Angiotensin-dependent autonomic dysregulation precedes dilated cardiomyopathy in a mouse model of muscular dystrophy.
What is the central question of this study? Is autonomic dysregulation in a mouse model of muscular dystrophy dependent on left ventricular systolic dysfunction and/or activation of the renin-angiotensin system (RAS) and does it predict development of dilated cardiomyopathy (DCM)? What is the main finding and its importance? The results demonstrate that autonomic dysregulation precedes and predicts left ventricular dysfunction and DCM in sarcoglycan-δ-deficient (Sgcd-/-) mice. The autonomic dysregulation is prevented by treatment of young Sgcd-/- mice with the angiotensin II type 1 receptor blocker losartan. Measurements of RAS activation and autonomic dysregulation may predict risk of DCM, and therapies targeting the RAS and autonomic dysregulation at a young age may slow disease progression in patients. Sarcoglycan mutations cause muscular dystrophy. Patients with muscular dystrophy develop autonomic dysregulation and dilated cardiomyopathy (DCM), but the temporal relationship and mechanism of autonomic dysregulation are not well understood. We hypothesized that activation of the renin-angiotensin system (RAS) causes autonomic dysregulation prior to development of DCM in sarcoglycan-δ-deficient (Sgcd-/-) mice and that the severity of autonomic dysfunction at a young age predicts the severity of DCM at older ages. At 10-12 weeks of age, when left ventricular function assessed by echocardiography remained normal, Sgcd-/- mice exhibited decreases in arterial pressure, locomotor activity, baroreflex sensitivity and cardiovagal tone and increased sympathetic tone compared with age-matched C57BL/6 control mice (P < 0.05). Systemic and skeletal muscle RAS were activated, and angiotensin II type 1 receptor (AT1 R) expression, superoxide and fibrosis were increased in dystrophic skeletal muscle (P < 0.05). Treatment with the AT1 R blocker losartan for 7-9 weeks beginning at 3 weeks of age prevented or strongly attenuated the abnormalities in Sgcd-/- mice (P < 0.05). Repeated assessment of phenotypes between 10 and 75 weeks of age demonstrated worsening of autonomic function, progressive cardiac dysfunction and DCM and increased mortality in Sgcd-/- mice. High sympathetic tone predicted subsequent left ventricular dysfunction. We conclude that activation of the RAS causes severe autonomic dysregulation in young Sgcd-/- mice, which portends a worse long-term prognosis. Therapeutic targeting of the RAS at a young age may improve autonomic function and slow disease progression in muscular dystrophy.


Clinical practice advice on lifestyle modification in the management of nonalcoholic fatty liver disease in Japan: an expert review.
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases worldwide, including in Japan. The Japanese Society of Gastroenterology (JSGE) and the Japanese Society of Hepatology (JSH) have established the Japanese NAFLD/NASH guidelines in 2014 and revised these guidelines in 2020. As described in these guidelines, weight reduction by diet and/or exercise therapy is important for the treatment of NAFLD patients. The I148M single nucleotide polymorphism (rs738409 C > G) of PNPLA3 (patatin-like phospholipase domain-containing 3 protein) is widely known to be associated with the occurrence and progression of NAFLD. In the Japanese, the ratio of PNPLA3 gene polymorphisms found is approximately 20%, which is higher than that found in Westerners. In addition, the ratio of lean NAFLD patients is also higher in Japan than in Western countries. Therefore, the method for lifestyle guidance for the NAFLD patients in Japan would be different from that for the people in Western countries. The problems in the treatment of NAFLD patients include alcohol consumption and sarcopenia. Therefore, guidelines that can help clinicians treat Japanese patients with NAFLD are needed. In this expert review, we summarize evidence-based interventions for lifestyle modification (diet, exercise, alcohol, and sarcopenia) for the treatment of patients with NAFLD, especially from Japan and Asian countries.


Simultaneous determination of three diarylheptanoids and an alpha-tetralone derivative in the green walnut husks (Juglans regia L.) by high-performance liquid chromatography with photodiode array detector.
By optimizing extraction, separation and analytical conditions, a reliable and accurate high-performance liquid chromatographic (HPLC) method coupled with photodiode array detector (DAD) at room temperature is developed for simultaneous determination of three diarylheptanoids (juglanin A, juglanin B, rhoiptelol) and an alpha-tetralone derivative (regiolone) in methanol extracts from the green walnut husks (Juglans regia L.) The sample pretreatment process involved the reflux extraction using methanol as the extract with a ratio of liquor to sample of 15 mL/g. The separation was achieved on a SinoChrom ODS-AP C(18) column with gradient elution using acetonitrile and 2% (v/v) acetic acid in water. The intra-day and inter-day precision (RSD%) for the analytes ranged from 1.08 to 1.51 and 0.60 to 1.13, respectively. The average recoveries obtained were from 88.4% to 96.2% for the analytes with RSDs below 3.13%. The correlation coefficients of the calibration curve exceeded 0.999. The detection limits were 0.51, 0.25, 0.32 and 0.35 ng at a signal-to-noise ratio of 3, respectively. Quantitative analyses of the samples from different grown sites and in obtained different months showed that the contents of the analytes varied significantly. The method was then successfully applied for the detection and isolation of a new diarylheptanoid derivative in the green walnut husks (J. regia L.). The structure of the new compound was elucidated by various spectroscopic methods including 2D NMR techniques (COSY, HMQC, HMBC), HR-ESI-MS and X-ray single-crystal diffraction analysis.


A Multi-Institutional Experience of Proton Beam Therapy for Sinonasal Tumors.
To report the outcomes of sinonasal tumors treated with proton beam therapy (PBT) on the Proton Collaborative Group registry study. Sixty-nine patients with sinonasal tumors underwent curative intent PBT between 2010 and 2016. Patients who received de novo irradiation (42 patients) were analyzed separately from those who received reirradiation (27 patients) (re-RT). Median age was 53.1 years (range, 15.7-82.1; de novo) and 57.4 years (range, 31.3-88.0; re-RT). The most common histology was squamous cell carcinoma in both groups. Median PBT dose was 58.5 Gy (RBE) (range, 12-78.3; de novo) and 60.0 Gy (RBE) (range 18.2-72.3; re-RT), and median dose per fraction was 2.0 Gy (RBE) for both cohorts. Survival estimates for patients who received de novo irradiation and those who received re-RT were calculated using the Kaplan-Meier method. Median follow-up for surviving patients was 26.4 months (range, 3.5-220.5). The 3-year overall survival (OS), freedom from distant metastasis, freedom from disease progression, and freedom from locoregional recurrence (FFLR) for de novo irradiation were 100%, 84.0%, 77.3%, and 92.9%, respectively. With re-RT, the 3-year OS, freedom from distant metastasis, FFDP, and FFLR were 76.2%, 47.4%, 32.1%, and 33.8%, respectively. In addition, 12 patients (17.4%) experienced recurrent disease. Re-RT was associated with inferior FFLR (P = .04). On univariate analysis, squamous cell carcinoma was associated with inferior OS (P < .01) for patients receiving re-RT. There were 11 patients with acute grade 3 toxicities. Late toxicities occurred in 15% of patients, with no grade ≥3 toxicities. No patients developed vision loss or symptomatic brain necrosis. As one of the largest studies of sinonasal tumors treated with PBT, our findings suggest that PBT may be a safe and efficacious treatment option for patients with sinonasal tumors.


Problems in blood alcohol testing of severely injured drivers brought to emergency departments in Japan.
Breath alcohol tests are widely used to control DUI (driving under the influence) in Japan. However, this test is not applied to injured drivers transported to emergency hospitals. In such cases, BAC (blood alcohol concentration) testing should be done to prove DUI. In this paper, we tried to clarify two important issues on the BAC testing in Japan using a questionnaire survey and experiments about contamination of antiseptic ethanol. First, we have described the doctor's dilemma with DUI cases; our present questionnaire survey showed that the police often request the doctor to volunteer blood samples of the suspected drunk drivers brought to emergency hospitals since they have not been granted the right to order blood sampling in Japan. Then, doctors face a serious dilemma whether comply with the police request or not, resulting in widely different responses. Secondly, we have estimated the effects of antiseptic ethanol routinely used as a dermal antiseptic on the BAC tests. Our present experiments showed that uptake of ethanol can occur under certain conditions. Given the actual conditions outlined in the questionnaire, there seem to be a definite risk of ethanol contamination in BAC testing. Obviously, the time has come to discuss problems in BAC testing of injured drivers brought to emergency hospitals in Japan.


Treatment of solar lentigines using a combination of picosecond laser and biophotonic treatment.
Treating solar lentigines using picosecond-switched lasers that selectively remove the excess pigment was combined with Kleresca® biophotonic treatment. This therapy uses fluorescent light energy to stimulate healing by increasing collagen production and reducing inflammation. Combining these therapies successfully removed solar lentigines and achieved normalized and rejuvenated treated skin.


Epidemiology of non-submersion injuries in aquatic sporting and recreational activities.
Although the issues of drowning and near-drowning in aquatic sporting and recreational activities receive considerable attention in the epidemiological literature, there is not a recognised literature on non-submersion injuries occurring in these activities. This review draws together the epidemiological literature on non-submersion injuries and describes the incidence, nature and causes of these injuries, common risk factors, and strategies for prevention. Activities covered by the review include swimming, diving, boating, surf sports, fishing, water polo and water sliding. For most activities there is a dearth of good quality descriptive studies, with most involving cases-series designs and few providing estimates of incidence. Inconsistencies in inclusion criteria and the reporting of incidence rates makes comparisons within and between activities difficult. Incidence rates were identified for most activities and in general the incidence of injury was low, especially for more serious injury. However, some activities were associated with severely disabling injury, such as spinal cord injury (diving) and amputation (from propeller strikes in water skiing and swimming). Only three studies reporting the significance of postulated risk factors were identified. Lack of knowledge about the water being entered and alcohol consumption are significant risk factors in recreational diving; increased blood alcohol concentrations were reported to increase the risk of death in boating; and obesity and tandem riding were reported to increase the risk of injury on public water slides. Few evaluations of preventive measures were identified. Two studies reported reductions in the incidence of water slide injuries following the introduction of design changes and supervision, but neither had a non-intervention comparison group. Improvements in swimming and diving skills were reported in three studies, but these were not designed to measure changes in the risk of injury.This review demonstrates that there is a need for well-designed epidemiological research on non-submersion injury in aquatic sporting and recreational activities. The first priority should be for studies designed to describe accurately the incidence, nature, severity and circumstances of these injuries, followed by research on the significance of postulated risk factors. Once this research has been undertaken, interventions targeted at reducing the incidence of injury in aquatic sporting and recreational activities can be designed and evaluated.


