Yes-Associated Protein in Kupffer Cells Enhances the Production of Proinflammatory Cytokines and Promotes the Development of Nonalcoholic Steatohepatitis.
Yes-associated protein (YAP) plays an important role in hepatocarcinogenesis, although the potential role of YAP in non-neoplastic liver diseases remains largely unknown. We report herein that YAP in Kupffer cells (KCs) enhances the production of proinflammatory cytokines and promotes the development of nonalcoholic steatohepatitis (NASH). Our data show that the expression of YAP is significantly increased in KCs of wild-type mice fed a high-fat diet (HFD). We generated mice with macrophage/monocyte-specific deletion of YAP (YAPϕKO ) or Toll-like receptor 4 (TLR4; TLR4ϕKO ), and animals were fed an HFD or treated with lipopolysaccharide (LPS). Our data showed that YAPϕKO mice fed an HFD exhibited lower serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels and less hepatic inflammation when compared to their littermate controls. LPS treatment induced accumulation of YAP in KCs in vitro and in mice, which was prevented by macrophage/monocyte-specific deletion of TLR4 (TLR4ϕKO ). LPS transcriptionally activates YAP through activator protein 1 in macrophages/KCs. LPS-induced YAP further enhances expression of proinflammatory cytokines (including monocyte chemoattractant protein 1, tumor necrosis factor alpha, and interleukin 6) through YAP association with the TEA domain-binding motif in the promoter region of inflammatory cytokines. Forced overexpression of active YAP (YAP5SA) in KCs enhanced the production of proinflammatory cytokines. Treatment of HFD-fed mice with verteporfin inhibited KC activation, reduced liver inflammation, and decreased serum ALT/AST levels. Analyses of liver tissues from NASH patients reveal that YAP is increased in KCs and that level of YAP in human liver tissues is positively correlated with expression of proinflammatory cytokines. This study describes an important role of YAP in KCs for regulation of liver inflammation in NASH. Our findings suggest that inhibition of YAP may represent an effective therapeutic strategy for NASH treatment.


Actual management of ductal carcinoma in situ of the breast.
Ductal carcinoma in situ (DCIS) represents a premalignant, non-invasive intraductal carcinoma of the breast. About 30% of all mammographically detected breast cancers contain DCIS. Due to the increased use of mammography during the last 20 years the incidence of DCIS has dramatically risen. Histologically it represents a heterogenous group of potentially malignant lesions. The prognosis of DCIS is excellent, but the optimal management of the disease still remains controversial. This review summarizes the results of the latest randomized trials and retrospective analyses investigating the optimal therapeutic strategies in the treatment of DCIS. In addition, it presents a range of treatment options on the basis of the guidelines of the German gynecological oncology group (AGO) 2008.


Minimally invasive endoscopically assisted remodelation (MEAR) of sagittal craniosynostosis: an alternative technique to open and endoscopic procedures with cranial orthosis time span reduction.
Sagittal craniosynostosis represents the most frequent simplex skull suture pathology. There are currently several operative approaches to this defect. Minimally invasive techniques are preferred for young infants. Since July 2017, we have employed endoscopically assisted craniectomies followed by cranial orthosis. Gradually, we have developed our modified technique, the minimally invasive endoscopically assisted remodelation (MEAR). MEAR is a combination of principles gained from classical cranial vault remodeling techniques and minimal invasive approaches. The long and wider lateral osteoectomies performed in the parietal and occipital bones along with loosening of the periosteum and dura adhesions at the lambdoid sutures lead to early correction of parieto-occipital dimensions. Thirty-one consecutive patients with scaphocephaly underwent MEAR. The median preoperative cephalic index of 67 units (P25:63.3, P75:70) was improved to a median postoperative cephalic index of 77 units (P25:75, P75: 81). Sufficient correction was achieved in all patients. Cranial orthosis was needed for a median of 1.5 months (P25:1, P75:2). We had no major surgical complications in this pilot series. With MEAR, we have achieved good cosmetic results. Duration of cranial orthosis was significantly shortened compared to conventional endoscopic-assisted procedures.


A new model of resorbable device degradation and drug release: transient 1-dimension diffusional model.
In the framework of resorbable devices, an increased demand for a better reliability in drug delivery systems emerged, based on resorbable polymers degradation control. These points influenced researchers to replace the trial-and-error approaches with model-based ones. In this context, we developed a transient 1-dimension model for degradation and drug release of resorbable polymeric drug loaded systems. Such model is thought to be applied to design specific devices based on the expected degradation time and drug delivery rates. It is based on the detailed conservation equations taking into account main physical-chemical parameters involved in polymer degradation and in drug release, all independently estimated. The model leads to a system of partial differential equations solved numerically, which predictions were verified through both literature and our data. Data of different authors, various systems and directly generated data were matched by model predictions. Reliability of parameter estimation procedures was also confirmed by accelerated life tests.


Targeting GLS1 to cancer therapy through glutamine metabolism.
Glutamine metabolism is one of the hallmarks of cancers which is described as an essential role in serving as a major energy and building blocks supply to cell proliferation in cancer cells. Many malignant tumor cells always display glutamine addiction. The "kidney-type" glutaminase (GLS1) is a metabolism enzyme which plays a significant part in glutaminolysis. Interestingly, GLS1 is often overexpressed in highly proliferative cancer cells to fulfill enhanced glutamine demand. So far, GLS1 has been proved to be a significant target during the carcinogenesis process, and emerging evidence reveals that its inhibitors could provide a benefit strategy for cancer therapy. Herein, we summarize the prognostic value of GLS1 in multiple cancer type and its related regulatory factors which are associated with antitumor activity. Moreover, this review article highlights the remarkable reform of discovery and development for GLS1 inhibitors. On the basis of case studies, our perspectives for targeting GLS1 and development of GLS1 antagonist are discussed in the final part.


Understanding the benefit of metformin use in cancer treatment.
Biguanides have been developed for the treatment of hyperglycemia and type 2 diabetes. Recently, metformin, the most widely prescribed biguanide, has emerged as a potential anticancer agent. Epidemiological, preclinical and clinical evidence supports the use of metformin as a cancer therapeutic. The ability of metformin to lower circulating insulin may be particularly important for the treatment of cancers known to be associated with hyperinsulinemia, such as those of the breast and colon. Moreover, metformin may exhibit direct inhibitory effects on cancer cells by inhibiting mammalian target of rapamycin (mTOR) signaling and protein synthesis. The evidence supporting a role for metformin in cancer therapy and its potential molecular mechanisms of action are discussed.


Knowledge about the relationship between smoking and blindness in Canada, the United States, the United Kingdom, and Australia: results from the International Tobacco Control Four-Country Project.
Smoking is causally associated with certain prevalent visually impairing eye diseases, including age-related macular degeneration and cataract. Studies have found that people are afraid of "going blind" and may be motivated to quit smoking if they know that vision loss is associated with smoking behavior. A random-digit dialed telephone survey was used to measure health knowledge of adult smokers in Canada (n = 2,765), the United States (n = 3,178), the United Kingdom (n = 2,767), and Australia (n = 2,623) as part of the International Tobacco Control Four-Country Project. A low proportion of smokers from Canada (13.0%), the United States (9.5%), and the United Kingdom (9.7%) believed that smoking can cause blindness. In contrast, 47.2% of Australian smokers believed that smoking causes blindness. Australia was the only country during the sampling period to have national awareness campaigns about smoking and its effects on eye health. These findings point to the need across countries to educate the public on this important consequence of smoking. There is an opportunity for the public health and eye health communities to work to educate the public about the impacts smoking has on eye health to improve quit rates and help discourage people from starting to smoke.


Transcatheter and Surgical Aortic Valve Replacement Outcomes for Patients with Chronic Heart Failure.
To determine in-hospital outcomes and assess high-risk groups among chronic heart failure (CHF) patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). A retrospective analysis of the Nationwide Inpatient Sample database from January 2012 to September 2015 was performed. Hospitals across the United States that offer TAVRs or SAVRs. Adults with a diagnosis of CHF and AS. The patients underwent either TAVR or SAVR. Totals of 5,871 and 4,008 CHF patients underwent TAVR and SAVR, respectively. TAVR patients were significantly older, more were female, and had a higher comorbidity burden. No significant differences in in-hospital mortality were noted between TAVR and SAVR. However, mean length of stay was significantly longer by 3.5 days in the SAVR group, as was the mean total cost. With the exception of complete heart block, permanent pacemaker implantation, and vascular complications, the majority of postoperative events were higher among the SAVR group. Multivariate regression analysis identified postoperative cardiac, respiratory and renal complications as significant predictors of in-hospital mortality for both groups. Additionally, age ≥75 years and vascular complications were significant predictors of mortality for patients undergoing TAVR. Among CHF patients with symptomatic AS, TAVR had similar in-hospital mortality rate compared with SAVR despite higher comorbidity burden. TAVR patients are at a lower risk of cardiovascular, respiratory, and renal complications and might lead to reduced length of hospital stay and cost. Hence, TAVR may be a safer option in this population.


Arthroscopic assisted PCL reconstruction: a technical note on potential neurovascular injury related to drill bit configuration.
Neurovascular injury is a potential complication during arthroscopic assisted or open posterior cruciate ligament (PCL) reconstruction. The anatomical configuration of the posterior tibia and the square configuration of the end of commonly used drill bits require special attention. One portion of the drill bit may cut out of the tibia < or = 20 mm distal to the exit point of the guide wire. The sharp square edges of these drill bits have a greater potential to traumatize adjacent soft tissue and to increase the risk of neurovascular damage. This risk may be decreased by using a tapered drill bit, an oscillating drill, and careful elevation and retraction of the overlying soft tissue.


S100B serum level: A relevant biomarker for the management of non-traumatic headaches in emergency care?
The diagnostic of primary or secondary headaches in emergency units is mostly based on brain imaging, which is expensive and sometimes hardly accessible. An increase in serum S100B protein has already been found in several neurological conditions inducing brain damage. The objective of this study was to assess the diagnostic performance of S100B serum assay to distinguish primary and secondary headaches among patients with non-traumatic headaches in the emergency department. This was a phase 2, prospective, monocentric diagnostic study. Eighty-one adult patients with non-traumatic headaches in the emergency department were included. In addition to the usual management, a blood assay of the S100B protein was performed in the emergency department, as well as a brain MRI between 48 and 96 h if not performed during the initial management. The primary or secondary headache diagnosis was made at one month by an expert committee, blindly of the results of the S100B assay. The primary outcome was the blood assay of the S100B protein. There was 63 patients for analysis in the primary headache group and 17 in the secondary headache group. The S100B protein assay was significantly higher in secondary headaches than primary headaches, with an AUC of the ROC curve of 0.67. The optimal threshold of 0.06 μg.L-1 allowed to obtain those diagnostic characteristics: sensitivity 75% [48; 93], specificity 62% [48; 74], PPV 35% [20; 54] and NPV 90% [76; 97]. The association between the S100B protein level and the onset of pain was significantly higher for patients with headaches <3 h. The assay of the S100B protein could be useful in the management of this pathology in emergencies. Future studies taking into account dosing time and etiologies could be conducted in order to refine its use in practice.


