concentration of 21 amino acids in the blood serum and urine of 6 healthy volunteers was investigated. A substantially increased concentration of glutaminic acid and citrulline and a statistically significantly greater excretion of arginine with urine were ascretained.


Development, Characterization, Optimization, and In Vivo Evaluation of Methacrylic Acid-Ethyl Acrylate Copolymer Nanoparticles Loaded with Glibenclamide in Diabetic Rats for Oral Administration.
The methacrylic acid-ethyl acrylate copolymer nanoparticles were prepared using the solvent displacement method. The independent variables were the drug/polymer ratio, surfactant concentration, Polioxyl 40 hydrogenated castor oil, the added water volume, time, and stirring speed, while size, PDI, zeta potential, and encapsulation efficiency were the response variables analyzed. A design of screening experiments was carried out to subsequently perform the optimization of the nanoparticle preparation process. The optimal formulation was characterized through the dependent variables size, PDI, zeta potential, encapsulation efficiency and drug release profiles. In vivo tests were performed in Wistar rats previously induced with diabetes by administration of streptozotocin. Once hyperglycemia was determined in rats, a suspension of nanoparticles loaded with glibenclamide was administered to them while the other group was administered with tablets of glibenclamide. The optimal nanoparticle formulation obtained a size of 18.98 +/- 9.14 nm with a PDI of 0.37085 +/- 0.014 and a zeta potential of -13.7125 +/- 1.82 mV; the encapsulation efficiency was of 44.5%. The in vivo model demonstrated a significant effect (p < 0.05) between the group administered with nanoparticles loaded with glibenclamide and the group administered with tablets compared to the group of untreated individuals.


Six-Year Surveillance of Acquired Bloodstream Infection in a Pediatric Intensive Care Unit in Israel.
We studied profile of the bloodstream infections (BSI) in the pediatric intensive care unit (PICU) and identified predictors of mortality. The study collected data from hospital records for children younger than 18-years who developed BSI during their PICU stay between 2014 and 2019. In 114 patients, 136 PICU-acquired BSIs with 152 pathogens were documented. The incidence of BSI was 47.12/1,000 PICU admissions and 7.95/1000 PICU hospital days. Gram-negative rods accounted for 75% of isolates, Gram-positive cocci accounted for 21.7% of isolates, and fungi accounted for 3.3% of isolated pathogens. ICU mortality was observed in 25 (21.9%) patients with a BSI compared to 94 (3.1%) patients without a BSI (P<0.001). Hemodynamic instability (P=0.014, OR 4.10, CI 1.33-12.66), higher blood urea nitrogen (BUN) (P=0.044), and lower albumin levels (P=0.029) were associated with increased risk of ICU mortality. BSI in the PICU is associated with increased mortality. Early identification and management of risk factors independently associated with poor clinical outcomes in these patients should be aimed to ensure improved survival.


Impact of obesity on early erectile function recovery after robotic radical prostatectomy.
Studies are limited regarding the impact of obesity on early erectile functional outcomes after robotic radical prostatectomy. Our goal was to determine this impact using patient-reported validated questionnaires. International Index of Erectile Function (IIEF-6) scores were prospectively collected with institutional review board approval, for patients who underwent robotic radical prostatectomy with bilateral nerve sparing from February 2007 to October 2009. The data were categorized into nonobese and obese groups and subsequently into 2 subgroups based on risk for postprostatectomy erectile dysfunction. Low risk is preoperative IIEF-6 ≥19 and high risk is IIEF-6 <19. The groups and subgroups were compared using chi-square analysis. Of 190 consecutive patients, 67 were excluded for preoperative severe erectile dysfunction (IIEF-6<7), or lack of IIEF-6 scores, or both. There were 69 nonobese patients of which 88% were potent preoperatively and 20% regained potency at 12 months postoperatively. Of 54 obese patients, 85% were potent preoperatively and 25% at 12 months. There was no difference in erectile function recovery rates between the groups (P=0.755). In both groups, patients with low risk of postoperative erectile dysfunction had statistically similar postoperative mean IIEF-6 scores at 6 and 12 months (P=0.580 and P=0.389, respectively), and no difference in erectile function recovery rates existed at 12 months (P=0.735). Obesity has no major contribution to the rate of early erectile function recovery after robotic radical prostatectomy. Preoperative erectile function remains the determining factor in postradical prostatectomy erectile dysfunction.


Multi-molecular markers and metals as tracers of organic matter inputs and contamination status from an Environmental Protection Area in the SW Atlantic (Laranjeiras Bay, Brazil).
The sources and concentrations of aliphatic hydrocarbons (AHs) and polycyclic aromatic hydrocarbons (PAHs), faecal and biogenic sterols, and trace metals at 10 sampling sites located in Laranjeiras Bay, a large Environmental Protection Area in the southern Atlantic region of Brazil, were determined to assess the sources of organic matter and the contamination status of estuarine sediments. Organic compounds were determined by GC-FID and GC-MS, and ICP-OES was used to evaluate trace metals. The total AHs concentration ranged from 0.28 to 8.19 μg g(-1), and n-C(29) and n-C(31) alkanes were predominant, indicating significant inputs from higher terrestrial plants. Unresolved complex mixtures (UCM) were not detected at any site, suggesting that the study area was not significantly contaminated by fossil fuels. The total PAH concentration varied from 3.85 to 89.2 ng g(-1). The ratio between selected PAH isomers showed that combustion of biomass, coal, and petroleum is the main source of PAHs in the study area. The concentrations of the faecal sterols coprostanol and epicoprostanol were below the detection limits, suggesting that sewage was not a significant contributor to sedimentary organic matter. The concentrations of the trace metals (As, Cr, Cu, Ni, Pb and Zn) were low, except near sites located at the mouths of rivers that discharge into the study area and near urbanised regions (Paranaguá city and the adjoining harbour). In general, the concentrations of PAHs were below the threshold effect concentrations (TEL) levels. Although the As, Cr and Ni concentrations were above the TEL levels, the study area can be considered as preserved from human activities.