The association between diabetes status, HbA1c, diabetes duration, microvascular disease, and bone quality of the distal radius and tibia as measured with high-resolution peripheral quantitative computed tomography-The Maastricht Study.
In this small cross-sectional study of predominantly well-treated participants with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was associated with lower cortical density and thickness and higher cortical porosity at the distal radius, lower trabecular thickness at the distal tibia, and higher trabecular number at both sites. To examine the association between diabetes status and volumetric bone mineral density (vBMD), bone microarchitecture and strength of the distal radius and tibia as assessed with HR-pQCT. Additionally-in participants with type 2 diabetes (T2DM), to examine the association between HbA1c, diabetes duration, and microvascular disease (MVD) and bone parameters. Cross-sectional data from 410 (radius) and 198 (tibia) participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral glucose tolerance test and medication history. After full adjustment, prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and strength of the radius and tibia, except for lower trabecular number (Tb.N) of the tibia (- 4%) in prediabetes and smaller cross-sectional area of the tibia (- 7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (- 5%), cortical thickness (- 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (- 13%) of the tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the radius. The presence of MVD was not associated with any bone parameters. In this study with predominantly well-treated T2DM participants with relatively short-term diabetes duration, inadequate blood glucose control was negatively associated with cortical bone measures of the radius. In contrast, trabecular number was increased at both sites. Studies of larger sample size are warranted for more detailed investigations of bone density and bone quality in patients with T2DM.


Two peculiar types of enchondromatosis.
On the basis of 3 personal observations and of 6 cases from the literature, two peculiar types of enchondromatosis are delineated: 1. Enchondromatosis with generalized, irregular vertebral lesions, and 2. Generalized enchondromatosis with mild platyspondyly.


Investigating the role of BN-domains of FlhF involved in flagellar synthesis in Campylobacter jejuni.
FlhF protein is critical for intact flagellar assembly in Campylobacter jejuni. It is a putative GTPase with B-, N- and G-domains. However, the role of the B- and N-domains in flagella biosynthesis remains unclear in C. jejuni. This study demonstrated that both the B- and N-domains are essential for flagellar synthesis, with the absence of B- and/or N-domains showing truncated variants of FlhF by TEM. Point mutations in the B- and N-domains (T13A, K159A, G231A) also induced flagella abnormalities. Furthermore, significant defects in GTPase activity and polar targeting of FlhF were triggered by point mutations of B- and N-domains. Flagella gene expression and transcription were also significantly disrupted in flhF(T13A), flhF(K159A) and flhF(G231A) strains. This study initially explored the effects of B- and N-domains on flagella synthesis. We speculated that B- and N-domains may directly or indirectly cause flagella abnormalities by affecting flagellar gene expression or GTPase activity, which helps us better understand the function of FlhF in flagella synthesis.


On the potential role of cyclosporin in the treatment of lymphoproliferative diseases.
Lymphomas and leukemias, as cancers of the immune system, may still retain some susceptibility to regulatory mechanisms which govern the proliferation of their cells of origin. According to this concept, an enhanced immune suppression as induced by irradiation and chemotherapy may contribute to their cytotoxic effect in inducing and maintaining a remission of the disease. Cyclosporin selectively and reversibly inhibits activation and proliferation of both normal and neoplastic T lymphocytes. In-vitro experiments and preliminary clinical data from small uncontrolled studies indicate that cyclosporin might be a promising agent in the treatment of mycosis fungoides, Hodgkin's disease, acute leukemia, and possibly other lymphoproliferative disorders, but the experience is still limited and no definitive conclusions may be made. In addition to its direct effect on lymphocytes, cyclosporin reverses the resistance of cancer cells to several antineoplastic agents and may thus find its place in combination with chemotherapy. It is hoped that a more systematic basic and clinical research will help define the role of this new therapeutic approach.


An unusual suppression of immune response: pretreatment with Poly(Glu60,Phe40) suppresses response to poly(Glu60,Phe40).
The synthetic random copolymer poly( Glu60 , Phe40 ) ( GPhe ) is an excellent immunogen in SWR/J (H-2q) mice. The intravenous injection of soluble GPhe by itself led to antibody production and GPhe -specific T-lymphocyte proliferation. The proliferating lymphocyte was sensitive to anti-Thy 1.2 and anti-Ly 1 antisera. A subsequent immunization with GPhe should therefore lead to an enhanced response. Yet, a single intravenous injection of an aqueous solution of GPhe suppressed the immune response to a subsequent immunization with GPhe in CFA as measured by GPhe -specific plaque-forming colonies, ELISA, T-cell proliferation, and delayed-type hyper-sensitivity. The suppression was not transferable from pretreated mice into normal or irradiated syngeneic recipients with either sera or lymphoid cells. The antibody generated from the pretreatment could not be responsible for the suppression as injection of SWR anti- GPhe antibody into SWR/J mice enhanced, rather than suppressed, the response to the subsequent immunization with GPhe . Pretreatment of mice with a rabbit anti-idiotypic antiserum produced against (SWR anti- GPhe antisera) had no effect on the immune response to GPhe . Thus, the suppression cannot be explained by a simple B-cell tolerance mechanism. This type of unusual suppression was observed only with mice of H-2q haplotype and not with mice of H-2 haplotypes a and k which are also responders to GPhe .


Tuberculin response of Sri Lankan children after BCG vaccination at birth.
A total of 740 healthy children aged between 3 months and 11 years who had received BCG vaccination in the first month of life were Mantoux tested in Sri Lanka. Despite 97% having a visible scar following vaccination, 80% showed Tuberculin anergy (0-1 mm). Those without a scar showed no response. There was no correlation between scar size and the Mantoux response. A low mean Mantoux reaction was seen at all ages: 3.5 mm at 3 months, 3.2 mm at 18 months, 1.8 mm at 5-7 years and 1.9 mm at 9-11 years. A significant waning of the Mantoux reaction occurred at 5-7 years but there was no significant change at 9-11 years. Children who had received routine revaccination at 10 years, having received the first at birth, had a significantly higher mean Mantoux reaction (9.6 mm) when tested 3 months after revaccination. In 90 bacteriologically proven tuberculous patients, there was a significantly increased Mantoux reaction compared to all other groups. 1 T.U. PPD RT 23 (with tween 80) was used in all instances for Mantoux testing. The present study shows that routine BCG vaccination at birth, using a reduced dose of 0.05 ml, is unlikely to interfere subsequently with the diagnostic value of the Mantoux test. However, revaccination at 10 years may do so.


Comparison of two approaches in microsurgical varicocelectomy in Chinese infertile males.
To compare the outcomes of two approaches (inguinal and subinguinal) of microsurgical varicocelectomy (MV) in Chinese infertile men. 120 infertile men who met the inclusion criteria were randomly assigned to two groups and operated with MV using different approaches. The outcomes and complications were then compared. The two groups were similar in all aspects except the percentage of patients using analgesic at 27 h postoperatively (57.6% in the inguinal group, 37.5% in the subinguinal group; p < 0.05). Spontaneous pregnancy was achieved at a ratio of 33.9% in the inguinal group and 30.4% in subinguinal group. The median values of semen parameters were significantly improved postoperatively in both groups. Both approaches are effective methods in the repair of varicocele in infertile men, but more analgesic medication at the first day after operation may be required in inguinal group.


Comprehensive overview of autoantibody isotype and subclass distribution.
The presence of autoreactive antibodies is a hallmark of many autoimmune diseases. The effector functions of (auto)antibodies are determined by their constant domain, which defines the antibody isotype and subclass. The most prevalent isotype in serum is IgG, which is often the only isotype used in diagnostic testing. Nevertheless, autoantibody responses can have their own unique isotype/subclass profile. Because comparing autoantibody isotype profiles may yield new insights into disease pathophysiology, here we summarize the isotype/subclass profiles of the most prominent autoantibodies. Despite substantial variation between (and within) autoantibody responses, this unprecedented comparison shows that autoantibodies share distinctive isotype patterns across different diseases. Although most autoantibody responses are dominated by IgG (and mainly IgG1), several specific diseases are characterized by a predominance of IgG4. In other diseases, IgE plays a key role. Importantly, shared features of autoantibody isotype/subclass profiles are seen in clinically unrelated diseases, suggesting potentially common trajectories in response evolution, disease pathogenesis, and treatment response. Isotypes beyond IgG are scarcely investigated in many autoantibody responses, leaving substantial gaps in our understanding of the pathophysiology of autoimmune diseases. Future research should address isotype/subclass profiling in more detail and incorporate autoantibody measurements beyond total IgG in disease models and clinical studies.


The effects of acupressure on postoperative nausea and vomiting among patients undergoing laparoscopic surgery: A meta-analysis of randomized controlled trials.
Laparoscopic surgery is one of the most commonly performed surgeries in general surgery, with fewer side effects and rapid recovery. Postoperative nausea and vomiting (PONV) remains the main challenge that confronts the prognosis of this minimally invasive surgery. We aimed to evaluate the effect of acupressure, a nonpharmacological non-invasive method, on the incidence of nausea and vomiting following laparoscopic surgery within the early phase (first six hours postoperatively) and the extended phase (for at least 24 h postoperatively). We searched PubMed, Cochran, Scopus, Web of Science, Google scholar, and Wiley for randomized controlled trials that evaluated the effect of acupressure on PONV in patients undergoing laparoscopy. Data were extracted and analyzed in a random model, and pooled risk ratios (RRs) with their respective 95% confidence intervals (CIs) were calculated. Eleven trials were included in the meta-analysis, comprising 941 patients. Most of the included patients were females undergoing gynecological laparoscopy or laparoscopic cholecystectomy. Acupressure significantly lowered the incidence of nausea and vomiting, within the early phase (RR = 0.62, 95% CI [0.44 to 0.88]; p = 0.008), (RR = 0.5, 95% CI [0.30 to 0.84]; p = 0.008), and the extended phase (RR = 0.65, 95% CI [0.52 to 0.83]; p = 0.0003), (RR = 0.44, 95% CI [0.32 to 0.61]; p < 0.00001), respectively. Moreover, acupressure significantly reduced the need for rescue antiemetic drugs in both phases (p < 0.05). Acupressure is an effective procedure for reducing nausea, vomiting, and the need for antiemetic drugs after laparoscopic surgery.