Determinants of mental health outcomes among people with and without diabetes during the COVID-19 outbreak in the Arab Gulf Region.
To determine the prevalence and factors associated with depression and anxiety among people with and without diabetes during the coronavirus disease 2019 (COVID-19) outbreak. A cross-sectional questionnaire-based study collecting demographic and mental health data from 2166 participants living in the Arab Gulf region (568 with diabetes, 1598 without diabetes). Depression and anxiety were assessed using the 9-item Patient Health Questionnaire and the 7-item Generalized Anxiety Disorder scale, respectively. The prevalence of depression and anxiety symptoms were 61% and 45%, in people with diabetes (PWD) and 62% and 44%, respectively, in people without diabetes. PWD who have had their diabetes visit canceled by the clinic were more likely to report depression and anxiety symptoms than those without diabetes (odds ratio [95% confidence interval]: 1.37 [1.02, 1.84] and 1.37 [1.04, 1.80], for depression and anxiety; respectively). PWD who had no method of telecommunication with their health care providers (HCP) during the pandemic, PWD with A1C of ≥ 10%, women, employees (particularly HCPs), students, unmarried individuals, and those with lower income were more likely to report depression and/or anxiety symptoms (all P < 0.01). Fear of acquiring the coronavirus infection; running out of diabetes medications; or requiring hospitalization for hypoglycemia, hyperglycemia, or diabetic ketoacidosis; and lack of telecommunication with HCPs were all associated with significantly higher odds of having depression and anxiety symptoms among PWD. The remarkably high prevalence of depression and anxiety symptoms during the COVID-19 pandemic, particularly among subgroups of PWD, calls for urgent public health policies to address mental health during the pandemic and reestablish health care access for PWD.


Effects of Two Physical Activity Interventions on Sleep and Sedentary Time in Pregnant Women.
Pregnancy is often associated with poor sleep and high sedentary time (SED). We investigated the effect of physical activity (PA) interventions on sleep and SED in pregnant women. A secondary analysis of a randomized controlled trial (n = 219) explored the effect of structured supervised exercise training (EXE) or motivational counseling on PA (MOT) compared to standard prenatal care (CON) on sleep and SED during pregnancy. Three times during pregnancy, sleep was determined by the Pittsburgh Sleep Quality Index (PSQI) and SED by the Pregnancy Physical Activity Questionnaire (PPAQ). Also, a wrist-worn consumer activity tracker measured sleep and SED continuously. Data from the activity tracker confirmed that sleep time decreases, and SED increases by approx. 30 and 24 min/day, respectively, from baseline (maximum gestational age (GA) week 15) to delivery. Compared to CON, the global PSQI score was better for EXE in GA week 28 (-0.8 [-1.5; -0.1], p = 0.031) and for both EXE and MOT in GA week 34 (-1 [-2; -0.5], p = 0.002; -1 [-2; -0.1], p = 0.026). In GA week 28, SED (h/day) from PPAQ was lower in EXE compared to both CON and MOT (-0.69 [-1; -0.0], p = 0.049; -0.6 [-1.0; -0.02], p = 0.042). In conclusion, PA interventions during pregnancy improved sleep quality and reduced SED.


Clinical predictors in obstructive sleep apnoea patients with calibrated cephalometric analysis--a new approach.
Utilization of a new method to accurately quantify differences in cephalometric parameters between obstructive sleep apnoea (OSA) and normal patients, and to identify good predictors for OSA. To illustrate the ethnic differences in cephalometry. This prospective study involves 106 South-east Asians. A calibrated catheter is inserted into the upper airway during standard cephalometry to obtain the precise magnification and allow exact measurement of anatomical parameters of cephalometry in both erect and supine positions. The OSA patients have longer lower-facial length, narrower skull base, shorter and receding mandible, smaller posterior airway space (PAS), narrower retropalatal space, longer and thicker soft palate, smaller hard and soft palate angles longer tongue length and more inferiorly displaced hyoid. For the palatal level, retropalatal distance of 11.2 mm cut-off/predictive value for male (receiver operating characteristics (ROC) = 0.8414 with PPV = 77.46, NPV = 90.00) and 5.5 mm for female (ROC = 0.9180 with PPV = 100.00, NPV = 84.21) at erect position were selected. For retrolingual level, erect PAS of 10.1 mm cut-off/predictive value for male (ROC = 0.7000 with PPV = 78.38, NPV = 37.78), 5.3 mm for female (ROC = 0.7227 with PPV = 75.00, NPV = 75.00) were selected. Our study showed that South-east Asians have different cephalometric values compared with White people, Black people and Hispanics. This new method of cephalometry using a calibrated catheter provides an accurate and simple method of obtaining precise cephalometric measurements. There is no cephalometric data on OSA from South-east Asia available. These results suggested that surgeons managing OSA patients and using cephalometry as a diagnostic method should have a set of normative and OSA cephalometric values that apply to their local populations.


Extent of prostate-specific antigen contamination in the Spanish section of the European Randomized Study of Screening for Prostate Cancer (ERSPC).
The performance of tests outside prostate cancer screening trials (PSA contamination) may affect their statistical power. The present study addressed the extent of PSA contamination in the Spanish section of the European Randomized Study of Screening for Prostate Cancer (ERSPC) and its impact on biopsy performance and prostate cancer detection. Data linkage was performed to address screening-related interventions outside the study. Four databases were used: (1) Spanish ERSPC database (n=4278), (2) laboratory database with all PSA determinations (n=31,140), (3) database of 1608 prostate biopsies, and (4) records of all prostate cancers (n=819) diagnosed at our centre. PSA contamination, biopsy performance, and cancer detection rates were calculated. Median follow-up time was 6.6 yr. A total of 2201 PSA determinations were performed for 1253 men. Cumulative PSA contamination was 29.3% (17% in the control arm during the first 4 yr). A higher proportion of men undergoing biopsies was found in the screening arm (21.3% vs. 2.9% in the control arm, p<0.0001). Similarly, higher cancer detection rates were found in the screening (4.7% vs. 1.2% in the control arm, p<0.0001). In our experience, the PSA contamination rate has increased during the last years, but its impact on biopsy performance and cancer detection in the control arm of the trial is limited and not likely to compromise the statistical power of the ERSPC trial.


Random coupling model of turbulence as a classical Sachdev-Ye-Kitaev model.
We point out that a classical analog of the Sachdev-Ye-Kitaev (SYK) model, a solvable model of quantum many-body chaos, was studied long ago in the turbulence literature. Motivated by the Navier-Stokes equation in the turbulent regime and the nonlinear Schrödinger equation describing plasma turbulence, in which there is mixing between many different modes, the random coupling model has a Gaussian-random coupling between any four of a large number N of modes. The model was solved in the 1960s, before the introduction of large-N path-integral techniques, using a method referred to as the direct interaction approximation. We use the path integral to derive the effective action for the model. The large-N saddle gives an integral equation for the two-point function, which is very similar to the corresponding equation in the SYK model. The connection between the SYK model and the random coupling model may, on the one hand, provide new physical contexts in which to realize the SYK model and, on the other hand, suggest new models of turbulence and techniques for studying them.


Bacteriology of upper urinary tract stones.
Extensive cultures of stones and urine were performed in 215 patients who underwent an operation for upper urinary tract calculi. Microorganisms could be cultured from the stone in 1 of every 3 patients. Despite the extended culture technique urease-producing microorganisms could be cultured from the stone in only 48% of the patients with calculi that contained magnesium ammonium phosphate. This finding suggests that an infection with urease-producing microorganisms is not obligatory for the formation of this type of stone. Of the patients with calcium oxalate phosphate stones 32% had positive stone cultures, which distinguished them from patients with pure calcium oxalate stones, only 8% of whom had a positive stone culture (p less than 0.001).


Low-grade endometrial stromal sarcoma: A Turkish uterine sarcoma group study analyzing prognostic factors and disease outcomes.
To investigate factors associated with refractory disease, recurrence, or death as well as disease-free survival (DFS) and overall survival (OS) in low-grade endometrial sarcoma (LGESS). A multi-institutional, retrospective study was conducted in a total of 124 patients, who received a curative-intent surgery. The exclusion criteria were as follows: i) history of any other invasive disease; ii) neoadjuvant therapy; iii) fertility sparing surgery; iv) a different diagnosis after review of the slides. All patients underwent hysterectomy, 96% had bilateral salpingo-oophorectomy, and 65% had lymphadenectomy. Twelve (14.8%) of 81 patients undergoing lymphadenectomy had lymph node (LN) metastasis. Of those, 8 (9.8%) had pelvic LN metastasis whereas 4 (5.6%) had isolated paraaortic LN metastasis. Six of 8 (75%) patients with positive pelvic LNs had concurrent paraaortic LN metastasis. Among 124 patients, 3 patients (2.4%) had refractory disease following primary therapy. During a median follow-up of 45.5 months, 27 (22.3%) of 121 patients who achieved complete remission after primary therapy developed recurrence, and 10 patients (8.1%) died of disease. The 3-year DFS and OS were 76.9% and 93.8%, respectively. Stage was the sole independent prognostic factor in the whole cohort. When analyzing factors within subgroups of stage I and stage ≥II, there was no significant prognostic factor for stage I; however, lymphadenectomy and adjuvant chemotherapy were significantly associated with disease outcomes for stage ≥II. While lymphadenectomy was related with improved DFS, chemotherapy was associated with poor DFS and OS. The risk of LN metastasis at pelvic as well as paraaortic lymphatic basins is not negligible to omit lymphadenectomy in stage ≥II LGESS. Moreover, lymphadenectomy provides significant DFS advantage in patients with extrauterine disease.