Detailed presurgical evaluation of a case of congenital bladder diverticulum.
Congenital bladder diverticulum is rare and is usually observed in male children. An 8-year-old Japanese boy was referred to a hospital with fever and gross hematuria and was treated with a course of antibiotics. Because the dilatation of the ureter was suspected by abdominal ultrasonographic examination, he was referred to our hospital. We diagnosed congenital bladder diverticulum by computed tomographic scan and carried out laparoscopic bladder diverticulectomy and extravesical ureteral reimplantation. Four years later, there was no recurrence of gross hematuria or urinary tract infection.


[Chalazion or basalioma in an oil painting of the National Portraits Gallery in London].
Using an oil painting by G.F. Watts displayed in the National Portrait Gallery of London, we made an attempt to diagnose the dermatological alterations recognizable.


Enhancement of 3D Bi2MoO6 mesoporous spheres photocatalytic performance by vacancy engineering.
The three-dimensional Bi2MoO6 mesoporous architectures constructed by nanosheets were synthesized through solvothermal method. The photocatalytic efficiency for tetracycline (TC) by the pristine Bi2MO6 and the BMO-450 (pristine Bi2MO6 was calcined at 450 °C) reached 73% and 90% after 150 min light irradiation, respectively. Compared to the photocatalytic efficiency of pristine Bi2MoO6, the BMO-450 exhibited much higher photocatalytic performance owing to the presence of oxygen vacancies obvious change the band structure of BMO-450. The X-ray photoelectron spectroscopy (XPS) revealed that the presence of oxygen vacancy in the BMO-450 crystal, which endowed it outstanding photocatalytic performance. Moreover, the BMO-450 possess high crystallization degree, mesoporous structure and the decreasing band gap. The excellent photocatalytic performance for the degradation of TC aqueous solutions, which demonstrate that the calcined Bi2MoO6 mesoporous spheres would have potential applications in the fields of treating wastewater.


Microstructures, Mechanical Properties, and Corrosion Behavior of As-Cast Mg⁻2.0Zn⁻0.5Zr⁻xGd (wt %) Biodegradable Alloys.
The Mg⁻Zn⁻Zr⁻Gd alloys belong to a group of biometallic alloys suitable for bone substitution. While biocompatibility arises from the harmlessness of the metals, the biocorrosion behavior and its origins remain elusive. Here, aiming for the tailored biodegradability, we prepared the Mg⁻2.0Zn⁻0.5Zr⁻xGd (wt %) alloys with different Gd percentages (x = 0, 1, 2, 3, 4, 5), and studied their microstructures and biocorrosion behavior. Results showed that adding a moderate amount of Gd into Mg⁻2.0Zn⁻0.5Zr alloys will refine and homogenize α-Mg grains, change the morphology and distribution of (Mg, Zn)₃Gd, and lead to enhancement of mechanical properties and anticorrosive performance. At the optimized content of 3.0%, the fishbone-shaped network, ellipsoidal, and rod-like (Mg, Zn)₃Gd phase turns up, along with the 14H-type long period stacking ordered (14H-LPSO) structures decorated with nanoscale rod-like (Mg, Zn)₃Gd phases. The 14H-LPSO structure only exists when x ≥ 3.0, and its content increases with the Gd content. The Mg⁻2.0Zn⁻0.5Zr⁻3.0Gd alloy possesses a better ultimate tensile strength of 204 ± 3 MPa, yield strength of 155 ± 3 MPa, and elongation of 10.6 ± 0.6%. Corrosion tests verified that the Mg⁻2.0Zn⁻0.5Zr⁻3.0Gd alloy possesses the best corrosion resistance and uniform corrosion mode. The microstructure impacts on the corrosion resistance were also studied.


Brain Features of Treatment-Resistant Depression: A Review of Structural and Functional Connectivity Magnetic Resonance Imaging Studies.
Increased awareness of the growing disease burden of treatment resistant depression (TRD), in combination with technological advances in MRI, affords the unique opportunity to research biomarkers that characterize TRD. We provide a narrative review of MRI studies investigating brain features associated with treatment-resistance and treatment outcome in those with TRD. Despite heterogeneity in methods and outcomes, relatively consistent findings include reduced gray matter volume in cortical regions and reduced white matter structural integrity in those with TRD. Alterations in resting state functional connectivity of the default mode network were also found. Larger studies with prospective designs are warranted.