Survivorship of highly constrained prostheses in primary and revision total knee arthroplasty: analysis of 6070 cases.
Concerns exist about the survival and complication rates of highly constrained total knee arthroplasty (TKA) prostheses. The aims of this study were to determine if there were differences between the revision and complication rates of fully stabilized (FSTKA) and hinged (HTKA) TKA, when used in both primary and revision procedures. Survivorship of all highly constrained TKA prostheses implanted over a 17 year period were analysed by the Australian Orthopaedic Association National Joint Replacement Registry. The primary outcome measure was time to first revision using Kaplan Meier estimates of survivorship. In the primary setting, the cumulative percent revision at 11 years was higher for HTKA than for FSTKA prostheses (P = 0.014). However, this finding was only significant for patient >75 years. In the revision setting, there were no differences in the revision rates for either category of prosthesis for any age group. For the indication of periarticular/periprosthetic fracture, HTKA resulted in a lower revision rate than FSTKA in both primary and revision cohorts. There were no differences in the rates of revision for infection and aseptic loosening for either prosthesis type in primary or revision settings. The revision risk for periprosthetic fracture was higher after HTKA prostheses. Both FSTKA and HTKA prostheses provide similar outcomes in primary and revision procedures except for the setting of periarticular/periprosthetic fracture, where a HTKA should be used. In elderly patients, a FSTKA prosthesis is recommended as the risk of periprosthetic fracture is higher with a HTKA.


Top-down controls on nutrient cycling and population dynamics in a model estuarine photoautotroph-heterotroph co-culture system.
Viral lysis and protistan grazing are thought to be the major processes leading to microbial mortality in aquatic environments and thus regulate community diversity and biogeochemical cycling characteristics. Here, we studied nutrient cycling and bacterial responses to cyanophage-mediated photoautotroph lysis and ciliate predation in a model Synechococcus-heterotroph co-culture system. Both viral lysis and Euplotes grazing facilitated the transformation of organic carbon from biomass to dissolved organic matter with convention efficiencies of 20%-26%. The accumulation of ammonium after the addition of phages and ciliates suggested the importance of recycled NH4+ occurred in the interactions between Synechococcus growth and heterotrophic bacterial metabolism of photosynthate. The slower efficiency of P mineralization compared to N (primarily ammonium) indicated that P-containing organic matter was primarily integrated into bacterial biomass rather than being remineralized into inorganic phosphate under C-rich conditions. In the cyanophage addition treatment, both Fluviicola and Alteromonas exhibited rapid positive responses to Synechococcus lysing, while Marivita exhibited an apparent negative response. Further, the addition of Euplotes altered the incubation system from a Synechococcus-driven phycosphere to a ciliate-remodelled zoosphere that primarily constituted grazing-resistant bacteria and Euplotes symbionts. Top-down controls increased co-culture system diversity and resulted in a preference for free-living lifestyles of dominant populations, which was accompanied by the transfer of matter and energy. Our results indicate top-down control was particularly important for organic matter redistribution and inorganic nutrient regeneration between photoautotrophs and heterotrophs, and altered bacterial lifestyles. This study consequently sheds light on marine biogeochemical cycling and the interaction networks within these dynamic ecosystems.


Perceived compassionate care and associated factors among patients with mental illness at Tibebe Ghion specialized and Felege Hiwot comprehensive specialized hospital, Northwest Ethiopia.
Compassion is the first ethical principle of health care to provide high- quality care that influences patient satisfaction and treatment outcome. However, there is limited data on the level of compassionate mental health care practice in low-resource countries like Ethiopia. This study aimed to assess the level of perceived compassionate care and associated factors among patients with mental illness at Tibebe Ghion specialized and Felege Hiwot comprehensive specialized hospital, North West, Ethiopia, 2022. An institutional-based cross-sectional study design was conducted from June 18 to July 16, 2022, at Tibebe Ghion Specialized and Felege Hiwot Comprehensive Specialized Hospital. A systematic random sampling technique was used. The level of perceived compassionate care was assessed by the validated 12-item Schwartz Center Compassionate Care Scale among 423 patients with mental illness. Epicollect-5 was used to collect data, which was then exported to the Statistical Product and Service solution version 25 for analysis. Variables with a P-value < 0.05, and 95% confidence interval (CI) were used to declare significant variables at the multivariate logistic regression analysis. The level of perceived good compassionate care was 47.5% (95% CI 42.6%-52.4%). Factors including urban residence (AOR = 1.90; 95%CI 1.08-3.36), duration of illness < 24 months (AOR = 2.68; 95% CI 1.27-5.65), strong social support (AOR = 4.43; 95%CI 2.16-9.10), shared decision making (AOR = 3.93; 95% CI 2.27-6.81), low perceived stigma(AOR = 2.97; 95% CI 1.54-5.72) and low patient anticipated stigma (AOR = 2.92; 95% CI 1.56-5.48) were positively associated with good compassionate care. Less than half of the patients had received good compassionate care. Compassionate mental health care needs public health attention. Policymakers should emphasize on compassionate care continuity by including it in the health care curriculum and design appropriate policies to strengthen compassionate care.


[Effectiveness of initial antibiotic therapy for treatment of contact lens-related bacterial keratitis].
Contact lens-related microbial keratitis is a cause of potentially sight-threatening corneal opacification. Effective initial antimicrobial therapy is crucial to prevent long-term complications. This investigation was undertaken to test the effectiveness of current routine empirical antibiotic treatment regimens. All consecutive cases of contact lens-related keratitis presenting in the outpatient clinic of the Department of Ophthalmology at the Medical University of Innsbruck between January 2010 and April 2012 were retrospectively analyzed. Cultures were positive in 69 out of the 123 cases included in the study. Culture results identified 59.4 % Gram positive strains, 50.7 % Gram negative strains and 7.2 % fungal strains. Mixed infections accounted for 29 % of cases. The combination of an aminoglycoside and a second generation quinolone antibiotic was the most common initial treatment regimen (87.8 %). In vitro this regimen was less effective compared to combinations of moxifloxacin and ciprofloxacin or moxifloxacin and gentamicin. Empirical combined regimens remain an effective treatment of contact lens-related keratitis. Fluoroquinolones proved to be inadequate for monotherapy.


A review of the efficacy of rosuvastatin in patients with type 2 diabetes.
It has been estimated that 92% of individuals with type 2 diabetes, without cardiovascular disease (CVD), have a dyslipidaemic profile. Several guidelines on cardiovascular risk now recommend that patients with diabetes should be considered at high risk of CVD and should thus receive lipid-lowering therapy to reduce low-density lipoprotein cholesterol (LDL-C) to below 2.5 mmol/L. Since their introduction in 1987, statins have revolutionized the management of CVD. The most recent statin to be introduced, rosuvastatin, has been shown to be the most effective at lowering LDL-C, as well as consistently raising HDL-C across the 10-40 mg dose range. This has been confirmed by many studies, including the Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study in which rosuvastatin 10 mg was shown to be more effective than commonly used doses of other statins, both for LDL-C reduction and achieving treatment target goals. The effectiveness of rosuvastatin has also been studied in type 2 diabetes patients in three studies: the URANUS (Use of Rosuvastatin vs. Atorvastatin iN type 2 diabetes mellitUS), ANDROMEDA (A raNdomized, Double-blind study to compare Rosuvastatin [10 & 20 mg] and atOrvastatin [10 & 20 Mg] in patiEnts with type II DiAbetes) and CORALL (COmpare Rosuvastatin [10-40 mg] with Atorvastatin [20-80 mg] on apo B/apo A-1 ratio in patients with type 2 diabetes meLLitus and dyslipidaemia) studies. URANUS and ANDROMEDA showed rosuvastatin to be more effective than atorvastatin at reducing LDL-C and achieving treatment target goals. CORALL demonstrated rosuvastatin 10, 20 and 40 mg to be more effective at lowering LDL-C than 20, 40 and 80 mg of atorvastatin, respectively. Ongoing studies will evaluate whether these properties of rosuvastatin translate into beneficial effects on atherosclerosis and significant reductions in cardiovascular events.


Immunopotentiating significance of conventionally used plant adaptogens as modulators in biochemical and molecular signalling pathways in cell mediated processes.
Natural products are of great surge in the identification of chemopreventive agents and biologically active molecules for the development of new promising therapeutic agents. These agents influence the cascade of biochemical and molecular signalling pathways involved in numerous physiological and pathological processes. The natural agents combat the dogma associated with the most dreaded, unconquered health concern and a multigenic disease- cancer. A category of plants known as adaptogens maintain perturbed homoeostasis, augment adaptations to noxious stimuli (exposure to cold, heat, pain, general stress, infectious organisms) and offer endurance to attenuate several disorders in human beings. The well known adaptogens and immunomodulators such as Rhodiola rosea, Withania somnifera, Tinospora cordifolia, Bacopa monnieri, Emblica officinalis, Glycyrrhiza glabra, Asparagus racemosus, Ocimum sanctum and Panax notoginseng claimed to have significant antioxidant and anticarcinogenic properties due to the presence of various biologically active chemical compounds. Their immunopotentiating activity is mediated through the modulation of T-cell immunity biochemical factors, transcription factors, some genes and factors associated with tumor development and progression. The combinatory formulation of active immunostimulating constituents from these plants may provide better homeostasis. These immunostimulant factors suggest their potential therapeutic significance in adjuvant or supportive therapy in cancer treatment.