Effects of prostaglandin E1 on the positive inotropic actions of noradrenaline, nerve stimulation and calcium in the isolated blood-perfused papillary muscle of the dog.
The effects of PGE1 on the dog heart were studied using the blood-perfused sinus node and papillary muscle preparations isolated separately from the same animal. PGE1 administered into the papillary muscle artery as bolus injections in doses of 1-1000 ng caused a dose-dependent increase of the developed tension and dT/dt of the papillary muscle. The effect was not inhibited by the beta-adrenoceptor blocking agent pindolol. PGE1 injected into the sinus node artery in doses of 3-300 ng did not change the rate of contraction of the sinus node preparation. PGE1 in the blood concentrations of 4.4 X 10(-9) to 1.7 X 10(-7) M enhanced the positive inotropic responses to noradrenalin and field stimulation as well as to calcium. The influence of PGE1 on the positive inotropic effect of perivascular nerve stimulation was not consistent: the action of perivascular nerve stimulation was enhanced by PGE1 in the majority of preparations but was reduced in one third of preparations. PGE1 in the same blood concentrations as used in the papillary muscle significantly depressed the positive chronotropic responses to noradrenaline and dopamine. The present results indicate that PGE1 induces multiple actions on the dog heart. Its predominant effect on the ventricular myocardium appears to be enhancement of the adrenergic stimuli probably via the facilitation of calcium movement through the myocardial cell membrane. In addition, PGE1 may decrease the sensitivity of beta-adrenoceptors to adrenergic stimuli in the sinus node.


Ethnic and racial disparities in cardiac resynchronization therapy.
Racial/ethnic differences in the use of cardiac resynchronization therapy with defibrillator (CRT-D) may result from underprovision or overprovision relative to published guidelines. The purpose of this study was to examine the National Cardiovascular Data Registry (NCDR) ICD Registry for ethnic/racial differences in use of CRT-D. We studied white, black, and Hispanic patients who received either an implantable cardioverter-defibrillator (ICD) or CRT-D between January 2005 and April 2007. Two multivariate logistic regression models were fit with the following outcome variables: (1) receipt of either ICD or CRT-D and (2) receipt of CRT-D outside of published guidelines. Of 108,341 registry participants, 22,205 met inclusion criteria for the first analysis and 27,165 met criteria for the second analysis. Multivariate analysis indicated CRT-eligible black (odds ratio [OR] 0.84; 95% confidence interval [CI], 0.75-0.95; P <.004) and Hispanic (OR 0.83; 95% CI, 0.71-0.99; P <.033) patients were less likely to receive CRT-D than were white patients. A substantial proportion of patients received CRT-D outside of published guidelines, although black (OR 1.18; 95% CI, 1.02-1.36; P = .001) and Hispanic (OR 1.17; 95% CI, 1.02-1.36; P = .03) patients were more likely to meet all three eligibility criteria. Black and Hispanic patients who were eligible for CRT-D were less likely to receive therapy compared with white patients. Conversely, in the context of widespread out-of-guideline use of CRT-D, black and Hispanic patients were more likely to meet established criteria. Our findings suggest systematic racial/ethnic differences in the treatment of patients with advanced heart failure.


Partial characterization of an endogenous factor which modulates the effect of catecholamines on synaptosomal Na+, K+-ATPase.
We have previously presented evidence for the existence of a brain soluble factor which mediates the stimulation of synaptosomal ATPases by catecholamines. The stimulation of synaptosomal ATPases by dopamine plus brain soluble fraction was not modified if the soluble fraction was heated for 5 min at 95 degrees C. One day after preparation, the soluble factor inhibited the Na+, K+-ATPase, but not the Mg2+-ATPase activity, and subsequent addition of noradrenaline stimulated the ATPases activities. The inhibitory effect of a 24 h soluble fraction disappeared if the soluble fraction was dialyzed; in this case, noradrenaline did not activate the enzyme activities. Gel filtration in Sephadex G-50 permitted separating a subfraction which inhibited ATPase activity (peak II) from another which stimulated ATPase activity (peak I). Peak I stimulated both Na+, K+, and Mg2+ ATPases. Peak II inhibited only Na+, K+-ATPase, and when stored acidified, it mediated ATPases stimulation by noradrenaline.


Asymptomatic full-term infants born to women with chorioamnionitis may not need routine antibiotics.
While infants with early-onset sepsis require antibiotics, there is little evidence to support their routine use in asymptomatic infants exposed to maternal chorioamnionitis. We aimed to ascertain the incidence of culture-proven sepsis in full-term infants exposed to chorioamnionitis and to determine whether asymptomatic infants need routine antibiotic treatment. This study was retrospective. Included were all full-term infants admitted to our neonatal intensive care unit between 1 January 2017 and 31 May 2018 who were given intravenous antibiotics for maternal chorioamnionitis. After identifying eligible infants, relevant maternal and infant data were collected from our medical records and the Neonatal Intensive Care Units Database. We selected 167 term infants from 7736 deliveries. The incidence of chorioamnionitis was 21 per 1000 deliveries. The mean gestational age was 39 weeks (range 37-41), and 57% infants were male. Asymptomatic infants (76%) received intravenous antibiotics for an average of 2 days compared to 4 days in the symptomatic group (24%), p < 0.001. No infant died or developed culture-positive sepsis. The risk of early-onset sepsis in well-appearing term infants of mothers with chorioamnionitis is low. Further studies are mandatory to determine whether asymptomatic infants of mothers with clinical chorioamnionitis need antibiotic treatment.


There is no relationship between concentration, motility and vacuolated cells.
To determine whether there are differences between concentration and motility in the vacuolated spermatozoa of fertile donors, randomized men and infertile patients, semen samples were compared. Based on the percentages of concentration and motility, samples were divided into three groups: Group I, fertile donors, concentration > 20 x 10(6)/ml, motility > 50%; Group II, patients, concentrations < 20 x 10(6)/ml, motility < 50%; Group III, randomized men, concentration > 20 x 10(6)/ml, motility > 50%. In each group samples were assessed morphologically by the strict criteria of Kruger et al. The results showed that there was no difference between Group I and Group II, but there were differences between Group III and Group II, and Group III and Group I. We conclude that there is no relationship between concentration, motility and vacuolated cells.


Insulin resistance in obesity and metabolic syndrome: is there a connection with platelet l-arginine transport?
Nitric oxide (NO) is a short-lived gaseous messenger with multiple physiological functions including regulation of blood flow, platelet adhesion and aggregation inhibition. NO synthases (NOS) catalyze the conversion of cationic amino acid L-arginine in L-citrulline and NO. Despite an increasing prevalence of obesity and metabolic syndrome (MetS) in the last decades, the exact mechanisms involved in the pathogenesis and cardiovascular complications are not fully understood. We have examined the effects of obesity and MetS on the L-arginine-NO-cGMP pathway in platelets from a population of adolescents. A total of twenty six adolescent patients (13 with obesity and 13 with MetS) and healthy volunteers (n=14) participated in this study. Transport of L-arginine, NO synthase (NOS) activity and cGMP content in platelets were analyzed. Moreover, platelet function, plasma levels of L-arginine, metabolic and clinical markers were investigated in these patients and controls. L-arginine transport (pmol/10(9) cells/min) in platelets via system y(+)L was diminished in obese subjects (20.8±4.7, n=10) and MetS patients (18.4±3.8, n=10) compared to controls (52.3±14.8, n=10). The y(+)L transport system correlated negatively to insulin levels and Homeostasis Model Assessment of Insulin Resistance (HOMA IR) index. No differences in NOS activity and cGMP content were found among the groups. Moreover, plasma levels of L-arginine were not affected by obesity or MetS. Our study provides the first evidence that obesity and MetS lead to a dysfunction of L-arginine influx, which negatively correlates to insulin resistance. These findings could be a premature marker of future cardiovascular complications during adulthood.


Adaptive immune responses in acute and chronic hepatitis C virus infection.
The hepatitis C virus (HCV) persists in the majority of infected individuals and is a significant cause of human illness and death globally. Recent studies have yielded important insights into immunity to HCV, in particular revealing the central role of T cells in viral control and clearance. Other key features of adaptive immune responses remain obscure, including mechanisms by which T cells control HCV replication, the role of antibodies in conferring protection and how cellular and humoral immunity are subverted in persistent infection.


Laparoscopy with left chest collis gastroplasty: a simplified technique for shortened esophagus.
Axial shortening of the esophagus is caused by repetitive esophageal injury from gastroesophageal reflux disease resulting in esophagitis, submucosal fibrosis, and esophageal dysmotility. A short esophagus (<2 cm of intraabdominal length after type II mediastinal dissection) is encountered in 20% to 63% of patients undergoing paraesophageal hernia repair. An esophageal lengthening procedure can be a useful adjunct to fundoplication to reduce the 50% recurrence rate reported at 5 years. We describe a simplified Collis gastroplasty technique that negates the need for wedge fundectomy, potentially saving operating room time and cost, while hypothetically reducing morbidity.


A novel method for cyanide quantification in human whole blood using ion chromatography with amperometric detection and its application to cyanide intoxication cases.
Cyanide is a highly toxic agent that has been frequently used for suicide in South Korea. It is also used in various industrial fields, such as metal plating, in which many accidental cyanide intoxications have occurred. To overcome the disadvantages of conventional cyanide analysis methods, a simple and fast method for the analysis of cyanide in whole blood using ion chromatography (IC) with amperometric detection was developed in this study. Whole blood samples were deproteinized, diluted, and analyzed using an IC-amperometric detection system. The limits of detection and quantitation were 0.1 and 0.2 mg/L, respectively. The method showed good linearity in the range of 0.2 to 50 mg/L with R2 > 0.99. The intra- and inter-assay precision and accuracy values were <10%. The established method was successfully applied to analyze whole blood samples from three cyanide intoxication cases.


Developmental stage affects cognition in children with recently-diagnosed symptomatic focal epilepsy.
This study explored the impact of developmental stage on cognitive function in children with recently-diagnosed epilepsy. In keeping with a neurodevelopmental framework, skills in a critical developmental period were expected to be more vulnerable than those stable at the time of seizure onset. We studied children with early-onset (EO) symptomatic focal epilepsy (onset: 3-5 years; n=18) and compared their performance with that of the group with late-onset (LO) epilepsy (onset: 6-8 years performance of; n=8) on a range of cognitive tasks. Performance of both groups was compared with normative standards. 'Critical' and 'stable' classifications were based on developmental research. Nonparametric analyses revealed that skills in a critical developmental period for the group with EO epilepsy fell below normative standards (Phonological Processing: p=.007, Design Copying: p=.01, Visuomotor Precision:, p=.02) and fell below the performance of the group with LO epilepsy (Design Copying: p=.03, Visuomotor Precision: p=.03). There were no differences between the group with EO epilepsy and the group with LO epilepsy on measures of receptive vocabulary and memory, which were proposed to be in a stable developmental period across both groups. Auditory span, as measured by Word Order, was reduced for both the group with EO epilepsy (p=.02) and the group with LO epilepsy (p=.02) relative to normative standards, but the groups did not differ from each other. These results are consistent with a prolonged period of critical development for this skill. These findings support the notion that skills in a critical phase of development are particularly vulnerable following the onset of symptomatic focal epilepsy in childhood.