Technique for assessing visual discrimination learning in mice.
An automated technique for the study of visual discrimination learning in mice has been developed. The technique utilizes a nose-poke as the operant response. The nose-poke response requires no shaping, has a relatively high operant level and can be used to measure preacquisition exploratory behavior. CD-1 mice acquired a simultaneous brightness discrimination readily but a successive brightness discrimination proved more difficult. A 20 sec intertrial interval was optimal for acquisition of the simultaneous discrimination. Reversal learning was slow. This procedure should prove useful in the study of the effects of pharmacologic and toxic agents on learning and performance in both weanlings and adult mice.


European college of orthodontics: commission of affiliation and titularisation.
Date of birth: 28/4/1977; sex: female. A. (4/2006; 29 years). Tooth-arch discrepancy with bi-maxillary protrusion. Correction of bi-maxillary protrusion; avulsion of 15, 25, 35 and 45; fixed multi-bracket Incognito bi-maxillary appliance; mini-screw anchorage. B. POST-TREATMENT RECORDS DOCUMENTS: (9/2009; 32 years and 6 months). Permanent retainers using fixed upper and lower bonded wires. C. POST-RETENTION RECORDS: (7/2010; 33 years and 3 months). D. Reason for consultation: correction of crooked and "jutting" teeth. Extraoral examination: balanced facial levels; lateral view: predominant lower third; closed nasolabial angle; labial asymmetry with predominant lower lips. Endooral examination: young adult dentition; average dental status; large number of fillings; panorex confirms four devitalized teeth; good periodontal status; V-shaped upper arch with lingually ectopic 12 and 22; lower arch with slight incisor crowding; bi-lateral molar and canine Class I; crossbite of 12 and 22; 2-mm deepbite and 1-mm overjet.


Anterograde transport of HSV-1 and HSV-2 in the visual system.
The anterograde spread of herpesvirus in the visual system subsequent to retinitis has been observed clinically. We compared the ability of two well-studied Herpes simplex virus (HSV) strains to be transported in the anterograde direction in the hamster visual system: strain McIntyre, representing HSV-1, and strain 186, representing HSV-2. Intravitreal injection of HSV-2 labeled more retinorecipient neurons than did HSV-1, suggesting important type differences in the ability of HSV to infect retinorecipient neurons after intravitreal injection. The most likely explanation for our results is that HSV-2 is more efficiently adsorbed than HSV-1 in the retinal ganglion cells. Our results also suggest that HSV may be useful as an anterograde transneuronal tracer for neuroanatomical studies of the visual system.


A movable gestational sac in association with a myometrial defect.
An ultrasound examination in a woman at 9 weeks' gestation demonstrated a gestational sac with a live fetus in the left uterine horn which was surrounded by an extremely thin outer lining. An interstitial pregnancy was suspected and laparoscopy was performed. During laparoscopy the purple bulge in the left horn gradually reduced in size and eventually disappeared following the external pressure by the tip of the forceps. We believe this pressure caused contraction of the superficial myometrial fibers resulting in a shift in the location of the gestational sac to the central area of the uterus. The pregnancy continued and on Cesarean section at 34 weeks' gestation, a membranous protrusion of the uterine wall in the left horn was noticed. A myometrial defect caused by an intrauterine intervention in the patient's previous pregnancy was suspected to be the cause of this "movable gestational sac" phenomenon.


Fatty acid binding protein 1 and fatty acid synthetase over-expression have differential effects on collagen III synthesis and cross-linking in Zongdihua pig primary adipocytes.
The purpose of this study was to determine whether FABP1 and FAS regulate expression of collagen and its crosslinking via lysyl oxidase in isolated adipocytes from Zongdihua pigs. We aimed to identify biochemical processes affecting meat quality using molecular tools to provide a basis for breeding improvement of these animals. We measured expression levels of FABP1 and related genes using qRT-PCR in longissimus dorsi muscle and subcutaneous adipose tissues. Primary adipocytes from fat tissues were isolated and FABP1 and FAS were over-expressed from recombinant plasmids. Sequence analysis of the cloned genes indicated that FABP1 encodes a hydrophobic protein of 128 amino acids and contained 12 predicted phosphorylation sites and no transmembrane regions. The basal levels of FABP1 and FAS expression in pig tissues were 3-3.5-fold higher in subcutaneous fat compared with muscle (P < 0.01). Recombinant expression plasmids were successfully transfected into the cloned preadipocytes and (a) over-expression of FAS resulted in significantly increased expression of COL3A1 (P < 0.05) and significantly inhibited lysyl oxidase LOX expression (P < 0.01); (b) over-expression of FABP1 significantly increased COL3A1 expression (P < 0.01) and significantly inhibited LOX expression (P< 0.05) and significantly reduced lysyl oxidase activity (P < 0.01). Therefore, FAS enhanced FABP1 expression resulting in increased collagen accumulation and this preliminarily suggested that FAS and FABP1 can serve as fat-related candidate genes and provide a theoretical basis for the study of fat deposition in Zongdihua pigs.