Characterization of the polypeptides synthesized in cells infected with a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture.
The intracellular synthesis of virus-specific polypeptides in cells infected with the wild-type virus of HVJ (HVJ-W) (haemagglutinating virus of Japan--the Sendai strain of parainfluenza 1 virus) and with a temperature-sensitive (ts) mutant (HVJ-pB) derived from an HVJ carrier culture has been analysed by polyacrylamide gel electrophoresis. At the permissive temperature (32 degrees C), all of the known virus structural polypeptides were identified in cells infected with each strain of virus and in addition to the non-structural polypeptides B and C, another polypeptide at the region with a molecular weight of 26,000 to 27,000 (26 to 27K) could be detected in infected cells. At the non-permissive temperature (38 degrees C), the synthesis of the polypeptide M was markedly restrained in cells infected with HVJ-pB, while other major virus polypeptides were present in approximately comparable amounts to cells infected with the wild-type virus. A non-structural polypeptide with a molecular weight of 105K was dominant in ts mutant infected cells at higher temperatures and disappeared after temperature-shift from 38 degrees to 32 degrees C. The production of the non-structural polypeptides B and 27K was also temperature-sensitive. The molecular weights of the polypeptides B, M and 27K in HVJ-pB infected cells were larger than those of the corresponding polypeptides in HVJ-W infected cells. The synthesis of the M protein in HVJ-prinfected cells started just after lowering the incubation temperature and the newly made M protein was successfully incorporated into virus particles.


The impact of the COVID-19 pandemic on paediatric surgical volumes in Africa: A retrospective observational study.
The aim of this study is to investigate the impact that COVID-19 had on the pattern and trend of surgical volumes, urgency and reason for surgery during the first 6 months of the pandemic in sub-Saharan Africa. This retrospective facility-based study involved collection of paediatric operation data from operating theatre records across 5 hospitals from 3 countries: Zimbabwe, Zambia and Nigeria over the first half of 2019 and 2020 for comparison. Data concerning diagnosis, procedure, anaesthesia, grade, speciality, NCEPOD classification and indication was collected. The respective dates of enactment of cancellation policies in each country were used to compare changes in weekly median surgical case volume before cancellation using the Wilcoxon Sign-Rank Test. A total of 1821 procedures were recorded over the study period. Surgical volumes experienced a precipitous drop overall from a median of 100 cases/week to 50 cases/week coinciding with cancellation of surgical electives. Median accumulated weekly procedures before COVID-related cancellation were significantly different from those after cancellation (p = 0.027). Emergency surgery fell by 23.3% while electives fell by 78,9% (P = 0.042). The most common primary indication for surgery was injury which experienced a 30.5% drop in number of procedures, only exceeded by congenital surgery which dropped 34.7%. The effects of surgical cancellations during the covid-19 pandemic are particularly devastating in African countries where the unmet need and surgical caseload are high. Continued cancellations that have since occurred will cause similar drops in surgical case volume that these health systems may not have the resilience to recover from. Level II.


Targeted Delivery of Epirubicin to Cancer Cells by Polyvalent Aptamer System in vitro and in vivo.
The clinical use of Epirubicin (Epi), as an anthracycline drug, is limited because of its cardiotoxicity. Here, an Epirubicin (Epi)-modified polyvalent aptamer system (MPAS) conjugate was developed for the treatment of both murine colon carcinoma cells (C26) and breast cancer cells (MCF-7). Epi-MPAS conjugate formation was evaluated by fluorometric analysis. Release profiles of Epi from the developed conjugate were analyzed at pHs 5.4 and 7.4. For MTT assay (cytotoxic study) C26 and MCF-7 (target cells) and CHO cells (Chinese hamster ovary cell, nontarget) were treated with Epi, MPAS and Epi-MPAS conjugate. Internalization was assessed by fluorescence imaging and flow cytometry analysis. The designed conjugate was used for prohibition of tumor growth in vivo. Release of Epi from the Epi-MPAS conjugated was pH-dependent (more release at pH 5.5). Flow cytometry analysis and MTT assay showed that Epi-MPAS conjugate could significantly enhance the cellular uptake of Epi and increase its cytotoxicity in target cells as compared with non-targeted cell (CHO). Additionally, this complex could efficiently prohibit the tumor growth in vivo. In conclusion, the developed drug delivery system had the characteristics of efficient Epi loading, pH-dependent drug release and tumor targeting in vitro and in vivo.


Clinical outcomes of endovascular treatment for intracranial pial arteriovenous fistulas.
Pial arteriovenous fistula is a rare disease and surgical treatment for these lesions is difficult. We present our clinical outcomes of endovascular treatment for intracranial pial arteriovenous fistula (AVF). We reviewed the clinical and radiologic data of 16 patients with intracranial pial AVFs who were treated endovascularly at the Beijing Tiantan Hospital between 1998 and 2008. Six patients presented with intracranial hemorrhage, six presented with headaches, two with seizures, one with neurologic deficit, and one with transient ischemic attack. Cerebral angiograms showed that these pial AVFs were supplied by the middle cerebral artery (n = 6), the anterior cerebral artery (n = 4), the posterior cerebral artery (n = 3), the basilar artery (n = 2), and the inferoposterior cerebellar artery (n = 1). All AVFs were associated with large venous varices. One of the lesions had two associated feeding artery aneurysms. The venous drainage was deep in 11 lesions. All AVFs were embolized transarterially through the feeding arteries. Coils was used in 14 patients with a combination of liquid embolic agent (n-butyl cyanoacrylate and Onyx [Micro Therapeutics Inc., Irvine, CA]) in five patients; Onyx was used in three patients. Immediate complete angiographic obliteration was achieved in 13 patients. Three patients incompletely treated with coils showed complete obliteration at follow-up. Twelve patients experienced an angiographic and clinical cure without any complications at 3 months. Three patients (18.75%) experienced hydrocephalus after the procedure caused by venous thrombosis. Glasgow outcome scores were good in 15 patients (93.75%) and poor in 1 patient (6.2%) at follow-up. Transarterial embolization of the arterial feeders using coils and/or liquid embolic agents may be a good treatment for pial AVFs. Hydrocephalus caused by venous thrombosis is the main complication.


Insulators to improve expression of a 3(')IgH LCR-driven reporter gene in transgenic mouse models.
A locus control region (LCR) containing four transcriptional enhancers lies downstream of the IgH chain locus. We studied transgenes carrying a 3(')IgH LCR-driven GFP reporter gene for expression and B cell differentiation stage specificity. We also compared transgenes that were or were not flanked by two copies of the beta-globin HS4 insulator, an element defined by its ability to protect transgenes from the influences of surrounding genes at the insertion site. Results indicate that insulators are instrumental in sustaining GFP expression in GFP-3(')LCR transgenic mice when they were included. Flow cytometry experiments reported a strictly B cell specific GFP expression from pre-B cells in bone marrow to mature B cells in spleen. Despite addition of 5(')HS4 insulators to the GFP-3(')LCR construct, complete transgene silencing occurred in some transgenic lines and was systematically observed in ageing animals from all lines.


Sperm flow cytometric parameters are associated with ICSI outcome.
The association of sperm nuclear chromatin condensation and ploidy with embryo development and outcome after intracytoplasmic sperm injection (ICSI) was explored. The study population consisted of 16 couples referred to Ioannina University Medical School In vitro Fertilization Unit with male factor infertility and serious impairments in sperm nuclear chromatin condensation and ploidy, according to sperm flow cytometry. Additionally, 20 couples with male factor infertility and relatively high sperm flow cytometry parameters participated as controls. The 35 cycles of the study population were characterized by a lower fertilization rate (P<0.001) as well as decreased grade A embryo rate (P=0.004) and increased grade C embryo rate (P=0.028), compared with the 29 cycles of the control group. Additionally, a significantly elevated arrested embryo rate (P<0.001) and a decreased clinical pregnancy rate (P<0.020) were observed in the couples of the study population. Consequently, high levels of sperm nuclear chromatin condensation abnormalities and sperm aneuploidies are probably associated with lower fertilization rates, impaired embryo quality, elevated arrested embryo rates and decreased pregnancy rates. These preliminary results strongly support the use of sperm flow cytometry as a potential prognostic tool of ICSI outcome.


Application of the Oral Minimal Model to Korean Subjects with Normal Glucose Tolerance and Type 2 Diabetes Mellitus.
The oral minimal model is a simple, useful tool for the assessment of β-cell function and insulin sensitivity across the spectrum of glucose tolerance, including normal glucose tolerance (NGT), prediabetes, and type 2 diabetes mellitus (T2DM) in humans. Plasma glucose, insulin, and C-peptide levels were measured during a 180-minute, 75-g oral glucose tolerance test in 24 Korean subjects with NGT (n=10) and T2DM (n=14). The parameters in the computational model were estimated, and the indexes for insulin sensitivity and β-cell function were compared between the NGT and T2DM groups. The insulin sensitivity index was lower in the T2DM group than the NGT group. The basal index of β-cell responsivity, basal hepatic insulin extraction ratio, and post-glucose challenge hepatic insulin extraction ratio were not different between the NGT and T2DM groups. The dynamic, static, and total β-cell responsivity indexes were significantly lower in the T2DM group than the NGT group. The dynamic, static, and total disposition indexes were also significantly lower in the T2DM group than the NGT group. The oral minimal model can be reproducibly applied to evaluate β-cell function and insulin sensitivity in Koreans.


Investigation of antibiotics in mollusks from coastal waters in the Bohai Sea of China.
This study focused on the presence and distribution of 22 antibiotics, including eight quinolones, nine sulfonamides and five macrolides in mollusks from the Bohai Sea of China. 190 samples of eleven species were collected in 2006, 2007 and 2009. Laboratory analyses revealed that antibiotics were widely distributed in the mollusks with quinolones as the major compounds with concentrations of 0.71~1575.10 μg/kg, which were up to two orders of magnitude higher than those of sulfonamides (0~76.75 μg/kg) and macrolides (0~36.21 μg/kg). The contents of quinolones and macrolides did not show significant changes from 2006, 2007 to 2009, while sulfonamides decreased significantly from 2006 to 2009. Compared with other sites, the city of Dalian was more polluted with quinolones, while Beidaihe was more contaminated with erythromycin and sulfapyridine. In addition, Mactra veneriformis and Meretrix merehjgntrix Linnaeus contained higher concentrations of quinolones and sulfamonomethoxine, while Mytilus edulis had higher levels of erythromycin and sulfapyridine.