Free sterols of the rabbit optic nerve and cerebral white matter during ontogenic development.
Free sterol composition of the developing rabbit optic nerve was compared with that of the homologous cerebral white matter at corresponding stages of ontogeny. The sterols were detected and identified by means of combined gas-chromatography and mass spectrometry. The following free sterols were found in both the optic nerve and cerebral white matter: cholesterol, desmosterol, lanosterol, two dimethylsterols, which are probably 4,4-dimethyl-5 alpha-cholest-8,24-diene-3 beta-ol, with a molecular weight of 412, and 4 alpha, 14 alpha-dimethyl-5 alpha-cholest-7-ene-3 beta-ol, with a molecular weight of 414 and probably cholestene, with a molecular weight of 368. The sterol spectrum of the developing optic nerve differed not only from that of the mature nerve but also from that of age-matched white matter of the rabbit brain. The tri- and dimethyl-sterols, detected for the first time in the rabbit optic nerve and cerebral white matter, are natural components of the developing nervous tissue but they were not found in the mature nerve nor in cerebral white matter.


Initial laboratory predictors of severe hepatitis and acute kidney injury in patients with acute hepatitis A.
The number of adult patients with acute hepatitis A (AH-A) has markedly increased during the last 10 years in Korea. Of special note, an increase in severe complications of AH-A, such as severe liver dysfunction and acute kidney injury (AKI), has emerged as a significant problem. The objective of this study was to identify the initial predictors for development of severe AH-A and AKI in AH-A. We retrospectively reviewed the medical records of 194 patients with AH-A from January 2007 to March 2009. Severe AH-A and AKI developed in 16 (9.3%) and 11 (6.4%) patients, respectively. Independent predictors for severe AH-A were low albumin [odds ratio (OR), 10.91; 95% confidence interval (CI), 2.324-51.215; P=0.002], low total cholesterol (OR, 5.54; 95% CI, 1.389-22.113; P=0.015), and elevated alanine aminotransferase (OR, 20.87; 95% CI, 4.581-95.067; P<0.001). Also, high level of C-reactive protein was independently associated with AKI occurrence in AH-A (OR, 10.91; 95% CI, 2.324-51.215; P=0.002).


Brain MRI features of congenital- and adult-form myotonic dystrophy type 1: case-control study.
To compare and characterize the magnetic resonance imaging (MRI) of brain in the congenital and adult form of myotonic dystrophy type 1, we evaluated five patients with congenital dystrophy type 1, 10 age- and 10 disease duration-matched patients with adult-form dystrophy type 1 and 20 age-matched healthy volunteers. The ventricular enlargement was evaluated by the ventricular:brain ratio, the signal intensity of white matter posterosuperior to trigones by reference to standard images and the white matter lesions by a semiquantitative method. In the congenital dystrophy type 1, MRI was characterized by ventriculomegaly and moderate/severe hyperintensity of white matter posterosuperior to trigones, which showed no correlation with the age. MRI in the adult-form dystrophy type 1 was strictly related to disease duration and varied between normal findings, except for temporo-polar white matter lesions, in age-matched patients and ventriculomegaly with white matter hyperintensities in disease duration-matched patients. These results suggest that the origin of MRI abnormalities in myotonic dystrophy type 1 is mainly developmental for the congenital form and mainly degenerative for the adult form.


Emergent Sasaki-Einstein geometry and AdS/CFT.
A central problem in any quantum theory of gravity is to explain the emergence of the classical spacetime geometry in some limit of a more fundamental, microscopic description of nature. The gauge/gravity-correspondence provides a framework in which this problem can, in principle, be addressed. This is a holographic correspondence which relates a supergravity theory in five-dimensional Anti-deSitter space to a strongly coupled superconformal gauge theory on its 4-dimensional flat Minkowski boundary. In particular, the classical geometry should therefore emerge from some quantum state of the dual gauge theory. Here we confirm this by showing how the classical metric emerges from a canonical state in the dual gauge theory. In particular, we obtain approximations to the Sasaki-Einstein metric underlying the supergravity geometry, in terms of an explicit integral formula involving the canonical quantum state in question. In the special case of toric quiver gauge theories we show that our results can be computationally simplified through a process of tropicalization.


Intracellular pH regulation in isolated fast-twitch skeletal muscle from dystrophin-deficient mouse.
In muscles from anaesthetized dystrophin-deficient mdx mice, exercise results in a stronger acidification and a slower intracellular pH recovery compared to control mice. We examined whether this observation could be attributed to defective H+-carriers in dystrophin-lacking muscles. Immunohistochemistry and Western blots revealed no defect in mdx muscles for the presence of the lactate-/H+co-transporter MCT4 and of the Na+/H+ antiporter NHE1, the main H+-carriers active in fast-twitch skeletal muscle after exercise. Functional tests of the H+-transporters, on isolated muscles submitted to identical flow of superfusion, were performed in conditions meant to lower intracellular pH: repetitive electrical stimulation or NH4Cl pre-pulse. These revealed no defect in intracellular pH recovery in mdx muscles. Therefore, we conclude that impaired intracellular pH regulation in anaesthetized mdx mice is not attributable to a reduced presence or activity of H+-extruders. We propose that CO2 washout might be slowed down in vivo in mdx muscles because of the defective vascular response in contracting muscles from these mice.


Efficacy and safety comparing prasugrel/ticagrelor and clopidogrel in Hong Kong post-acute coronary syndrome patients-A 10-year cohort study.
Clinical evidence of prasugrel/ticagrelor in dual antiplatelet therapy (DAPT) in Asian acute coronary syndrome (ACS) population remains inconclusive. We aimed to compare the clinical efficacy and safety of prasugrel/ticagrelor compared to clopidogrel as part of DAPT in Hong Kong ACS population for 10 years. Prasugrel/ticagrelor, compared to clopidogrel, reduces risk of major adverse cardiovascular event (MACE) in Hong Kong ACS population. The retrospective observational cohort study included patients admitted to seven institutions under Hospital Authority Hong Kong with diagnosis of ACS during 2008-2017. Risk of MACE, defined as composite of cardiovascular (CV) death, non-fatal myocardial infarction (MI) and non-fatal stroke, and risk of any bleeding leading to hospitalization were examined. Baseline characteristics difference was adjusted by propensity score (PS) matching. Adjusted Cox regression model was used to estimate hazard ratio of interested outcome. In PS matched cohort including 944 patients in each group, MACE risk reduction of 40% from 1 year to 5 years after index ACS event was observed in prasugrel/ticagrelor group (HR 0.60, 95% CI 0.39-0.91, p = .015). The risk reduction was highly driven by MI reduction (HR 0.54, 95% CI 0.33-0.91, p = .019). Lower bleeding risk was observed in prasugrel/ticagrelor group compared to clopidogrel from 1 year to 5 years (HR 0.46, 95% CI 0.21-1.00, p = .051). Prasugrel/ticagrelor showed MACE risk reduction over clopidogrel as part of DAPT up to 5 years after index event, while prasugrel/ticagrelor was not associated with increased bleeding risk.


Tailoring metal-organic frameworks-based nanozymes for bacterial theranostics.
Nanozymes are next-generation artificial enzymes having distinguished features such as cost-effective, enhanced surface area, and high stability. However, limited selectivity and moderate activity of nanozymes in the biochemical environment hindered their usage and encouraged researchers to seek alternative catalytic materials. Recently, metal-organic frameworks (MOFs) characterized by distinct crystalline porous structures with large surface area, tunable pores, and uniformly dispersed active sites emerged, that filled the gap between natural enzymes and nanozymes. Moreover, by selecting suitable metal ions and organic linkers, MOFs can be designed for effective bacterial theranostics. In this review, we briefly presented the design and fabrication of MOFs. Then, we demonstrated the applications of MOFs in bacterial theranostics and their safety considerations. Finally, we proposed the major obstacles and opportunities for further development in research on the interface of nanozymes and MOFs. We expect that MOFs based nanozymes with unique physicochemical and intrinsic enzyme-mimicking properties will gain broad interest in both fundamental research and biomedical applications.


Obstetric fistula and sociocultural practices in Hausa community of Northern Nigeria.
Obstetric Fistula is a childbirth injury that disproportionately affects women in sub-Saharan Africa. Although poverty plays an important role in perpetuating obstetric fistula, sociocultural practices has a significant influence on susceptibility to the condition. This paper aims to explore narratives in the literature on obstetric fistula in the context of Hausa ethno-lingual community of Northern Nigeria and the potential role of nurses and midwives in addressing obstetric fistula. Three major cultural practices predispose Hausa women to obstetric fistula: early marriages and early child bearing; unskilled birth attendance and female circumcision and sociocultural constraints to healthcare access for women during childbirth. There is a failure to implement the International rights of the girl child in Nigeria which makes early child marriage persist. The Hausa tradition constrains the decision making power of women for seeking health care during childbirth. In addition, there is a shortage of nurses and midwives to provide healthcare service to women during childbirth. To improve health access for women, there is a need to increase political commitment and budget for health human resource distribution to underserved areas in the Hausa community. There is also a need to advance power and voice of women to resist oppressive traditions and to provide them with empowerment opportunities to improve their social status. The practice of traditional birth attendants can be regulated and the primary health care services strengthened.


GPIbα shedding in platelets is controlled by strict intracellular containment of both enzyme and substrate.
A disintegrin and metalloprotease 17 (ADAM17) catalyzes platelet glycoprotein (GP) Ibα ectodomain shedding, thereby releasing glycocalicin in plasma. The spatiotemporal control over the enzyme-substrate interaction and the biological consequences of GPIbα shedding are poorly understood. This study aimed to determine the spatiotemporal control over GPIbα shedding by ADAM17. Transmission electron microscopy with immunogold staining, immunoprecipitation, and quantitative western blotting were used. Immunogold staining showed that all ADAM17 antigen is expressed intracellularly, irrespective of platelet activation. ADAM17 clustered in patches on a tortuous membrane system different from α- and dense granules. Mild activation by platelet adhesion to immobilized fibrinogen did not cause GPIbα shedding, whereas strong and sustained stimulation using thrombin and collagen (analogs) did. Glycocalicin release kinetics was considerably slower than typical hemostasis, starting at 20 minutes and reaching a plateau after 3 hours of strong stimulation. Inhibition of the ADAM17 scissile bond specifically in GPIbα receptors that reside on the platelet's extracellular surface did not prevent shedding, which is in line with the strict intracellular location of ADAM17. Instead, shedding was restricted to a large GPIbα subpopulation that is inaccessible on resting platelets but becomes partially accessible following platelet stimulation. Furthermore, the data show that proteinaceous, water-soluble ADAM17 inhibitors cannot inhibit GPIbα shedding, whereas membrane permeable small molecule ADAM inhibitors can. The data show that platelets harbor 2 distinct GPIbα subpopulations: one that presents at the platelet's surface known for its role in primary hemostasis and one that provides substrate for proteolysis by ADAM17 with kinetics that suggest a role beyond hemostasis.