An in vivo drug repurposing screen and transcriptional analyses reveals the serotonin pathway and GSK3 as major therapeutic targets for NGLY1 deficiency.
NGLY1 deficiency, a rare disease with no effective treatment, is caused by autosomal recessive, loss-of-function mutations in the N-glycanase 1 (NGLY1) gene and is characterized by global developmental delay, hypotonia, alacrima, and seizures. We used a Drosophila model of NGLY1 deficiency to conduct an in vivo, unbiased, small molecule, repurposing screen of FDA-approved drugs to identify therapeutic compounds. Seventeen molecules partially rescued lethality in a patient-specific NGLY1 deficiency model, including multiple serotonin and dopamine modulators. Exclusive dNGLY1 expression in serotonin and dopamine neurons, in an otherwise dNGLY1 deficient fly, was sufficient to partially rescue lethality. Further, genetic modifier and transcriptomic data supports the importance of serotonin signaling in NGLY1 deficiency. Connectivity Map analysis identified glycogen synthase kinase 3 (GSK3) inhibition as a potential therapeutic mechanism for NGLY1 deficiency, which we experimentally validated with TWS119, lithium, and GSK3 knockdown. Strikingly, GSK3 inhibitors and a serotonin modulator rescued size defects in dNGLY1 deficient larvae upon proteasome inhibition, suggesting that these compounds act through NRF1, a transcription factor that is regulated by NGLY1 and regulates proteasome expression. This study reveals the importance of the serotonin pathway in NGLY1 deficiency, and serotonin modulators or GSK3 inhibitors may be effective therapeutics for this rare disease.


Automatic detection and segmentation of chorda tympani under microscopic vision in otosclerosis patients via convolutional neural networks.
Artificial intelligence (AI) techniques, especially deep learning (DL) techniques, have shown promising results for various computer vision tasks in the field of surgery. However, AI-guided navigation during microscopic surgery for real-time surgical guidance and decision support is much more complex, and its efficacy has yet to be demonstrated. We propose a model dedicated to the evaluation of DL-based semantic segmentation of chorda tympani (CT) during microscopic surgery. Various convolutional neural networks were constructed, trained, and validated for semantic segmentation of CT. Our dataset has 5817 images annotated from 36 patients, which were further randomly split into the training set (90%, 5236 images) and validation set (10%, 581 images). In addition, 1500 raw images from 3 patients (500 images randomly selected per patient) were used to evaluate the network performance. When evaluated on a validation set (581 images), our proposed CT detection networks achieved great performance, and the modified U-net performed best (mIOU = 0.892, mPA = 0.9427). Moreover, when applying U-net to predict the test set (1500 raw images from 3 patients), our methods also showed great overall performance (Accuracy = 0.976, Precision = 0.996, Sensitivity = 0.979, Specificity = 0.902). This study suggests that DL can be used for the automated detection and segmentation of CT in patients with otosclerosis during microscopic surgery with a high degree of performance. Our research validated the potential feasibility for future vision-based navigation surgical assistance and autonomous surgery using AI.


Methoctramine and hexahydrodifenidol antagonise two muscarinic responses on the rat superior cervical ganglion with opposite selectivity.
Two novel muscarinic antagonists, methoctramine and hexahydrodifenidol, have been assessed for their action against two muscarinic agonist-induced responses on the rat superior cervical ganglion in vitro. DC recordings were made between the desheathed ganglion and its internal carotid nerve using the grease-gap technique. Hexahydrodifenidol and methoctramine antagonised the muscarine-induced M1-mediated depolarisation of this preparation with estimated pA2 values of 7.5 and 6.5, respectively. In 0.3 microM pirenzepine and 0.1 mM CaCl2, 1 microM muscarine evoked a hyperpolarisation mediated by cardiac-like M2 receptors. Hexahydrodifenidol and methoctramine antagonised this response with pIC50 values (-log10IC50) of 5.7 and 7.4, respectively. The selectivity of methoctramine for cardiac-like M2 receptors over M1 receptors is therefore confirmed and extended to these two neuronal responses. The selectivity of hexahydrodifenidol was opposite to, and greater than, that seen with methoctramine.


A rare case report of rib hemangioma mimicking a malignant bone tumor or metastatic tumor.
Hemangioma of the rib is a rare benign vascular tumor. This benign disease induces osteolytic changes, and must be distinguished from a malignant bone tumor or metastatic tumor. Definitive diagnosis is achieved by excision biopsy or histological examination after surgical resection in many cases. We here in present a rare case of hemangioma of the rib.


Exploring young adults' contraceptive knowledge and attitudes: disparities by race/ethnicity and age.
Half of pregnancies in the United States are unintended, with the highest proportions occurring among Blacks, Hispanics, and teenagers. Understanding differences in knowledge and attitudes about contraception by race/ethnicity and age can improve efforts to reduce disparities in unintended pregnancy. This analysis used data from the 897 female respondents in National Survey of Reproductive and Contraceptive Knowledge, a survey exploring young adults' knowledge and attitudes about contraception and pregnancy. Bivariate and multivariate logistic regression analyses were used to assess racial/ethnic and age group differences in knowledge and attitudes about contraceptives. Hispanics and teenagers (aged 18-19) had lower awareness of available contraceptive methods, and lower knowledge about individual methods compared with White women and young adults (age 20-29). For example, Hispanics (74%) and teenagers (77%) were less likely to have heard of the intrauterine device (IUD) than were White women (90%) and young adults (90%), and were less likely to know that a woman experiencing side effects could switch brands of oral contraceptive pills (72% of Hispanics vs. 86% of White women; 76% of teenagers vs. 90% of young adults). Hispanics born outside the United States had lower knowledge about contraceptives than U.S.-born Hispanics. For example, foreign-born Hispanics were less likely than U.S.-born Hispanics to have heard of the IUD (59% vs. 82%) or the vaginal ring (55% vs. 95%). Lower contraceptive knowledge among teenagers and Hispanics, particularly immigrants, suggests the importance of disseminating family planning information to these women as one means to address disparities in unintended pregnancy.