Lymphatic network of kidney. II. Effect of diuretics on intrarenal renin release.
The individual effects of chlorothiazide, furosemide, and mannitol on renin activity in renal lymph have been studied in dogs. Elevation of renin activity in lymph is noted following infusion with either chlorothiazide or furosemide, while a reduction of renin activity in renal lymph is noted after mannitol infusion. The importance of elevated sodium levels in the proximal end of the distal tubule and its effects on renin release in kidney interstitium is stressed. More work is advocated to elucidate fully the role of renin when released intrarenally.


Finding sexual health aids after cancer: are cancer centers supporting survivors' needs?
Sexual dysfunction is one of the most prevalent and distressing treatment-related side effects for both male and female cancer survivors. Survivorship care guidelines recommend therapeutic sexual aids to help improve sexual problems. However, little is known about the availability of sexual aids and resources at cancer centers. Twenty-five comprehensive cancer centers affiliated with both the National Cancer Institute and the National Comprehensive Care Network were surveyed using the "mystery shopper" method to determine whether various types of sexual aids were available at the centers. Staffs from cancer center staff retail stores and patient boutiques were queried in separate telephone calls regarding the availability of these aids for and women. Of the 25 centers contacted, 23 (92%) responded about aids for men, and 22 (88%) responded about aids for women. Eighty-seven percent of the centers reported having no sexual aids available for men, and 72% of centers reported having no aids available for women. The most common advice given to mystery shoppers was a suggestion to use the internet. Only one center had numerous aids/resources for both men and women. The large majority of cancer centers reported having no sexual aids or other sexual health resources available for men or women. Results underscore the widespread lack of resources to promote sexual health rehabilitation at major cancer centers, both for male and female survivors.


Was Feyerabend a Popperian? Methodological issues in the History of the Philosophy of Science.
For more than three decades, there has been significant debate about the relation between Feyerabend and Popper. The discussion has been nurtured and complicated by the rift that opened up between the two and by the later Feyerabend's controversial portrayal of his earlier self. The first part of the paper provides an overview of the accounts of the relation that have been proposed over the years, disentangles the problems they deal with, and analyses the evidence supporting their conclusions as well as the methodological approaches used to process that evidence. Rather than advancing a further speculative account of the relation based on Feyerabend's philosophical work or autobiographical recollections, the second part of the paper strives to clarify the problems at issue by making use of a wider range of evidence. It outlines a historical reconstruction of the social context within which Feyerabend's intellectual trajectory developed, putting a special emphasis on the interplay between the perceived intellectual identity of Feyerabend, Feyerabend's own intellectual self-concept, and the peculiar features of the evolving Popperian research group.


Ostomy closure for recurrent stomal hemorrhage: an indication for prophylactic sclerotherapy in biliary atresia.
Two patients with failed drainage procedures for biliary atresia are presented in whom major hemorrhage from esophageal varices followed shortly after ostomy closure for recurrent stomal bleeding. Before ostomy closure is contemplated in these patients, evaluation for esophageal varices and their prophylactic obliteration with sclerotherapy is recommended.


[Pseudomonas-like bacteria (group Ve biotype 1) isolated from a subdiaphragmatic abscess (author's transl)].
Pseudomonas like bacteria group Ve biotype I was isolated three times from the specimens taken by thorocenthessis from a patient with subdiaphragmatic abscess who was admitted to the Thoracic Diseases Clinic in the University of Ankara School of Medicine.


Risk factors for poor work functioning of persons with schizophrenia in rural China.
The long-term work performance of persons with schizophrenia in the community is unclear. This study examined the status of long-term work functioning and the predictors of poor work status among patients with schizophrenia in a Chinese rural area. A 10-year follow-up investigation (1994-2004) of a cohort (n = 510) of persons with schizophrenia was conducted in Xinjin County, Chengdu, China. Compared with baseline data, work functioning of patients with schizophrenia deteriorated after 10 years. The rates of not working increased significantly from 12.0% in 1994 to 23.0% in 2004. Bivariate analyses showed that the poor work functioning in 2004 was significantly associated with male gender, older age, older age of first onset, higher level of education, longer duration of illness, lower family economic status, lack of caregivers, poor work status in 1994, living in shabby or unstable house, marked symptoms, and higher score on the Social Disability Screening Schedule (SDSS). In multiple logistic regression analyses, higher score of SDSS and poor work status in 1994 were identified as unique predictors of poor work status in 2004. The status of work functioning of persons with schizophrenia decreased over the course of the illness. The risk factors for poor work functioning and specific socio-cultural environment should be considered in planning community mental health services and rehabilitation for these patients.


Local diversity of heathland Cercozoa explored by in-depth sequencing.
Cercozoa are abundant free-living soil protozoa and quantitatively important in soil food webs; yet, targeted high-throughput sequencing (HTS) has not yet been applied to this group. Here we describe the development of a targeted assay to explore Cercozoa using HTS, and we apply this assay to measure Cercozoan community response to drought in a Danish climate manipulation experiment (two sites exposed to artificial drought, two unexposed). Based on a comparison of the hypervariable regions of the 18S ribosomal DNA of 193 named Cercozoa, we concluded that the V4 region is the most suitable for group-specific diversity analysis. We then designed a set of highly specific primers (encompassing ~270 bp) for 454 sequencing. The primers captured all major cercozoan groups; and >95% of the obtained sequences were from Cercozoa. From 443 350 high-quality short reads (>300 bp), we recovered 1585 operational taxonomic units defined by >95% V4 sequence similarity. Taxonomic annotation by phylogeny enabled us to assign >95% of our reads to order level and ~85% to genus level despite the presence of a large, hitherto unknown diversity. Over 40% of the annotated sequences were assigned to Glissomonad genera, whereas the most common individually named genus was the euglyphid Trinema. Cercozoan diversity was largely resilient to drought, although we observed a community composition shift towards fewer testate amoebae.


New insights into the role of the glutamic acid of the E-box motif in group B Streptococcus pilus 2a assembly.
Group B Streptococcus pili are covalently linked structures assembled via a sortase-catalyzed transpeptidation mechanism involving specific residues and motifs. A sequence element containing a conserved glutamic acid, called the E-box, has been described to be involved in pilus formation. Although it is known that the glutamic acid is involved in stabilizing the internal isopeptide bonds, its role in pilus assembly still needs to be investigated. Using site-specific mutagenesis and complementation studies of knockout strains, we found that the E-box glutamic residue of the backbone and the major ancillary proteins is essential for pilus protein polymerization. NMR analysis revealed that the mutation of this residue seriously affected the folding of the protein. By contrast, the mutation of the lysine involved in the same isopeptide bond did not engender a structural destabilization, and the native fold was preserved. Moreover, molecular dynamics simulations on the E-box-containing domain of the backbone protein showed that the E-box glutamic acid is necessary to maintain the appropriate dryness of the domain core and that its mutation favors an unfolded state. The data provide the first direct evidence that the E-box has an additional and key role in maintaining the correct protein fold independently of isopeptide bond formation.


[Renal complications after general surgical operations (author's transl)].
Oliguria, an easily recognizable symptom of postoperative acute renal failure, is analyzed schematically in terms of various diagnostic aspects and a pragmatic therapeutic procedure. Differentiation among pre-, intra-, and postrenal disturbances is important. Acute renal failure caused by simultaneous and often severe insufficiency of other organs, especially in combination with septicemia, still has a bad prognosis. Prophylaxis in the form of adequate volume substitution and shock therapy is urgent in each case.


Purification, crystallization and preliminary X-ray analysis of the peptidoglycan N-acetylglucosamine deacetylase BC1960 from Bacillus cereus in the presence of its substrate (GlcNAc)6.
The peptidoglycan N-acetylglucosamine (GlcNAc) deacetylase BC1960 from Bacillus cereus (EC 126.96.36.199), an enzyme consisting of 275 amino acids, was crystallized in the presence of its substrate (GlcNAc)(6). The crystals belonged to the tetragonal space group P4(1)2(1)2, with unit-cell parameters a = b = 92.7, c = 242.9 A and four molecules in the asymmetric unit. A complete data set was collected at 100 K to a resolution of 2.38 A using synchrotron radiation.


One-year functional magnetic resonance imaging follow-up study of neural activation during the recall of unresolved negative life events in borderline personality disorder.
Recall of adverse life events under brain imaging conditions has been shown to coincide with activation of limbic and prefrontal brain areas in borderline personality disorder (BPD). We investigate changes of functional magnetic resonance imaging (fMRI) activation patterns during the recall of unresolved adverse life events (ULE) over 1 year. Thirteen female BPD patients participated in the study. During fMRI measurement subjects recalled ULE and negative but resolved life events (RLE) after individual cue words to stimulate autobiographical memory retrieval. Subjective intensity of emotional and sensoric experiences during recall was assessed as well as standardized measures of psychopathology. A 2x2 factorial analysis of fMRI data (Deltat1/t2xDeltaULE/RLE) revealed major right more than left differences of activation (i.e. t1>t2) of the posterior more than anterior cingulate, superior temporal lobes, insula, and right middle and superior frontal lobes (second-level analysis, t=3.0, puncorrected=0.003). The opposite contrast (Deltat2/t1xDeltaULE/RLE) did not reveal any differences. We did not find changes of emotional or sensoric qualities during recall (ULE versus RLE) or of psychopathology measures over the 1-year period. Although subjective and clinical data did not change within 1 year, we observed a substantial decrease of temporo-frontal activation during the recall of ULE from t1 to t2. If future research confirms these findings, the question arises whether the decrease of neural activation precedes clinical improvement in BPD.