Incidentally Detected Subclinical Limbic Encephalitis on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in a Patient with Myasthenia Gravis and Sarcoidosis: A Rare Immunological Triad?
Limbic encephalitis is the inflammation of the medial temporal lobe structures due to direct infectious or indirect autoimmune etiology. Sarcoidosis is a rare cause of limbic encephalitis, has been reported by some authors. Association has also been reported between sarcoidosis, myasthenia gravis, and limbic encephalitis. We report an interesting case of 18F-fluorodeoxyglucose positron emission tomography/computed tomography demonstrating limbic encephalitis and sarcoidosis in a known case of myasthenia gravis.


Nanoliposomes increases Anti-Trichomonas vaginalis and apoptotic activities of metronidazole.
Trichomoniasis, caused by Trichomonas vaginalis (T. vaginalis), is the most common non-viral sexually transmitted disease worldwide. As current trichomoniasis chemotherapies have many side effects, we examined the Anti-Trichomonas effects of nano-liposomal metronidazole (NLMTZ) compared to metronidazole (MTZ) in vitro. Liposomes were produced using the thin film hydration-sonication technique with a slight modification coated with MTZ. The average hydrodynamic diameter of monodispersed NLMTZ was evaluated by DLS and the morphological measurements were performed by scanning electron microscopy (SEM). The effects of NLMTZ and MTZ (5, 10, 20 and 40 µg/mL) on T. vaginalis trophozoites (105 cells/mL) in trypticase-yeast extract-maltose (TYM) medium were evaluated in different exposure times. Then, cell viability, IC50, SEM analysis and the expression of the metacaspase gene were assessed by qRT-PCR. Growth inhibition of MTZ in a concentration of 40 μg/mL was 39.34% after 3 h, whereas NLMTZ caused 51% growth inhibition after 3 h and lysed Trichomonas completely after 12 h. The IC50 values were estimated at 31.51 and 15.90 μg/mL after a 6 h exposure for MTZ and NLMTZ, respectively. Moreover, both T. vaginalis treated with MTZ and NLMTZ had high levels of metacaspase mRNA expression relative to the control groups (P< 0.05). A significant difference was observed between the apoptotic intensities of T. vaginalis treated with MTZ and NLMTZ (P< 0.05). This study showed that nano-liposomal MTZ is a potentially excellent approach for the treatment of trichomoniasis in vitro, although further studies are needed before consideration of clinical trials.


Effects of prostaglandin E2, forskolin and cholera toxin on cAMP production and in vitro LH-RH release from the rat hypothalamus.
The present study attempts to elucidate the possible role of adenosine 3',5'-monophosphate (cAMP) and prostaglandin E2 (PGE2) in the function of the neural luteinizing hormone-releasing hormone (LH-RH) apparatus. To this end, in vitro LH-RH release from superfused hypothalamic fragments and cAMP production by hypothalamic P2 membrane fractions were measured. Immature female rats (day 28) were ovariectomized and implanted with Silastic capsules containing estradiol (235 micrograms/ml). Two days later, animals were sacrificed and the mediobasal hypothalamic preoptic area (hypothalamic units or fragments) were removed. To examine in vitro LH-RH release from superfused hypothalamic fragments, effluents were collected into tubes on ice at 10-min intervals and LH-RH concentration was determined by radioimmunoassay (RIA). Following a 50-min control period, a step-wise increment in several doses of PGE2 (each dose for a 50-min interval) evoked a dose-related increase in LH-RH release. PGE2 induced significant (P less than 0.01) increments in LH-RH release at doses of 5.68 X 10(-7), 5.68 X 10(-6), and 5.68 X 10(-5) M, respectively. When adenylate cyclase activators, such as forskolin and cholera toxin were infused in a step-wise manner (each dose for a 50-min interval) following a 50-min control period, a dose-related increase in LH-RH release was also obtained; forskolin and cholera toxin significantly (P less than 0.01) stimulated LH-RH release at doses of 1 X 10(-4) and 5.4 X 10(-10) M, respectively. These two substances were ineffective in stimulating LH-RH release when hypothalamic fragments were superfused in calcium-free plus EGTA (10 mM) containing medium.(ABSTRACT TRUNCATED AT 250 WORDS)


A novel method to purify adenovirus based on increasing salt concentrations in buffer.
With the rapid development of gene therapy, gene-based medicine with adenovirus as vectors has become a new method for disease treatment. However, there are still enormous challenges in the large-scale production of adenoviruses for clinical use. Recent reports show that ion-exchange chromatography (IEC) is an effective tool for the isolation and purification of adenovirus. However, during the separation and purification, host cell protein and DNA, as well as serum from the culture medium, can non-specifically occupy numerous binding sites of the chromatography packings, thereby reducing the binding between the adenovirus and packing media. We here report a novel method for highly efficient purification of adenoviruses by increasing the salt concentrations of the samples to be ultrafiltrated by tangential flow filtration, the diafiltration buffer, and the samples for IEC purification. This method could significantly remove a large amount of serum proteins and host cell proteins, increase the amount of sample loaded on the IEC column, and improve the binding of the adenovirus samples to the packing media. A purity of > 95% could be obtained after one chromatography operation, and the number of purification steps and the amount of used packing media were reduced. The method is simple, economical, and efficient, and has excellent applications.


Pulmonary infection in patients with severe fever with thrombocytopenia syndrome: A multicentre observational study.
Co-infection in patients with severe fever with thrombocytopenia syndrome (SFTS) has been reported, posing a serious threat to survival and treatment. We aimed to systematically investigate the SFTS associated pulmonary infection, particularly invasive pulmonary fungal infection (IPFI). During April 2019 to October 2021, we conducted a multicentre observational study on adult hospitalized patients confirmed with SFTS from three tertiary hospital in central China. Demographic, clinical and laboratory data of patients were collected and re-assessed. A total of 443 patients (51.7% were male sex) were included for analysis with median age of 65-year-old. Among them, 190 (42.9%) patients met the criteria for pulmonary infection. Pulmonary infection was associated with shorter survival time (p < 0.0001 by log-rank test), and adjusted hazard ratio was 1.729 [95% confidence interval, 1.076-2.780] (p = 0.024). Age (odds ratio (OR) 1.040 [1.019-1.062], p < 0.001), time from onset to admission (OR 1.163 [1.070-1.264], p < 0.001), having severe status (OR 3.166 [2.020-4.962], p < 0.001) and symptoms of skin change (OR 2.361 [1.049-5.316], p < 0.001) at admission and receiving intravenous immunoglobin (OR 2.185 [1.337-3.569], p = 0.002) were independent risk factors for the occurrence of pulmonary infection. A total of 70 (15.8%) patients were defined as IPFI. Multivariate analysis showed that time from onset to admission (OR 1.117 [1.016-1.229], p = 0.022), severe status (OR 5.737 [3.054-10.779], p < 0.001), having smoking history (OR 3.178 [1.251-8.070], p = 0.015) and autoimmunity disease (OR 7.855 [1.632-37.796], p = 0.010), receiving intravenous immunoglobin (OR 3.270 [1.424-7.508], p = 0.005) were independent risk factors for the occurrence of IPFI. In SFTS patients with pulmonary infection, white blood count <2.09 × 109 per L (OR 11.064 [3.708-33.012], p < 0.001) and CD3+ CD4+ T cell count <104.0 per μL (OR 10.429 [3.395-32.038], p < 0.001) could independently predict IPFI. This study showed the high prevalence and poor outcomes of pulmonary infection and IPFI in patients with SFTS. These findings highlighted the need for active surveillance of fungal pathogens and early antifungal treatment in patients with SFTS.


Involvement of histamine 1 receptor in seizure susceptibility and neuroprotection in immature mice.
The central histaminergic neuronal system is a powerful modulator of brain activity, and its functional disturbance is related to e.g. epilepsy. We have recently shown in the slice culture system that histaminergic neurons attenuate kainic acid (KA)-induced epileptiform activity and neuronal damage in the hippocampus through histamine 1 (H1) receptors. We now further examined the role of H1 receptors in the regulation of KA-induced seizures and neuronal damage in immature 9-day-old H1 receptor knock out (KO) mice. In the H1 receptor KO mice, behavioral seizures were significantly more severe and duration of seizures was significantly longer when compared to the wild type (WT) mice at the KA dose of 2mg/kg. Moreover, neuronal damage correlated with seizure severity, and it was significantly increased in the thalamus and retrosplenial granular cortex (RGC) of the KO mice. The H1 receptor antagonist triprolidine treatment supported these findings by showing significantly increased seizures severity and neuronal damage in the septum, thalamus, CA3 region of the hippocampus, and RGC in the KA-treated WT mice. Our present novel findings suggest that H1 receptors play a pivotal role in the regulation of seizure intensity and duration as well as seizure-induced neuronal damage in the immature P9 mice.


Clinical experience with the Palmaz-Schatz coronary stent.
Complications that occurred in 247 patients who underwent successful elective stenting to native coronary arteries with the Palmaz-Schatz balloon expandable stent included subacute thrombosis in 7 patients (2.8%), myocardial infarction in 3 (1.2%), death 3 (1.2%), urgent bypass surgery in 4 (1.6%) and major bleeding events in 24 (9.7%). Angiographic restenosis occurred in 21 (20%) of 103 patients who received a single stent. Subgroup analysis, however, revealed that restenosis of a single stent occurred in 3 (7%) of 45 patients without prior angioplasty compared with 25 (27%) of 91 patients with prior angioplasty. Patients with "suboptimal" angioplasty results (dis-section) who received a single stent seemed to have a higher thrombosis rate perioperatively (4 [4%] of 98), but no higher incidence of restenosis (7 [15%] of 46) than that of the total group of patients who received a single stent. Coronary stenting may be a valuable adjunct to coronary angioplasty in carefully selected patients. Complication rates are similar to those of routine angioplasty; however, angiographic restenosis may be reduced in certain subsets of patients.