Local health department 2009 H1N1 influenza vaccination clinics-CDC staffing model comparison and other best practices.
Mass vaccination clinic staffing models, such as the Centers for Disease Control and Prevention Large-Scale Vaccination Clinic Output and Staff Estimates: An Example, provide guidance on appropriate roles and number of staff for successful mass vaccination clinics within local and state health departments. The Kent County Health Department used this model as a starting point for mass vaccination clinics in response to 2009 H1N1 influenza. In addition to discussion of successful modification of the Centers for Disease Control and Prevention model to maximize local health department mass vaccination clinic efficiency, additional best practices including use of the Incident Command System and a reservation system are provided. Use of the provided modified staffing model and additional best practices will increase the success of health department mass vaccination clinics, and should be considered not only for future public health emergencies, but also for seasonal influenza vaccination campaigns.


Atrioventricular and ventriculo-atrial conduction in patients with symptomatic sinus node dysfunction.
In 14 patients with symptomatic sinus node dysfunction--sinus bradycardia, sino-atrial exit block, or sinus arrest--electrophysiological studies were performed before implantation of a pacemaker. In 8 patients incremental high right atrial pacing showed AV-nodal Wenckebach at pacing rates equal to or above 130/min (group I); in 6 patients AV-nodal Wenckebach was reached at pacing rates less than 130/min (group II). During ventricular pacing at a rate 10-15% faster than the existing sinus rate, ventriculo-atrial (VA) conduction was present in all patients of group I, while VA conduction was present in only 2 patients of group II (p less than 0.05). Patients with symptomatic sinus node dysfunction but with intact AV conduction frequently show VA conduction during ventricular pacing and thus are particularly at risk for developing a pacemaker syndrome when a ventricular demand (VVI) pacemaker is implanted. This complication can be avoided by atrial demand (AAI) pacing or AV sequential (DVI) pacing. When adequate experience has been gathered with AV universal (DDD) pacemakers, the indications for selection of a pacemaker in patients with symptomatic sinus node dysfunction will probably change.


Mechanisms of ranolazine pretreatment in preventing ventricular tachyarrhythmias in diabetic db/db mice with acute regional ischemia-reperfusion injury.
Studies have demonstrated that diabetic (db/db) mice have increased susceptibility to myocardial ischemia-reperfusion (IR) injury and ventricular tachyarrhythmias (VA). We aimed to investigate the antiarrhythmic and molecular mechanisms of ranolazine in db/db mouse hearts with acute IR injury. Ranolazine was administered for 1 week before coronary artery ligation. Diabetic db/db and control db/+ mice were divided into ranolazine-given and -nongiven groups. IR model was created by 15-min left coronary artery ligation and 10-min reperfusion. In vivo electrophysiological studies showed that the severity of VA inducibility was higher in db/db mice than control (db/ +) mice. Ranolazine suppressed the VA inducibility and severity. Optical mapping studies in Langendorff-perfused hearts showed that ranolazine significantly shortened action potential duration, Cai transient duration, Cai decay time, ameliorated conduction inhomogeneity, and suppressed arrhythmogenic alternans induction. Western blotting studies showed that the expression of pThr17-phospholamban, calsequestrin 2 and voltage-gated sodium channel in the IR zone was significantly downregulated in db/db mice, which was ameliorated with ranolazine pretreatment and might play a role in the anti-arrhythmic actions of ranolazine in db/db mouse hearts with IR injury.


Modern imaging methods in paediatric breast examination.
To diagnose premature or prepubertal breast development or breast diseases. Harmless, non-invasive examinations were conducted on young girls by the use of ultrasound and liquid crystal thermography with discs of various sensitivity. The study was conducted at the Radiological Department of the Postgraduate Medical University in Budapest, Hungary. The study entailed examination of 283 patients, all under age 14, of the paediatric gynaecological ward and the outpatient service who had breast problems. Aspiration cytology or surgical intervention were used only in rare cases. The outcome was measured based on the accuracy and expediency of the diagnostic procedures. The most frequent problems observed were precocious breast development, precocious pubertal development and asymmetric breasts. Precocious thelarche was observed in 117 patients, four patients were found to have cysts, and there were 59 cases of inflammation or abscess. Liquid crystal thermography and ultrasound proved to be sufficient and accurate means of diagnosis breast problems.


Improving the donor site cosmesis of the latissimus dorsi flap.
A modification in the design of the pedicled latissimus dorsi musculocutaneous flap is described that aims to minimize the cosmetic morbidity of its donor site. The implications of this variation are discussed with particular reference to use of the flap in postmastectomy reconstruction.


Photocatalytic Alkylation of C(sp3 )-H Bonds Using Sulfonylhydrazones.
The ability to construct C(sp3 )-C(sp3 ) bonds from easily accessible reagents is a crucial, yet challenging endeavor for synthetic organic chemists. Herein, we report the realization of such a cross-coupling reaction, which combines N-sulfonyl hydrazones and C(sp3 )-H donors through a diarylketone-enabled photocatalytic hydrogen atom transfer and a subsequent fragmentation of the obtained alkylated hydrazide. This mild and metal-free protocol was employed to prepare a wide array of alkyl-alkyl cross-coupled products and is tolerant of a variety of functional groups. The application of this chemistry further provides a preparatively useful route to various medicinally-relevant compounds, such as homobenzylic ethers, aryl ethyl amines, β-amino acids and other moieties which are commonly encountered in approved pharmaceuticals, agrochemicals and natural products.