Thoracic surgery in the real world: does surgical specialty affect outcomes in patients having general thoracic operations?
Most general thoracic operations in the United States are performed by general surgeons. Results obtained by those identified as general surgeons are often compared with those identified as thoracic surgeons. We interrogated the American College of Surgeons National Surgical Quality Improvement Project database over a 5-year period to compare outcomes in patients who underwent similar operations by surgeons identified as either thoracic surgeons or general surgeons. We employed propensity-score matching to minimize confounding when estimating the effect of surgeon identity on postoperative outcomes. During the study period, thoracic surgeons performed 3,263 major pulmonary or esophageal operations, and general surgeons performed 15,057 similar operations. Compared with patients operated on by general surgeons, patients operated on by thoracic surgeons had significant excess multivariate comorbidities, including insulin-dependent diabetes mellitus, chronic obstructive pulmonary disease, concurrent pneumonia, congestive heart failure, previous cardiac surgery, dialysis-dependent renal failure, disseminated cancer, prior sepsis, and previous operation within 30 days. Likewise, patients in highest risk categories had operations performed by thoracic surgeons more commonly than by general surgeons. Unadjusted comparisons for mortality and serious morbidity showed significantly worse mortality and pulmonary complications in patients operated on by thoracic surgeons. However, with propensity matching according to surgeon type, thoracic surgeons had significantly fewer serious adverse outcomes compared with general surgeons, and this decreased morbidity occurred in a higher risk cohort. Our results show that patients operated on by thoracic surgeons have higher acuity compared with patients operated on by general surgeons. When patients are matched for comorbidities and serious preoperative risk factors, thoracic surgeons have improved outcomes, especially with regard to infectious complications and composite morbidity.


Targeting inflammation and wound healing by opioids.
Opioid receptors are expressed on peripheral sensory nerve endings, cutaneous cells, and immune cells; and local application of opioids is used for the treatment of inflammatory pain in arthritis, burns, skin grafts, and chronic wounds. However, peripherally active opioids can also directly modulate the inflammatory process and wound healing. Here, we discuss the underlying mechanisms of opioid action and the conceivable therapeutic approaches for opioid treatment, as investigated in experimental and clinical studies. A large number of in vitro experiments and animal model investigations have produced evidence that peripherally active opioids can reduce plasma extravasation, vasodilation, proinflammatory neuropeptides, immune mediators, and tissue destruction. In contrast to currently available anti-inflammatory agents, opioids have not demonstrated organ toxicity, thus making them interesting candidates for drug development. Few clinical studies have tapped into this potential to date.


Nonpeptide glycoprotein IIb/IIIa inhibitors: substituted quinazolinediones and quinazolinones as potent fibrinogen receptor antagonists.
The synthesis and biological activity of a series of 3,6-substituted quinazolinediones and quinazolinones are described. The potent activity of these compounds as platelet aggregation inhibitors demonstrates the utility of these structures as central templates for nonpeptide RGD mimics.


Impact of temperature and storage duration on the chemical and odor quality of military packaged water in polyethylene terephthalate bottles.
The impact of temperature and storage time on military packaged water (MPW) quality was examined at four temperatures (23.0 °C to 60.0 °C) for 120 days. Polyethylene terephthalate (PET) bottles were filled in California and Afghanistan with unbuffered water treated by reverse osmosis. The US military's water pH long-term potability standard was exceeded, and US Food and Drug Administration (USFDA) and US Environmental Protection Agency (USEPA) drinking water pH and odor intensity limits were also exceeded. During a 70 day exposure period, Port Hueneme MPW total organic carbon and total trihalomethane levels increased from < 0.25mg/L to 2.0 ± 0.0mg/L and <0.05 μg/L to 51.5 ± 2.1 μg/L, respectively. PET released organic contaminants into MPW and residual disinfectant generated trihalomethane contaminants. After 14 days at 37.7 °C and 60.0 °C, Afghanistan MPW threshold odor number values were 8.0 and 8.6, respectively. Total organic carbon concentration only increased with exposure duration at 60.0 °C. Acetaldehyde and formaldehyde contaminants were not detected likely due to the high method detection limits applied in this study. Phthalate contaminants detected and their maximum levels were butylbenzylphthalate (BBP) 0.43 μg/L, di-n-butylphthalate (DnBP) 0.38 μg/L, di(2-ethylhexyl)phthalate (DEHP) 0.6 μg/L, and diethylphthalate (DEP) 0.32 μg/L. Antimony was only detected in 60.0 °C Afghanistan MPW on Day 28 and beyond, and its maximum concentration was 3.6 ± 0.3 μg/L. No antimony was found in bottles exposed to lesser temperatures. Environmental health, PET synthesis and bottle manufacturers, and bottle users can integrate results of this work to improve health protective decisions and doctrine.


Clinical outcome and risk factors for mortality in Chinese patients with diabetes on peritoneal dialysis: a 5-year clinical cohort study.
We evaluated clinical outcome and risk factors affecting survival in patients with diabetes on continuous ambulatory peritoneal dialysis (CAPD) in Southern China. This longitudinal cohort study enrolled all incident patients who used CAPD as their first renal replacement therapy modality in our center from January 2006 to December 2009 and who were followed until December 2011. Clinical outcomes were compared and risk factors for mortality in patients with diabetes were analyzed. Of 809 incident CAPD patients, 189 (23.4%) had diabetes. Death-censored technique survival showed no significant difference between patients with and without diabetes (p=0.271). The 1-, 2-, 3- and 5-year patient survival rates were 90%, 72%, 63% and 36% in patients with diabetes and 95%, 92%, 87% and 73% in patients without diabetes, respectively (p=0.000). Presence of cardiovascular disease (CVD) [hazard ratio (HR) 2.130, 95% confidence interval (CI) 1.199-3.786, p=0.010], advanced age (HR 1.042, 95% CI 1.008-1.078, p=0.014), higher glycated hemoglobin (HR 1.309, 95% CI 1.045-1.640, p=0.019), lower hemoglobin (HR 0.978, 95% CI 0.964-0.992, p=0.003) and lower serum albumin (HR 0.924, 95% CI 0.876-0.976, p=0.004) at the initiation of CAPD were independent risk factors of mortality in CAPD patients with diabetes. Technique survival in CAPD patients with diabetes was similar to those without diabetes. Although patients with diabetes had higher risk of mortality, the patient survival in our study seems to be improved compared with most other reports. Older age, presence of CVD, hyperglycemia, anemia and hypoalbuminemia at the commencement of CAPD affected survival in patients with diabetes.


Prophylactic neck surgery for second-generation multiple endocrine neoplasia type 2B.
There is no evidence-based guidance on the extent of prophylactic neck surgery for second-generation multiple endocrine neoplasia type 2B (MEN 2B), a newly emerging entity in the molecular era. In this investigation of MEN 2B children who inherited the M918T RET germline mutation from a phenotypically affected MEN 2B parent, 6 MEN 2B children (4 girls and 2 boys) from 5 MEN 2B parents (4 mothers and 1 father) were identified. None of the 6 second-generation MEN 2B children who had preoperative calcitonin serum levels between 2 and 105 pg/mL and underwent prophylactic total thyroidectomy before the age of 4 years after receiving a positive RET gene test harbored node metastases. There was no recurrent laryngeal nerve palsy or postoperative hypoparathyroidism. Within the limitations of this study, total thyroidectomy alone is adequate therapy for second-generation MEN 2B children aged 1-4 years old with preoperative calcitonin serum levels ≤100 pg/mL.


Menopausal Hormone Therapy in Older Women: Examining the Current Balance of Evidence.
Menopause occurs in all women. During the menopause transition, 80% of women experience vasomotor symptoms that can last an average of 7-10 years or longer, sometimes into the seventh and eighth decades of life. Understanding how to manage vasomotor symptoms (VMS) in older menopausal women is important since these symptoms can negatively impact quality of life. This review provides a practical guide on how to approach VMS treatment either with menopausal hormone therapy or non-hormone options. When initiating, as well as continuing hormone therapy, the factors clinicians should consider as they weigh risks and benefits include assessing a woman's risks related to cardiovascular disease, breast cancer, and osteoporosis. Utilizing a shared decision-making approach in regard to menopausal symptom management should aim to support women and help them maintain health and quality of life.


Core proteome mediated therapeutic target mining and multi-epitope vaccine design for Helicobacter pylori.
Helicobacter pylori is a Gram-negative spiral-shaped bacterium that infects half of the human population worldwide and causes chronic inflammation. In the present study, we used the art of computational biology for therapeutic drug targets identification and a multi-epitope vaccine against multi-strains of H. pylori. For drug target identification, we used different tools and softwares to identify human non-homologous but pathogen essential proteins, with virulent properties and involved in unique metabolic pathways of H. pylori. For this purpose, the core proteome of 84 strains of H. pylori was retrieved from EDGAR 2.3 database. There were 59,808 proteins sequences in these strains. Duplicates and paralogous protein sequence removal was followed by human non-homologous protein miningPathogen essential and virulent proteins were subjected to pathway analysis Subcellular localization of the virulent proteins was predicted and druggability was also checked, leading to 30 druggable targets based on their similarity with the approved drug targets in Drugbank. For immunoinformatics analysis, we selected two outer membrane proteins (HPAKL86_RS06305 and HPSNT_RS00950) and subjected to determined immunogenic B and T-Cell epitopes. The B and T-Cell overlapped epitopes were selected to design 9 different vaccine constructs by using linkers and adjuvants. Least allergenic and most antigenic construct (C-8) was selected as a promiscuous vaccine to elicit host immune response. Cloning and in silico expression of the constructed vaccine (C-8) was done to produce a clone having the desired (gene) vaccine construct. In conclusion, the prioritized therapeutic targets for 84 strains of H.pylori will be useful for future therapy design. Vaccine design may also prove useful in the quest for targeting multi-strains of H. pylori in patients.


Discrimination and disability: Types of discrimination and association with trust, self-efficacy and life satisfaction among older Australians.
To examine the prevalence, context and types of discrimination reported by older Australians (aged 55 years and over) and associations between outcomes (trust, self-efficacy and life satisfaction) and exposure to discrimination. The 2014 General Social Survey was used to measure discrimination. Multivariable logistic regression was used to examine associations between levels of trust, self-efficacy and life satisfaction and exposure to discrimination. A sizeable minority of older Australians with a disability reported discrimination (15%), with higher exposure for those with more severe or multiple disabilities. In addition to disability, age and nationality, race or ethnic group were cited as reasons for discrimination. Discrimination was reported across a variety of contexts, including everyday social interactions. Lower levels of trust, self-efficacy and life satisfaction were associated with exposure to disability discrimination. Focusing on disability discrimination alone underestimates the level of exposure to discrimination. Discrimination may reinforce social exclusion by reducing trust and self-efficacy in familial and community contexts.