Understanding the impact of socioeconomic differences in breast cancer survival in England and Wales: avoidable deaths and potential gain in expectation of life.
Socioeconomic differences in cancer patient survival are known to exist for women diagnosed with breast cancer. Standard metrics tend not to place great emphasis on evaluating the actual impact of these differences. We used two alternative, but related, methods of reporting the impact of socioeconomic differences for breast cancer patients in England and Wales. We calculated the average gain in life years for each patient should socioeconomic differences in relative survival be removed and show how this is related to the number of all-cause deaths that could be postponed by removing socioeconomic differences in cancer patient survival. Our results indicate that deprivation differences for women with breast cancer exist and result in women from more deprived areas losing a larger proportion of their life due to a diagnosis of cancer. We also estimate that on average 1.1 years could be gained for a 60 year old breast cancer patient in the most deprived group by improving their relative survival to match the least deprived group. However, our results also show that deprivation differences in general survival have a large impact on life expectancy; showing that over two-thirds of the gap in differential life expectancy is explained by differences in other-cause survival. Socioeconomic differences in relative survival have an impact on life expectancy for patients and result in higher early mortality for more deprived patients. However, differences in general survival across socioeconomic groups explain a larger proportion of the deprivation gap in life expectancy for breast cancer patients.


Molecular cloning and characterization of Borrelia burgdorferi rpoB.
Borrelia burgdorferi rpoB, the gene encoding the beta-subunit of RNA polymerase, has been cloned and sequenced. The full-length gene encodes a protein of 1154 amino acids with a calculated molecular mass of 129.8 kDa. The amino-acid sequence is 49% identical to the corresponding protein from Escherichia coli. B. burgdorferi rpoB is a component of a gene cluster, which includes rplJ, rplL and rpoC. A temperature-sensitive E. coli rpoB mutant could be complemented by introduction of the B. burgdorferi gene, indicating that the B. burgdorferi rpoB is expressed in E. coli and the beta-subunit can be assembled into functional holoenzyme. The wild-type amino-acid sequence of the B. burgdorferi beta-subunit is consistent with those of spontaneously arising rifampicin-resistant mutants of E. coli and Mycobacterium tuberculosis at certain critical residues. This suggests that the natural resistance of B. burgdorferi to rifampicin may be due to the primary amino-acid sequence of its beta-subunit.


Harmonics, evolutionary generators, DANCE, and HEAR-functional dimensions.
Evolution of the major kingdoms of life has spanned over the last 4 billion years on Earth. Studies of the process comprise different fields of study with alternative perspectives. This paper focuses on mathematic unification of the subject area; enriching an engineering based structure to advance our understanding of pathways which lead to distinct constructs in life, furthering geographic bordering processes with biological context. Application of logistic regression requires partitioning of variance within cellular and molecular systems; use of higher mathematic technique (multi-objective genetic algorithm) generates variance within the different scales of evolution, the result of which is analogous with the Fisher equation model of gene distribution within populations. Laboratory and field studies were integrated to illustrate emergence in evolutionary processes in the terrestrial/soil environment. Nematological field and laboratory trials validate the existence of triangular relationships within biological communities; further harmonic constants between interacting species may be found with emergent consequence. We distinguish different strategical groupings in the soil community, with the core groupings recognized with Meloidogyne spp. illustrating positive (emergent) growth; Radopholus similis (neutral growth), and Helicotylenchus pseudorobustus (negative growth). The patterns of emergent systems are shown in the extremes of Morocco's dynamic soil environment. Fuzzy classification methods: Mamdani, Takugi-Sugeno-Kang; additional novel DANCE (Differential Algorithmic Network Centered Emergence) and functional expressions HEAR (Harmonic Evolutionary Algorithmic Resilience), are recommended to give a basis for development of constructs covering different categories of life.


Pseudoangiomatous Stromal Hyperplasia of Breast in an Adolescent: A Case Report and Review of the Literature.
Pseudoangiomatous stromal hyperplasia (PASH) is a rare benign breast lesion that is is extremely rare in children and adolescents. A 13-year-old girl was admitted to our clinic with a giant mass in the left breast for 3 months. Physical examination findings of the patient were normal except for the mass in the breast. The mass was removed totally, and its pathological diagnosis was pseudoangiomatous stromal hyperplasia. The patient has been followed up for 6 months without disease.


[Control of the level of human chorionic gonadotropin in urine compared to the level of serum after medically provoked abortion is a safe alternative].
Medical abortion with combined mifepristone and misoprostol is a highly effective, safe, and widely used method for medical termination of pregnancy. In this review, it is shown that self-testing with a urine human chorionic gonadotropin stix (detection limit greater than 25 IU/l) four weeks after administration of medication is a safe, practical, and cheap method to determine successful termination.


Amino acid transport in isolated rat thymocytes. Effects of divalent cations and ethanol.
In dispersed rat thymocytes neither basal alpha-aminoisobutyric acid influx nor influx stimulated by insulin, prostaglandin theophylline, or butyryl adenosine 3':5'-monophosphate (cyclic AMP) depended on extracellular calcium or magnesium. The divalent cation ionophore A23187 inhibited both basal and stimulated alpha-aminoisobutyric acid influx. The extent to which influx was inhibited depended on ionophore concentration, extracellular calcium concentration, and time but did not depend on extracellular magnesium. Significant inhibition could be detected at an ionophore concentration of 1 muM and maximal inhibition occurred with 6 muM A23187. A23187 increased cellular uptake of calcium and there was good agred calcium uptake and that for ionophore inhibition of alpha-aminoisobutyric acid influx. Incubating cells with A23187 and then adding ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N',-tetraacetic acid completely reversed ionophore-stimulated cellular calcum uptake but did not reverse inhibition of alpha-aminoisobutyric acid influx. Thus, A23187 produces irreversible inhibition of alpha-aminoisobutyric acid transport in dispersed rat thymocytes. Ethanol abolished insulin-stimulated alpha-aminoisobutyric acid influx but did not alter basal influx or that stimulated by prostaglandin E1, theophylline, or N6,O2'-dibutyryl adenosine 3':5'-monophosphate. Inhibition could be detected with 0.2% (v/v) ethanol and insulin-stimulated alpha-aminoisobutyric influx was abolished with 1% ethanol. The effect of ethanol occurred immediately and could be reversed completely. This ability of ethanol to inhibit selectively insulin-stimulated alpha-aminoisobutyric acid influx indicates that the mechanism through which insulin stimulates alpha-aminoisobutyric acid influx is functionally distinct from the stimulation produced by cyclic AMP.


Identification and computational analysis of mutations in SARS-CoV-2.
SARS-CoV-2 infection has become a worldwide pandemic and is spreading rapidly to people across the globe. To combat the situation, vaccine design is the essential solution. Mutation in the virus genome plays an important role in limiting the working life of a vaccine. In this study, we have identified several mutated clusters in the structural proteins of the virus through our novel 2D Polar plot and qR characterization descriptor. We have also studied several biochemical properties of the proteins to explore the dynamics of evolution of these mutations. This study would be helpful to understand further new mutations in the virus and would facilitate the process of designing a sustainable vaccine against the deadly virus.


Mechanical factors in the initiation and propagation of tears of the rotator cuff. Quantification of strains of the supraspinatus tendon in vitro.
Differential strain has been proposed to be a causative factor in failure of the supraspinatus tendon. We quantified the strains on the joint and bursal sides of the supraspinatus tendon with increasing load (20 to 200 N) and during 120 degrees of glenohumeral abduction with a constant tensile load (20 to 100 N). We tested ten fresh frozen cadaver shoulders on a purpose-built rig. Differential variable reluctance extensometers allowed calculation of the strain. Static loading to 100 N or more increased strains on the joint side significantly more than on the bursal side. During glenohumeral abduction an increasing and significant difference in strain was measured between the joint and bursal sides of the supraspinatus tendon, which reached a maximum of 10.6% at abduction of 120 degrees. The joint side strain of 7.5% reached values which were previously reported to cause failure. Differential strain causes shearing between the layers of the supraspinatus tendon, which may contribute to the propagation of intratendinous defects that are initiated by high joint side strains.


Gold supported on a mesoporous CeO2 matrix as an efficient catalyst in the selective aerobic oxidation of aldehydes in the liquid phase.
Gold supported on CeO2 catalyses the selective aerobic oxidation of aliphatic and aromatic aldehydes better than other reported catalysts such as Pt/C/Bi materials; the activity is due to the nanometric particle size of Au and CeO2.


Linolenic acid deficiency.
Linolenic acid deficiency has not been demonstrated clearly in warm blooded animals, yet circumstantial evidence suggests that n-3 fatty acids may have functions in these animals. The fact that several species of fish definitely require dietary n-3 fatty acids indicates that n-3 fatty acids have important and specific functions in these animals and suggests that such functions may also be present in warm blooded animals. It is also true that n-3 fatty acid distribution in tissues of birds and mammals appears to be under strict metabolic control, and that this complex metabolic control mechanism apparently has survived evolutionary pressure for a very long time. So far, attempts to produce linolenic acid deficiency in mammals have not revealed an absolute requirement for n-3 fatty acids. If functions for n-3 fatty acids do exist in warm blooded animals, it seems probable that they may be located in the cerebral cortex or in the retina, because these tissues normally contain high concentrations of n-3 fatty acids.


Immune profiling by multiple gene expression analysis in patients at-risk and with type 1 diabetes.
There is a need for biomarkers to monitor the development and progression of type 1 DM. We analyzed mRNA expression levels for granzyme B, perforin, fas ligand, TNF-α, IFN-γ, Foxp3, IL-10, TGF-β, IL-4, IL-6, IL-17, Activation-induced cytidine deaminase (AID) and Immunoglobulin G gamma chain (IgG<gamma>) genes in peripheral blood of at-risk, new-onset and long-term type 1 DM , and healthy controls. The majority of the genes were suppressed in long-term type 1 DM compared to controls and new-onset patients. IFN-γ, IL-4 and IL-10 mRNA levels were significantly higher in new-onset compared to at-risk and long-term groups. There was decreased mRNA expression for AID and IgG<gamma> and up-regulation of IFN-γ with age in controls. Data suggest an overall depressed immunity in long-term type 1 DM. Increased gene expression levels for IFN-γ, IL-4 and IL-10 in new-onset patients from at-risk patients might be used as potential markers for progression of the disease.


One-step finite-difference time-domain algorithm to solve the Maxwell equations.
We present a one-step algorithm to solve the time-dependent Maxwell equations for systems with spatially varying permittivity and permeability. We compare the results of this algorithm with those obtained from the Yee algorithm and from unconditionally stable algorithms. We demonstrate that for a range of applications the one-step algorithm may be orders of magnitude more efficient than multiple time-step, finite-difference time-domain algorithms. We discuss both the virtues and limitations of this one-step approach.