Effect of novel glucose lowering agents on non-alcoholic fatty liver disease: A systematic review and meta-analysis.
The efficacy of novel glucose-lowering drugs in treating non-alcoholic fatty liver disease (NAFLD) in patients with and without type-2 diabetic patients (T2DM) remains unclear. To conduct a meta-analysis to evaluate the efficacy of 3 novel glucose-lowering drug classes, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 (SGLT2) inhibitors, and dipeptidyl-peptidase-4 (DPP4) inhibitors on hepatic parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-Glutamyl Transferase (GGT), Bilirubin, and FIB-4 (Fibrosis). MEDLINE was searched from inception through October 2021 for randomized placebo or active glucose-lowering drug-controlled trials. A random-effects model was used to pool the results. A p-value of less than or equal to 0.05 was considered significant. Results were presented as weighted mean differences (WMD) and corresponding 95% confidence intervals (CIs). Our pooled analysis consisted of 40 studies. A significant reduction was seen in AST with SGLT2 inhibitors (WMD = -2.31 IU/L, 95%CI: -3.16 to -1.47 IU/L, P < 0.00001) and GLP-1RA (WMD = -3.29 IU/L, 95%CI: -5.98 to -0.61 IU/L, P = 0.02). Similarly, significant reduction was seen in ALT with SGLT2 inhibitors (WMD = -5.93 IU/L, 95%CI: -7.70 to -4.16 IU/L, P < 0.00001) and GLP-1RAs (WMD = -9.92 IU/L, 95%CI: -19.89 to 0.05 IU/L, P = 0.05). In contrast, DPP-4 inhibitors showed no significant reduction in AST (WMD = -3.20 IU/L, 95%CI: -11.13 to 4.73 IU/L, P = 0.43) or ALT (WMD = -4.81 IU/L, 95%CI: -15.83 to 6.21 IU/L, P = 0.39). A significant reduction in GGT was seen with SGLT2 inhibitors (WMD = -6.49 IU/L, 95%CI: -11.09 to -1.89 IU/L, P = 0.006) and GLP-1RAs (WMD = -12.38 IU/L, 95%CI: -15.69 to -9.07 IU/L, P < 0.00001). However, significant results were not observed with DPP-4 inhibitors (WMD = -0.92 IU/L, 95%CI: -5.80 to 3.96 IU/L, P = 0.71). There was a statistically significant reduction in FIB-4 index with SGLT2 inhibitors (WMD = -0.21, 95%CI: -0.40 to -0.03, P = 0.02) and GLP-1 RA (WMD = -0.15, 95%CI: -0.29 to 0.00, P = 0.05). Lastly, SGLT2 inhibitors led to a significant change in bilirubin levels (WMD = 2.03, 95%CI: 0.76 to 3.30, P = 0.002) while the change in bilirubin was not significant with GLP-1 agonists (WMD = -0.21, 95%CI: -1.09 to 0.66, P = 0.63) and DPP-4 inhibitors (WMD = 0.14, 95%CI: -1.55 to 1.83, P = 0.87). SGLT2 inhibitors and GLP-1 agonists have a beneficial effect on hepatic parameters in patients with NAFLD. However, further research is needed to evaluate the effect of DPP-4 inhibitors on hepatic function properly.


Priming of the sweat glands explains reflex sweating in the heat.
The purpose of this study was to determine whether reflex sweating during isometric handgrip exercise (IHG) in the heat was due to a priming effect in the sweat glands or an increase in skin temperature. Ten male subjects completed four trials where they performed IHG for three minutes at 40% of their maximal voluntary contraction (MVC). The four trials included: (1) a control trial in thermoneutral conditions (23±1°C), (2) after sitting in hyperthermic conditions (35±1°C) for 30 min, (3) a local heating trial after having their non-exercising arm wrapped in a heat pad that maintained forearm skin temperature at ~35°C for 30 min, 4) and after pilocarpine iontophoresis to a 5 cm(2) area of the forearm. The sweating rate (SR), as measured by resistance hygrometry, was not significantly different (P>0.05) from baseline during IHG in either the control or local heating trial, but was significantly increased (P<0.05) from baseline during the hyperthermic and pilocarpine trials. Baseline SR values of the hyperthermic and pilocarpine trials (~0.25mg/cm(2)/min) were significantly greater than the control and local heating trials (~0.05 mg/cm(2)/min). These results suggest that reflex sweating in the heat during IHG is primarily due to a priming effect in the sweat glands and not because of an increase in skin temperature.