Ultrafractionation does not improve the results of radiotherapy in radioresistant murine DDL1 lymphoma.
Low-dose hyperradiosensitivity (HRS), i.e., a relatively higher efficacy of doses < or = 0.5 Gy compared to doses > 1 Gy, has been shown in a number of tumor cell lines in vitro. Therefore ultrafractionated irradiation, i.e., application of very low doses per fraction, has been proposed to improve the effects of radiotherapy. The present study investigates ultrafractionation (UF) in radioresistant murine DDL1 T-cell lymphoma in mice. UF was performed with 0.4 Gy per fraction, three fractions per day at 7 days per week, and conventional fractionation (CF) with 1.68 Gy per fraction, one fraction per day at 5 days per week. Tumor growth delay was evaluated for 2, 4 and 6 weeks of irradiation as time that tumors needed to reach fivefold the starting volume (GD(V5)). GD(V5) was not significantly different between UF and CF. The composite median relative GD(V5) calculated for all tumors irradiated in the present study was 1.00 [95% confidence interval 0.99; 1.08] in the CF and 0.99 [0.92; 1.01] in the UF arm (p = 0.24). UF was not more efficient than CF in DDL1 tumors. Taken together with previous experiments on human A7 glioblastoma, which showed a negative effect of UF on local tumor control, the preclinical data obtained in this laboratory so far do not support the use of ultrafractionated schedules in radiotherapy.


[Readmission in a Maternity Hospital for early mother-child relationship disorders].
We report the original experience of admission in a post-delivery care unit, of a mother and her one-month-old child, for the treatment of post-delivery depression, in association with mother-child relational disorders. In this emergency situation, a maternity hospital team was involved in a maternity care.


Gene expression profiling in subcutaneous, visceral and epigastric adipose tissues of patients with extreme obesity.
The goal of the present study was to identify differences in gene expression between SAT, VAT and EAT depots in Class III severely obese individuals. Human subcutaneous (SAT) and visceral (VAT) adipose tissues exhibit differential gene expression profiles. There is little information, however, about the other proximal white adipose tissue, epigastric (EAT), in terms of its function and contribution to metabolism. Using RNA from adipose biospecimens obtained from Class III severely obese patients undergoing open Roux-en-Y gastric bypass surgery, we compared gene expression profiles between SAT, VAT and EAT, using microarrays validated by real-time quantitative PCR. The three depots were found to share 1907 genes. VAT had the greatest number of genes (66) expressed exclusively in this depot, followed by SAT (23), and then EAT (14). Moreover, VAT shared more genes with EAT (65) than with SAT (38). Further analyses using ratios of SAT/EAT, VAT/EAT and SAT/VAT identified specific as well as overlapping networks and pathways of genes representing dermatological diseases, inflammation, cell cycle and growth, cancer and development. Targeted analysis of genes, having a role in adipose tissue development and function, revealed that Peroxisome proliferator-activated receptor Gamma Coactivator 1-alpha (PGC1-α) that regulates the precursor of the hormone Irisin (FNCD5) were abundantly expressed in all three fat depots, along with fibroblast growth factors (FGF) FGF1, FGF7 and FGF10, whereas, FGF19 and FGF21 were undetectable. These data indicate that EAT has more in common with VAT, suggesting similar metabolic potential. The human epigastric adipose depot could have a significant functional role in metabolic diseases and should be further investigated.


Lack of interference by sorbitol with aminopyrine breath test.
The effect of sorbitol on the aminopyrine breath test was investigated in 13 patients with various liver diseases given a bolus dose of sorbitol 20 mg.kg-1 i.v. 30 min after 14C-aminopyrine and 13 patients without the sorbitol bolus who also underwent an aminopyrine breath test. The time course of 14CO2 exhalation after the bolus of sorbitol did not differ from that in the control group.


Loss of pigment-laden stellate cells: a severe alteration of the isocortex in juvenile neuronal ceroid-lipofuscinosis.
Juvenile neuronal ceroid-lipofuscinosis is associated with a moderate numerical decrease of isocortical neurons. From Nissl preparations, it is not apparent, whether this neuronal rarefication occurs at random or affects specific types of cortical neurons. Lipopigment preparations facilitate the distinction between pyramidal and stellate cells. In juvenile neuronal ceroid-lipofuscinosis, they reveal an almost complete to total loss of small pigment-laden stellate cells. This type of local circuit neurons, scattered throughout the corpuscular and pyramidal layer in varying numbers and patterns of distribution, is common to all isocortical regions. Its pronounced and selective vulnerability in this lysosomal disease may be causally related to the marked functional impairment of the brain.


Evolving locomotion for a 12-DOF quadruped robot in simulated environments.
We demonstrate the power of evolutionary robotics (ER) by comparing to a more traditional approach its performance and cost on the task of simulated robot locomotion. A novel quadruped robot is introduced, the legs of which - each having three non-coplanar degrees of freedom - are very maneuverable. Using a simplistic control architecture and a physics simulation of the robot, gaits are designed both by hand and using a highly parallel evolutionary algorithm (EA). It is found that the EA produces, in a small fraction of the time that takes to design by hand, gaits that travel at two to four times the speed of the hand-designed one. The flexibility of this approach is demonstrated by applying it across a range of differently configured simulators.


Partitioning and matrix-specific toxicity of bifenthrin among sediments and leaf-sourced organic matter.
Synthetic pyrethroids readily partition from the aqueous to the solid phase in aquatic systems. Previous work has focused on pyrethroid partitioning to sediment matrices. Within many aquatic systems, however, other carbon-containing materials are present and can be critically important to certain invertebrate species and ecosystem functioning. For example, some invertebrates readily process leaf material, and these processes may represent an additional route of contaminant exposure. To our knowledge, estimates for partitioning of pyrethroids to these nondissolved organic matter matrices and associated toxicity have not been examined. The objectives of the present study were to examine variation in organic carbon (OC)-based partition coefficient (K(OC)) among three size fractions of particulate organic matter from sugar maple (Acer saccharum) leaf litter and sediments for the pyrethroid insecticide bifenthrin and to examine variation in toxicity to Hyalella azteca among bifenthrin-bound organic matter matrices and sediment. Log K(OC) of [(14)C]bifenthrin was greatest within sediment (6.63+/-0.23; mean +/- standard deviation throughout) and lowest in coarse particulate leaf material (4.86+/-0.03). The H. azteca median lethal concentration was 0.07, 0.11, and 0.15 microg/g OC for leaf material, sediment, and a 50% mix of leaf and sediment, respectively. Nonoverlapping 95% confidence intervals occurred between the leaf treatment and the leaf-sediment treatment. This pattern was supported in an additional experiment, and at 0.22 microg/g OC, H. azteca survival was greater in the leaf-sediment mixture than in sediment or in leaf material alone (F=29.5, p<0.0001). In systems that contain sediment and leaf material, both greater partitioning of bifenthrin to the sediment fraction and preferential use of leaf substrates may drive H. azteca survival.


Nanoscale Infrared Spectroscopy Identifies Parallel to Antiparallel β-Sheet Transformation of Aβ Fibrils.
Spontaneous aggregation of amyloid beta (Aβ) proteins leading to the formation of oligomers and eventually into fibrils has been identified as a key pathological signature of Alzheimer's disease. The structure of late-stage aggregates have been studied in depth by conventional structural biology techniques, including nuclear magnetic resonance, X-ray crystallography, and infrared spectroscopy; however, the structure of early-stage aggregates is less known due to their transient nature. As a result, the structural evolution of amyloid aggregates from early oligomers to mature fibrils is still not fully understood. Here, we have applied atomic force microscopy-infrared nanospectroscopy to investigate the aggregation of Aβ 16-22, which spans the amyloidogenic core of the Aβ peptide. Our results demonstrate that Aβ 16-22 involves a structural transition from oligomers with parallel β-sheets to antiparallel fibrils through disordered and possibly helical intermediate fibril structures, contrary to the known aggregation pathway of full-length Aβ.


Sickle cell disease subjects and mouse models have elevated nitrite and cGMP levels in blood compartments.
The hypothesis of decreased nitric oxide (NO) bioavailability in sickle cell disease (SCD) proposes that multiple factors leading to decreased NO production and increased consumption contributes to vaso-occlusion, pulmonary hypertension, and pain. The anion nitrite is central to NO physiology as it is an end product of NO metabolism and serves as a reservoir for NO formation. However, there is little data on nitrite levels in SCD patients and its relationship to pain phenotype. We measured nitrite in SCD subjects and examined its relationship to SCD pain. In SCD subjects, median whole blood, red blood cell and plasma nitrite levels were higher than in controls, and were not associated with pain burden. Similarly, Townes and BERK homozygous SCD mice had elevated blood nitrite. Additionally, in red blood cells and plasma from SCD subjects and in blood and kidney from Townes homozygous mice, levels of cyclic guanosine monophosphate (cGMP) were higher compared to controls. In vitro, hemoglobin concentration, rather than sickle hemoglobin, was responsible for nitrite metabolism rate. In vivo, inhibition of NO synthases and xanthine oxidoreductase decreased nitrite levels in homozygotes but not in control mice. Long-term nitrite treatment in SCD mice further elevated blood nitrite and cGMP, worsened anemia, decreased platelets, and did not change pain response. These data suggest that SCD in humans and animals is associated with increased nitrite/NO availability, which is unrelated to pain phenotype. These findings might explain why multiple clinical trials aimed at increasing NO availability in SCD patients failed to improve pain outcomes.