Hematopoietic Fas deficiency does not affect experimental atherosclerotic lesion formation despite inducing a proatherogenic state.
The Fas death receptor (CD95) is expressed on macrophages, smooth muscle cells, and T cells within atherosclerotic lesions. Given the dual roles of Fas in both apoptotic and nonapoptotic signaling, the aim of the present study was to test the effect of hematopoietic Fas deficiency on experimental atherosclerosis in low-density lipoprotein receptor-null mice (Ldlr(-/-)). Bone marrow from Fas(-/-) mice was used to reconstitute irradiated Ldlr(-/-) mice as a model for atherosclerosis. After 16 weeks on an 0.5% cholesterol diet, no differences were noted in brachiocephalic artery lesion size, cellularity, or vessel wall apoptosis. However, Ldlr(-/-) mice reconstituted with Fas(-/-) hematopoietic cells had elevated hyperlipidemia [80% increase, relative to wild-type (WT) controls; P < 0.001] and showed marked elevation of plasma levels of CXCL1/KC, CCL2/MCP-1, IL-6, IL-10, IL-12 subunit p70, and soluble Fas ligand (P < 0.01), as well as systemic microvascular inflammation. It was not possible to assess later stages of atherosclerosis because of increased mortality in Fas(-/-) bone marrow recipients. Our data indicate that hematopoietic Fas deficiency does not affect early atherosclerotic lesion development in Ldlr(-/-) mice.


Twelve weeks of sprint interval training increases peak cardiac output in previously untrained individuals.
Sprint interval training (SIT), characterized by brief bouts of 'supramaximal' exercise interspersed with recovery periods, increases peak oxygen uptake ([Formula: see text]) despite a low total exercise volume. Per the Fick principle, increased [Formula: see text] is attributable to increased peak cardiac output ([Formula: see text]) and/or peak arterio-venous oxygen difference (a-vO2diff). There are limited and equivocal data regarding the physiological basis for SIT-induced increases in [Formula: see text], with most studies lasting ≤ 6 weeks. To determine the effect of 12 weeks of SIT on [Formula: see text], measured using inert gas rebreathing, and the relationship between changes in [Formula: see text] and [Formula: see text]. 15 healthy untrained adults [6 males, 9 females; 21 ± 2 y (mean ± SD)] performed 28 ± 3 training sessions. Each session involved a 2-min warm-up at 50 W, 3 × 20-s 'all-out' cycling bouts (581 ± 221 W) interspersed with 2-min of recovery, and a 3-min cool-down at 50 W. Measurements performed before and after training showed that 12 weeks of SIT increased [Formula: see text] (17.0 ± 3.7 vs 18.1 ± 4.6 L/min, p = 0.01, partial η2 = 0.28) and [Formula: see text] (2.63 ± 0.78 vs 3.18 ± 1.1 L/min, p < 0.01, partial η2 = 0.58). The changes in these two variables were correlated (r2 = 0.46, p < 0.01). Calculated peak a-vO2diff also increased after training (154 ± 22 vs 174 ± 23 ml O2/L; p < 0.01) and was correlated with the change in [Formula: see text] (r2 = 0.33, p = 0.03). Exploratory analyses revealed an interaction (p < 0.01) such that [Formula: see text] increased in male (+ 10%, p < 0.01) but not female participants (+ 0.6%, p = 0.96), suggesting potential sex-specific differences. Twelve weeks of SIT increased [Formula: see text] by 6% in previously untrained participants and the change was correlated with the larger 21% increase in [Formula: see text].


Essential oils as an effective alternative for the treatment of COVID-19: Molecular interaction analysis of protease (Mpro) with pharmacokinetics and toxicological properties.
The current health concern to the entire world is the chronic respiratory disease caused by coronavirus 2 (COVID-19). A specific treatment or proper therapy is still lacking, and the investigations from across the world for proper drug/vaccine development towards disease control are in progress. The Coronavirus replication takes place by the conversion of the polypeptide into functional protein and this occurs due to the key enzyme Main protease (Mpro). Therefore, identification of natural and effective Mpro inhibitors could be a safe and promising approach for COVID-19 control. The present in silico study evaluates the effect of bioactive compounds found in Eucalyptus and Corymbia species essential oil on Mpro by docking. Molecular docking of the major seven compounds of essential oil (citronellol, alpha-terpineol, eucalyptol, d-limonene, 3-carene, o-cymene, and alpha-pinene) with Mpro was studied by AutoDock 4.2, and the properties were analysed by PreADMET and Biovia Discovery Studio visualizer. The calculated parameters such as binding energy, hydrophobic interactions, and hydrogen bond interactions of 6LU7 (Mpro) with Eucalyptus and Corymbia volatile secondary metabolites represented its scope as an effective therapy option against covid-19. Among the docked compounds, eucalyptol shows the least binding energy without toxicity. The outcome of this study reported that the essential oil of Eucalyptus and Corymbia species, mainly eucalyptol can be utilized as a potential inhibitor against COVID-19 and also it can be used in its treatment. Hence, further analysis was required to explore its potential application in medicine.


A primary adenocarcinoma of the transverse colon mimicking Crohn's disease: a case report and literature review.
Diarrhoea and weight loss are presenting features of both Crohn's disease and colorectal cancer; however, the two conditions can usually be distinguished on the basis of characteristic patterns of abnormalities observed at the time of initial blood testing and imaging. In patients with suspected Crohn's disease these are often considered sufficient grounds to commence empirical treatment before the results of histology are available. This case report describes a 45-year-old man whose initial clinical, endoscopic and radiological investigations were strongly suggestive of a diagnosis of Crohn's disease, but who subsequently was found to have an adenocarcinoma of the mid-transverse colon. He went on to have an emergency extended right hemi-colectomy.


IL-10 is predominantly produced by CD19(low)CD5(+) regulatory B cell subpopulation: characterisation of CD19 (high) and CD19(low) subpopulations of CD5(+) B cells.
IL-10 production by CD19(+)CD5(+) B cells was investigated, by determining the expression levels of CD19, a classical B cell marker. Peripheral mononuclear cells were stained with fluorescence-conjugated anti-CD5, anti-CD19, anti-IL-10, and Annexin V. Interestingly, IL-10-producing B cells were found to be localised within the CD19(low)CD5(+) B cell subset. Apoptotic changes were also observed mainly in CD19(low) cells among B cells. Thus, CD5(+) B cells should be classified as CD19(high) and CD19(low) cells, and the immunological significance of CD19 for the IL-10 production by CD5(+) B cells requires further studies.


Interaction between mutations of ribosomes and RNA polymerase: a pair of strA and rif mutants individually temperature-insensitive but temperature-sensitive in combination.
A temperature-sensitive lethal mutant of Escherichia coli has been constructed by combining two temperature-insensitive mutations: a rif180 mutation that modifies RNA polymerase (RNA nucleotidyltransferase; nucleosidetriphosphate:RNA nucleotidyltransferase, EC 18.104.22.168) and a strA24 mutation that modifies the ribosomal protein S12. The temperature sensitivity is a property of the combination of these two particular alleles; replacement of either of the alleles relieves the temperature sensitivity. An isogenic strain containing a different strA mutation (i.e., rif180 strA11) is not temperature sensitive. Evidently ribosomes modified by the particular strA24 polymerase altered by the rif180 mutation, which suggests that in vivo there may exist some interaction between structures of ribosomes and the RNA polymerase.


The new Code of Ethics of the World Psychiatric Association: A fresh look at the ethical issues of the psychiatric profession.
This article develops the WPA's new Code of Ethics that was developed in 2020. It succeeds the Declaration of Hawaii of 1977 and the Declaration of Madrid of 1996. The Code is divided into four sections that cover the practice of psychiatry in clinical practice, education, research and publication as well as public mental health. We will discuss the new ethical issues that this Code raises in parallel with the development of psychiatry and psychiatrists' role in society in recent years.


Maternal rejection and children's intensity. Implications for sex differences in affective development.
The interaction between intensity and activity of children and their mothers' rejective attitude is studied. It appears that hostile mothers fault their daughters for their intensity in a much more direct manner than their sons. It is suggested that this differential attitude is of consequence in the development of women and men in our society.


I Wear a Mask for My Country: Conspiracy Theories, Nationalism, and Intention to Adopt Covid-19 Prevention Behaviors at the Later Stage of Pandemic Control in China.
Various conspiracy theories have accompanied COVID-19 since its initial outbreak. Based on a nationwide survey in China, this study probes the health consequences of beliefs in different COVID-19 conspiracy theories in China. The research found that believing the coronavirus has a foreign natural origin was associated with increased rather than decreased intention to adopt protective behaviors. Nonetheless, believing that the source of the pandemic was a Chinese lab or that it is a foreign biological weapon was related to reduced intentions to protect one's health. In addition, measured as national pride and satisfaction with China's pandemic control effort, people's level of nationalism was strongly associated with their intention to adopt protective behaviors, which moderates the health consequences of believing in false conspiracy theories. Scientific literacy was also associated with an increased likelihood of adopting preventive measures. Despite revealing the diversified health consequences of conspiracy beliefs, this study demonstrates the importance of examining collectivist sociopolitical constructs in health communication.


Interactions of dietary insulin index and dietary insulin load with brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in relation to cardiometabolic markers in Iranian diabetic patients: a cross-sectional study.
The progression of cardiometabolic diseases is determined by both genetic and environmental factors. Gene-diet interactions may therefore be important in modulating the risks of developing metabolic diseases. The objectives were to investigate the effect of the interaction between brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms and dietary insulin index (DII) and dietary insulin load (DIL) on cardiometabolic markers among diabetic patients. In this cross-sectional study, blood samples were collected from 667 patients. DIL and DII were defined using a validated FFQ. Genotyping the BDNF Val66Met polymorphism was conducted by the PCR-Restriction fragment length polymorphism (RFLP) method. Interactions between dietary indices and gene variants were evaluated using a generalised linear model. PGF2a concentrations were significantly higher among Val homozygotes than Met-allele carrier. This study revealed that, compared with individuals with the Val/Val genotype, those with the Met/Val or Met/Met genotype had lower BMI (Pinteraction = 0·04), TAG (Pinteraction = 0·04), leptin (Pinteraction = 0·01), LDL (Pinteraction = 0·04) and total cholesterol (Pinteraction = 0·01) when they consumed diets higher on the DIL index. Moreover, the highest quartile of the DIL, compared with the lowest, showed increase in waist circumference (Pinteraction = 0·02) and LDL/HDL (Pinteraction = 0·04) for Val/Val homozygotes compared with Met-allele carriers. BDNF Val66Met variants may interact with DIL and DII, thus be involved in the development of cardiometabolic risk factors. If diabetic patients with Met alleles regulate dietary intakes, they have a protective opportunity to regulate their cardiometabolic markers.