14-3-3 eta isoform colocalizes TDP-43 on the coarse granules in the anterior horn cells of patients with sporadic amyotrophic lateral sclerosis.
The immunolocalization of the 14-3-3 eta isoform in the anterior horn cells (AHCs) of patients with sporadic amyotrophic lateral sclerosis (ALS) and controls was examined. Compared with the immunolocalization of other 14-3-3 isoforms, the immunolocalization of the 14-3-3 eta isoform was either synaptic at the periphery of AHCs, spindle-shaped in neurites, or granular in the cytoplasm. By double labeling with phosphorylated (p-)TDP-43, the transactivation response DNA binding protein of 43kDa (TDP-43) demonstrated frequent colocalization of the 14-3-3 eta isoform in granular structures (90%) and spindle-shaped structures (85.4%), but not in p-TDP-43-positive round inclusions. It is speculated that the 14-3-3 eta isoform is associated with not only a synaptic pathology of ALS but also TDP-positive small lesions in the cytoplasm and neurites. The absence of eta-like immunoreactivity in p-TDP-43-positive large inclusions suggests the restricted relevance of the 14-3-3 eta isoform during ALS pathogenesis to some phases of the p-TDP pathology.


The eye as a window to inborn errors of metabolism.
Ocular manifestations in inborn errors of metabolism occur in many diseases and may be associated with any part of all eye components. In a minority of diseases it is possible to attribute the eye symptoms to a single hereditary pathogenetic mechanism. More often the aetiological relationship of the ocular defects to the metabolic disease is unknown. Diverse pathogenetic mechanisms may act via a common pathological pathway inducing ocular damage. The occurrence of eye abnormalities in metabolic disorders suggests that they are associated with direct toxic actions, errors of synthetic pathways or deficient energy metabolism. In this review, metabolic disorders with major abnormalities in the cornea, lens, retina and optic nerve are presented. In all cases, an appropriate combined approach by the ophthalmologist, paediatrician/neurologist, geneticist and clinical biochemist is the only way to diagnostic success.


A comparison of the MacAndrew Alcoholism Scale and the Michigan Alcoholism Screening Test in a sample of problem drinkers.
In a sample of problem drinkers, the Michigan Alcoholism Screening Test performed best with subjects who identified themselves as alcoholics, whereas the MacAndrew Alcoholism Scale worked best with patients in the more advanced stages of alcoholism.


Assessing the competitiveness of listed Chinese high-growth companies in the STAR market.
This paper aims to assess the competitiveness of 68 high-growth enterprises listed on China's STAR market and explore the combination of antecedent conditions that led to their listing using fuzzy set qualitative comparative analysis. The interpretive structure model was utilized to identify the factors influencing their competitiveness, and the listing index weight for the STAR market was determined using the analytic hierarchy process. The competitiveness of the listed enterprises was found to be promising, with new energy, next-generation IT, and high-end equipment manufacturing being the most prominent fields. However, energy conservation and environmental protection exhibited relatively weak listed competitiveness. The listing of these enterprises was the result of multiple factors rather than a single factor. The listing paths of high-growth enterprises in China were classified into three types: well-operated with high technical competence and innovation-led, high-profit with low growth and innovation, and large-scale, high-profit, and innovation-led.


Prescription of nCPAP and nBIPAP in obstructive sleep apnoea syndrome: Italian experience in 105 subjects. A prospective two centre study.
Nasal continuous positive airway pressure (nCPAP) is the current treatment of obstructive sleep apnoea syndrome (OSAS). The indications of bilevel pressure support ventilation (BIPAP PSV) in OSAS patients remain controversial. The purpose of this investigation was to verify the frequency of prescription of BIPAP PSV in a group of OSAS patients when CPAP was ineffective or not tolerated during titration. The study included 286 consecutive patients > or = 18 years of age referred to two Sleep laboratories for sleep related breathing disorders (SRBD) between December 1994 and November 1995. Of these, 130 patients were enrolled and 105 (88 males, 77 females) with moderate to severe OSAS completed the study and were finally analysed. After a full night diagnostic polysomnography (PSGD), patients had a second full night PSG under nCPAP (PSGT). If nCPAP was not tolerated, or failed to correct breathing abnormalities during sleep, a second PSGT was performed, using a BIPAP PSV. Our study shows that nCPAP (mean 8.5 +/- 2.0 cmH20) was considered a satisfactory therapy in 81 patients (77%). Twenty four (23%) required BIPAP PSV (mean IPAP 13.9 +/- 2.9 cmH20). We found the highest prevalence of BIPAP in patients with OSAS associated to obesity hypoventilation syndrome (OHS) (11 of 17) and in OSAS associated to chronic obstructive pulmonary disease (COPD) (nine of 16). Patients treated with BIPAP PSV were more obese and had a higher PaCO2 and sleep-related desaturations and a lower FEV1, FVC, FEV1/FVC and PaO2. In conclusion our study shows that CPAP therapy in the effective therapeutic option in the majority of patients with OSAS. There is a subset of patients with OSAS associated to COPD or to OHS in whom BIPAP PSV may be a better treatment modality.


Bacterial adhesion on biomedical surfaces covered by yttria stabilized zirconia.
The aim of this study was to compare the bacterial adhesion of Staphylococcus spp. on Ti-6Al-4V with respect to Ti-6Al-V modified alloys with a set of Cubic yttria stabilized zirconia (YSZ) and Ag-YSZ nanocomposite films. Silver is well known to have a natural biocidal character and its presence in the surface predicted to enhance the antimicrobial properties of biomedical surfaces. Microbial adhesion tests were performed using collection strains and twelve clinical strains of Staphylococcus aureus and Staphylococcus epidermidis. The adherence study was performed using a previously published protocol by Kinnari et al. Both collection strains and clinical isolates have shown lower bacterial adhesion to materials modified with respect to the alloy Ti-6Al-4V and the modification with silver reduced the bacterial adhesion for most of all the strains studied. Moreover the percentage of dead bacteria have been evaluated, demonstrating increased proportion of dead bacteria for the modified surfaces. Nanocrystalline silver dissolves releasing both Ag(+) and Ag(0) whereas other silver sources release only Ag(+). We can conclude that YSZ with nanocrystalline silver coating may lead to diminished postoperative infections and to increased corrosion and scratch resistance of YSZ incorporating alloys Ti-6Al-4V.