The workplace quality of life of university hospital digestive surgeons: Results of a 2019 nationwide survey.
Burnout syndrome (BOS) affects all professional categories, particularly in the medical sector. Perceived deterioration of working conditions in university hospital centres impacts not only hospital doctors, but also and more generally, university hospital (UH) staff. The goal of this survey was to analyse workplace quality of life among French UH digestive surgeons. An online questionnaire was addressed to all members of sub-section 52-02 (digestive and visceral surgery) of the national university council (CNU). It contained isolated questions, as well as the specific Copenhagen Burnout Inventory (CBI) questionnaire, which assesses three fields: personal burnout (PBO), work-related burnout (WBO) and client-related burnout (CBO). While 132 (85%) out of the 156 surgeons responded, only 110 (70%) filled out the CBI questionnaire. Their perceptions of quality of life were poor or very poor (57%), and progressively poorer; this was mainly due to a lack of human, logistical and financial means, and also to conflictual relations with administration. The CBI questionnaire showed high scores for PBO (37%) and WBO (30%), with lower scores for CBO (8%). Depressive syndrome appeared among 26% of respondents. There were no significant differences according to region, gender or age. This study objectifies a perceived deterioration of the working conditions of UH digestive surgeons, with elevated rates of BOS and a depressive risk superior to that of the overall population.


Detection of anabolic androgenic steroids in serum samples.
When testing for anabolic androgenic steroids (AAS) outside sports communities, for example, in healthcare and forensic medicine, urine is the matrix of choice. However, there are drawbacks with urinary sampling, and serum might be useful as a complementary matrix. The aim was to develop an LC-MS/MS method for serum measuring AAS frequently used outside of sport, including testosterone (T), steroid esters, and eight other synthetic AAS. The sample pretreatment included sample precipitation and evaporation. Limit of quantification for the AAS was 0.05-0.5 ng/mL, and linearity was 0.05-20 ng/mL for most of the substances. Generally, the within- and between-day CV results, matrix effect, and process efficiency were <15%. The AAS were stable for at least 6 months at -20°C. Serum samples were obtained from previous studies. A novel finding from an administration study was that T enanthate was present in serum even after 5 years of storage at -20°C. Serum samples from self-reporting AAS individuals, where T esters were detected, were positive for testosterone using the urinary testosterone/epitestosterone criterion >10. Of those identified as positive in traditional urinary doping tests (n = 15), AAS in serum were found in 80% of the subjects. Our results show that serum may be a valid complementary matrix to urine samples for AAS testing.


Noninvasive Detection of iC3b/C3d Deposits in the Kidney Using a Novel Bioluminescent Imaging Probe.
Histologic quantification of complement C3 deposits in kidney biopsies provides prognostic information in patients with glomerulonephritis. Unfortunately, kidney biopsies are invasive procedures that cannot be performed regularly and only provide a snapshot of a small portion of one kidney at the time of sampling. We have developed a method to noninvasively detect specific C3 fragment deposition throughout both kidneys, using a monoclonal antibody targeting tissue-bound iC3b/C3d linked to a bioluminescent resonance energy transfer construct that emits near-infrared light. In a mouse model of glomerulonephritis, the probe detected iC3b/C3d in kidneys of live mice by bioluminescent imaging. This demonstrates that noninvasive imaging with an anti-iC3b/C3d probe can be used to monitor inflammation in the kidneys.


Extensive abdominal surgery and scar does not absolutely contraindicate bilateral flap harvest from the abdomen: A case report.
This case reports a female patient with a history of multiple laparotomies including stoma formations and reversals, who underwent successful bilateral abdominal flap based breast reconstruction. It highlights that even complex and repeated abdominal surgery is not an absolute contraindication to this procedure. A 52-year-old female with a history of bilateral mastectomy and implant-based breast reconstruction presented with bilateral capsular contracture, wanting removal and alternative breast reconstruction. Her history of ulcerative colitis and multiple complex and extensive abdominal surgeries initially seemed to preclude bilateral abdominal flap harvest and the patient was referred on for another opinion. CT-angiography after the subsequent opinion identified adequate deep inferior epigastric artery perforators and successful bilateral abdomen-based flap reconstruction was performed. This is the first case report of successful bilateral abdomen-based flap harvest in a patient with 6 previous laparotomies including stoma formations and reversals. Complex and extensive abdominal surgery is not an absolute contraindication to bilateral flap harvest from the abdomen. With accurate CT-angiography to guide pre-operative planning and meticulous surgery, safe flap harvest is possible.


Cycling of redox-sensitive trace metals in barrier island freshwater lenses.
Freshwater lenses connect the terrestrial and marine realm via groundwater discharge at the edges of islands and serve as drinking water resources. We studied the redox-sensitive metals U, Mo, V, and Tl along the redox gradient of fresh groundwater lenses on Spiekeroog Island, northern Germany. Groundwater solute concentrations were linked to groundwater age and redox characteristics. We further quantified the contribution of precipitation, sea spray, and aquifer matrix to the groundwater metal concentrations and evaluated the sink and source function of the aquifer under oxic and reducing conditions. We found that biogeochemical processes altered the concentrations of the trace metals. In young, oxygen to nitrate reducing zones, the aquifer matrix represented the major metal source to the groundwater. For Tl, rain was an additional important (anthropogenic) source. Under manganese and iron oxide to sulfate reducing conditions, U and Tl were sensitive to redox dependent removal, whereas Mo and V were less affected by reductive precipitation/adsorption. In detail, 99% of dissolved Tl, 88% of U, 66% of Mo, and 44% of V were removed to the solid phase in comparison to values from less reducing zones. Large parts of the western freshwater lens on Spiekeroog were anoxic. For this reason, the delivery of aquifer derived metals to the ocean via fresh groundwater discharge appeared to be limited. Higher U, Mo, V, and Tl concentrations were observed in the presently developing young freshwater lens in the east of Spiekeroog Island. This suggests that less reducing groundwater lenses may be a source of these metals to the adjacent beach/coastal seawater. Especially for V, freshwater discharge from sandy coastal aquifers may be important, as groundwater concentrations exceeded seawater concentration under oxic as well as anoxic conditions. Regarding the suitability of the freshwater as drinking water, all measured trace metal concentrations were classified as uncritical.


Maternal mortality related to pulmonary embolism in the United States, 2003-2020.
Pulmonary embolism is a leading cause of maternal morbidity and mortality in Western countries. In the United States, pulmonary embolism-related mortality rates have plateaued in the general population after an initial decrease in the past 20 years. This study aimed to describe the changes in pulmonary embolism-related maternal mortality rates in the United States over the past 2 decades. In this epidemiologic study of public vital registration data (death certificates encompassing underlying and contributing causes of death) from the Centers for Disease Control and Prevention Multiple Cause of Death database (2003-2020), we identified all maternal deaths with a pulmonary embolism code listed in any position of the death certificates. We investigated the changes in annual crude pulmonary embolism-related maternal mortality rates for the years 2003 to 2020, considering the effect of the introduction of the pregnancy checkbox in death certificates on the pulmonary embolism-related maternal mortality rates. Overall, 735 pulmonary embolism-related maternal deaths out of 12,871 total maternal deaths (5.7%) were recorded between 2003 and 2020; the overall pulmonary embolism-related maternal mortality rate was 1.02 (95% confidence interval, 0.95-1.10) per 100,000 live births. The pulmonary embolism-related maternal mortality rate increased from 0.93 in 2003 to 1.96 in 2020; however, when accounting for the implementation of the pregnancy checkbox in the death certificates, the trends in pulmonary embolism-related maternal mortality were largely unchanged from 2003 to 2020. The crude pulmonary embolism-related maternal mortality rates differed across maternal age groups (overall 0.61, 1.09, and 3.83 maternal deaths per 100,000 live births for those aged ≤24, 25-39, and ≥40 years, respectively) and racial/ethnicity groups (2.89, 0.47, 0.77, and 0.63 maternal deaths per 100,000 live births for Black non-Hispanics, other non-Hispanics, White non-Hispanics, and Hispanics, respectively). Maternal mortality rates related to pulmonary embolism did not decrease during the period from 2003 to 2020, as opposed to mortality rates related to pulmonary embolism in the general population. More research is required to assess whether improvement in venous thromboembolism prevention and pulmonary embolism diagnosis and management strategies might reduce death owing to pulmonary embolism in this vulnerable population.


Deposition of dibasic esters in the upper respiratory tract of the male and female Sprague-Dawley rat.
Inhalation exposure of the male and female rat to high concentrations of a mixture of the dibasic esters dimethyl succinate (DMS), dimethyl glutarate (DMG), and dimethyl adipate (DMA) results in mild olfactory toxicity. This response is thought to be due to the in situ formation of acidic metabolites via nasal carboxylesterases. The current study was designed to provide inhalation dosimetric information for these vapors. Deposition of DMS, DMG, and DMA was measured in the surgically isolated upper respiratory tracts (URT) of ketamine-xylazine-anesthetized male and female rats under constant velocity flow conditions at a flow rate of 100 ml/min. Deposition of acetone was measured in both genders for comparative purposes. URT deposition efficiencies in excess of 98.3% were observed for DMS, DMG, and DMA in animals exposed to each vapor individually. No gender differences in deposition efficiency were observed for these vapors or for acetone. Deposition of DMS, DMG, and DMA was also measured in animals exposed to all three vapors simultaneously. Deposition efficiency under simultaneous exposure conditions ranged between 97.3 and 98.5%. These values were slightly lower (about 1%) than those obtained under individual exposure conditions (p less than 0.0001). The reduced deposition efficiency may have resulted from competitive inhibition of nasal metabolism due to the simultaneous presence of all three carboxylesterase substrate vapors in nasal tissues. If so, inhalation of dibasic ester vapors would be expected to inhibit the uptake of other carboxylesterase substrate vapors without influencing uptake of vapors which are not substrates for this enzyme. Such was observed in studies using DMS, ethyl acetate (the substrate vapor), and isoamyl alcohol (the nonsubstrate vapor). Specifically, simultaneous exposure to DMS markedly inhibited uptake of ethyl acetate without altering uptake of isoamyl alcohol. Gender differences were not observed in URT deposition of any of the six vapors used in the current study, DMS, DMG, DMA, ethyl acetate, isoamyl alcohol, or acetone, suggesting that gender differences in URT deposition may not be widespread among vapors. The high URT deposition efficiencies of the dibasic esters are consistent with the olfactory toxicity resulting from inhalation exposure to these vapors.


Tuberculosis control in a border state. Treatment of the foreign-born.
As the epidemiology of TB in the United States changes, with more foreign-born and fewer native-born residents developing the disease, treatment can be expected to become more complicated and expensive.