Pilon fractures: assessment and treatment.
The treatment of high-energy intra-articular fractures of the tibial plafond involves many potential complications. A protocol has been developed. This protocol recognizes the importance of the surrounding soft tissues and is based on sound principles and thorough clinical experience. This article discusses this protocol and its use and explains why it is now more widely accepted.


A study on the relationship between intraglandular arterial distribution and thyroid lobe shape: implications for biotechnology of a bioartificial thyroid.
We have recently hypothesized that structural and secretory components of the adult human thyroid gland maintain constant reciprocal and geometrical relationships, even if changes occur in the three-dimensional (3D) architecture of any of these elements. This means that thyroid morphology could be studied from the point of view of a 3D topology. As a consequence, we have investigated anatomical aspects that could support this assumption. In the present study, we show that the presence of a constant relationship can be demonstrated between the vascular arrangement of the gland, including the extension of intraglandular arterial fields, arterial anastomoses and arterial calibers, and the shape as well as volume of the thyroid. Specifically, a statistically significant difference has been found between the network amplitudes of the superior and inferior thyroid arteries in relation to either a conic or an ellipsoidal geometry of the thyroid lobe. In addition, a direct relationship has been implicated between the distribution of arterial anastomoses and the behavior of the lobe as a single hemodynamic unit. Finally, a statistically significant correlation has been observed between average arterial caliber of the inferior thyroid artery and thyroid volume. On the basis of these results, we propose a model of architectural assembly between stromal and parenchymal elements of the adult thyroid that might prove useful in designing a bioartificial gland ex situ. Potential clinical applications of this principle in regenerative medicine of other endocrine organs are highlighted.


A comparison of quality of life and satisfaction of women with early-stage breast cancer treated with breast conserving therapy vs. mastectomy in southern China.
The purpose of this study was to compare the quality of life (QoL) and overall satisfaction with treatment of women with stage T1-2N0M0 breast cancer treated with breast conserving therapy (BCT) or mastectomy (MAS) in southern China. Functional assessment of cancer therapy-breast, traditional Chinese version 4 (FACT-B), was administered to 180 patients with stage T1-2N0M0 breast cancer (82 BCT and 98 MAS) treated between July 2000 and July 2008. The two groups differed in tumor pathology and how axillary lymph nodes were treated (sentinel node biopsy vs. dissection), while other disease and socioeconomic characteristics were similar. The median follow-up after completion of radiotherapy was 60 months in the BCT group, and 65 months in the MAS group. The scores of the physical, functional, and emotional domains and breast-specific concerns of FACT-B were not significantly different between the groups. The social domain score of the BCT group was significantly greater than those of the MAS group. Patients who underwent BCT did not report better QoL than those who received MAS, but BCT patients experienced easier social adjustment.


SPARC in cancer-associated fibroblasts is an independent poor prognostic factor in non-metastatic triple-negative breast cancer and exhibits pro-tumor activity.
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and lacks specific targeted therapeutic agents. The current mechanistic evidence from cell-based studies suggests that the matricellular protein SPARC has a tumor-promoting role in TNBC; however, data on the clinical relevance of SPARC expression/secretion by tumor and stromal cells in TNBC are limited. Here, we analyzed by immunohistochemistry the prognostic value of tumor and stromal cell SPARC expression in 148 patients with non-metastatic TNBC and long follow-up (median: 5.4 years). We also quantified PD-L1 and PD-1 expression. We detected SPARC expression in tumor cells (42.4%), cancer-associated fibroblasts (CAFs; 88.1%), tumor-associated macrophages (77.1%), endothelial cells (75.2%) and tumor-infiltrating lymphocytes (9.8%). Recurrence-free survival was significantly lower in patients with SPARC-expressing CAFs. Multivariate analysis showed that SPARC expression in CAFs was an independent prognostic factor. We also detected tumor and stromal cell SPARC expression in TNBC cytosols, and in patient-derived xenografts and cell lines. Furthermore, we analyzed publicly available single-cell mRNA sequencing data and found that in TNBC, SPARC is expressed by different CAF subpopulations, including myofibroblasts and inflammatory fibroblasts that are involved in tumor-related processes. We then showed that fibroblast-secreted SPARC had a tumor-promoting role by inhibiting TNBC cell adhesion and stimulating their motility and invasiveness. Overall, our study demonstrates that SPARC expression in CAFs is an independent prognostic marker of poor outcome in TNBC. Patients with SPARC-expressing CAFs could be eligible for anti-SPARC targeted therapy.


Getting clinical authors--even during healthcare reform.
Prospective writers are finding it harder to write than ever before. Fear of rejection is not the greatest problem any more; instead, the obstacle is finding the time and energy to write. This article describes the problems clinical authors are experiencing during this era of healthcare reform and timely strategies which can help.