β-Arrestin-1 mediates thyrotropin-enhanced osteoblast differentiation.
Thyrotropin (TSH) activation of the TSH receptor (TSHR), a 7-transmembrane-spanning receptor (7TMR), may have osteoprotective properties by direct effects on bone. TSHR activation by TSH phosphorylates protein kinases AKT1, p38α, and ERK1/2 in some cells. We found TSH-induced phosphorylation of these kinases in 2 cell lines engineered to express TSHRs, human embryonic kidney HEK-TSHR cells and human osteoblastic U2OS-TSHR cells. In U2OS-TSHR cells, TSH up-regulated pAKT1 (7.1±0.5-fold), p38α (2.9±0.4-fold), and pERK1/2 (3.1±0.2-fold), whereas small molecule TSHR agonist C2 had no or little effect on pAKT1 (1.8±0.08-fold), p38α (1.2±0.09-fold), and pERK1/2 (1.6±0.19-fold). Furthermore, TSH increased expression of osteoblast marker genes ALPL (8.2±4.6-fold), RANKL (21±5.9-fold), and osteopontin (OPN; 17±5.3-fold), whereas C2 had little effect (ALPL, 1.7±0.5-fold; RANKL, 1.3±0.6-fold; and OPN, 2.2±0.7-fold). β-Arrestin-1 and -2 can mediate activatory signals by 7TMRs. TSH stimulated translocation of β-arrestin-1 and -2 to TSHR, whereas C2 failed to translocate either β-arrestin. Down-regulation of β-arrestin-1 by siRNA inhibited TSH-stimulated phosphorylation of ERK1/2, p38α, and AKT1, whereas down-regulation of β-arrestin-2 increased phosphorylation of AKT1 in both cell types and of ERK1/2 in HEK-TSHR cells. Knockdown of β-arrestin-1 inhibited TSH-stimulated up-regulation of mRNAs for OPN by 87 ± 1.7% and RANKL by 73 ± 2.4%, and OPN secretion by 74 ± 10%. We conclude that TSH enhances osteoblast differentiation in U2OS cells that is, in part, caused by activatory signals mediated by β-arrestin-1.


Technical error during deployment leads to vena cava filter migration and massive pulmonary embolism.
The Günther Tulip vena cava filter is a safe, effective, well-established device for pulmonary embolism prophylaxis. We report a patient in whom there was migration of the filter to the right atrium, 2 weeks after insertion, caused by a technical error during deployment. An attempt to retrieve the filter percutaneously failed, necessitating removal at open-heart surgery. The potential causes of migration are described and the lessons learned from this unusual case are outlined.


Dual-Pronged Attack: pH-Driven Membrane-Anchored NIR Dual-Type Nano-Photosensitizer Excites Immunogenic Pyroptosis and Sequester Immune Checkpoint for Enhanced Prostate Cancer Photo-Immunotherapy.
Prostate cancer (PCa) is a frustrating immunogenic "cold" tumor and generally receives unsatisfied immunotherapy outcomes in the clinic. Pyroptosis is an excellent immunogenic cell death form that can effectively activate the antitumor immune response, promote cytotoxic T-lymphocyte infiltration, and convert tumors from "cold" to "hot." However, the in vivo application of pyroptosis drugs is seriously limited, and the upregulation of tumor PD-L1 caused by photo-immunotherapy further promotes immune escape. Herein, a new nano-photosensitizer (YBS-BMS NPs-RKC) with pH-response integrating immunogenic pyroptosis induction and immune checkpoint blockade is developed. The pH-responsive polymer equipped with the cell membrane anchoring peptide RKC is used as the carrier and further encapsulated with the near-infrared-activated semiconductor polymer photosensitizer YBS and a PD-1/PD-L1 complex small molecule inhibitor BMS-202. The pH-driven membrane-anchoring and pyroptosis activation of YBS-BMS NPs-RKC is clearly demonstrated. In vitro and in vivo studies have shown that this dual-pronged therapy stimulates a powerful antitumor immune response to suppress primary tumor progression and evokes long-term immune memory to inhibit tumor relapse and metastasis. This work provides an effective self-synergistic platform for PCa immunotherapy and a new idea for developing more biocompatible photo-controlled pyroptosis inducers.


The surgical rehabilitation of total deafness with the multichannel cochlear implant. Indications and results.
In case of total deafness the multichannel cochlear implant supplies a substantial improvement. It allows recognition of known words without lip reading, with a high percentage of good responses. Clinical and phoniatric results are reported in 21 cases of implanted patients.


An RGB-emitting molecular cocktail for the detection of bacterial fingerprints.
Accumulating evidence indicates that colonized microbes play a crucial role in regulating health and disease in the human body. Detecting microbes should be essential for understanding the relationship between microbes and diseases, as well as increasing our ability to detect diseases. Here, a combined metabolic labeling strategy was developed to identify different bacterial species and microbiota by the use of three different fluorescent metabolite derivatives emitting red, green, and blue (RGB) fluorescence. Upon co-incubation with microbes, these fluorescent metabolite derivatives are incorporated into bacteria, generating unique true-color fingerprints for different bacterial species and different microbiota. A portable spectrometer was also fabricated to automate the colorimetric analysis in combination with a smartphone to conveniently identify different bacterial species and microbiota. Herein, the effectiveness of this system was demonstrated by the identification of certain bacterial species and microbiota in mice with different diseases, such as skin infections and bacteremia. By analyzing the microbiota fingerprints of saliva samples from clinical patients and healthy people, this system was proved to precisely distinguish oral squamous cell carcinoma (OSCC, n = 29) samples from precancerous (n = 10) and healthy (n = 5) samples.


2D-Material-Integrated Micromachines: Competing Propulsion Strategy and Enhanced Bacterial Disinfection.
2D transition-metal-dichalcogenide materials, such as molybdenum disulfide (MoS2 ) have received immense interest owing to their remarkable structure-endowed electronic, catalytic, and mechanical properties for applications in optoelectronics, energy storage, and wearable devices. However, 2D materials have been rarely explored in the field of micro/nanomachines, motors, and robots. Here, MoS2 with anatase TiO2 is successfully integrated into an original one-side-open hollow micromachine, which demonstrates increased light absorption of TiO2 -based micromachines to the visible region and the first observed motion acceleration in response to ionic media. Both experimentation and theoretical analysis suggest the unique type-II bandgap alignment of MoS2 /TiO2 heterojunction that accounts for the observed unique locomotion owing to a competing propulsion mechanism. Furthermore, by leveraging the chemical properties of MoS2 /TiO2 , the micromachines achieve sunlight-powered water disinfection with 99.999% Escherichia coli lysed in an hour. This research suggests abundant opportunities offered by 2D materials in the creation of a new class of micro/nanomachines and robots.


A malware detection system using a hybrid approach of multi-heads attention-based control flow traces and image visualization.
Android is the most widely used mobile platform, making it a prime target for malicious attacks. Therefore, it is imperative to effectively circumvent these attacks. Recently, machine learning has been a promising solution for malware detection, which relies on distinguishing features. While machine learning-based malware scanners have a large number of features, adversaries can avoid detection by using feature-related expertise. Therefore, one of the main tasks of the Android security industry is to consistently propose cutting-edge features that can detect suspicious activity. This study presents a novel feature representation approach for malware detection that combines API-Call Graphs (ACGs) with byte-level image representation. First, the reverse engineering procedure is used to obtain the Java programming codes and Dalvik Executable (DEX) file from Android Package Kit (APK). Second, to depict Android apps with high-level features, we develop ACGs by mining API-Calls and API sequences from Control Flow Graph (CFG). The ACGs can act as a digital fingerprint of the actions taken by Android apps. Next, the multi-head attention-based transfer learning method is used to extract trained features vector from ACGs. Third, the DEX file is converted to a malware image, and the texture features are extracted and highlighted using a combination of FAST (Features from Accelerated Segment Test) and BRIEF (Binary Robust Independent Elementary Features). Finally, the ACGs and texture features are combined for effective malware detection and classification. The proposed method uses a customized dataset prepared from the CIC-InvesAndMal2019 dataset and outperforms state-of-the-art methods with 99.27% accuracy.


Novel Zn(II) complexes with non-steroidal anti-inflammatory ligand, flufenamic acid: Characterization, topoisomerase I inhibition activity, DNA and HSA binding studies.
A series of new Zn(II) complexes with flufenamic acid (flu) has been synthesized, namely [Zn3(dmso)2(flu)6] (1), [Zn3(flu)6(py)2] (2), [Zn(flu)2(tmen)] (3), [ZnCl(flu)(neo)] (4), and [Zn(cyclam)(flu)2] (5), where py=pyridine, tmen=N,N,N',N'-Tetramethylethylene diamine, neo=2,9-Dimethyl-1,10-phenanthroline and cyclam=1,4,8,11-Tetraazacyclotetradecane. These complexes have been characterized by infrared spectroscopy, single-crystal X-ray structure analysis, elemental and thermal analysis. All complexes contain deprotonated flufenamic acid coordinated via carboxylato group to zinc atoms, but their structures differ in the carboxylato binding mode, the coordination number of the central atom, the shape of the coordination polyhedra and the resultant supramolecular structures. Furthermore, an interaction of complexes with calf-thymus DNA (CT DNA) and human serum albumin (HSA) has been investigated by spectroscopic techniques. Moreover, the complexes 1 and 2 inhibit the catalytic activity of topoisomerase I at 60μM.


Bone scintigraphy may help differentiate bone sclerotic lesions from osteoblastic metastases in tuberous sclerosis patients with concomitant pulmonary adenocarcinoma.
Tuberous sclerosis (TS) is a multisystem disorder characterized by widespread hamartomas in multiple organs, including the skeleton. We present a case of bone involvement in a patient with TS and concomitant pulmonary adenocarcinoma. Bone scintigraphy is useful in distinguishing the TS bone lesions from osteoblastic metastases.


Intra-operative culture swabs in acute appendicitis: a waste of resources.
Antibiotics gained a place in the management of acute appendicitis when the bacterial aetiology was demonstrated. Culture swabs were obtained routinely during appendicectomies to guide antibiotic use. Although current antimicrobial therapy use has become prophylactic, empirical and broad spectrum, this age-old practice still remains. Our study questions the value of this traditional practice. All adult and paediatric patients undergoing emergency appendicectomy over three years were retrospectively reviewed. Microbiology and appendix histology reports were retrieved. Occurrence of infective post-operative morbidity was recorded via hospital notes. A total of 652 appendectomies (age 1 month to 81 years, median 20 years) were performed in a 36 month period. Four hundred and thirty-five/six hundred and fifty-two (66.7%) had intra-operative swabs taken. One hundred and forty/four hundred and thirty-five (32%) revealed presence ofa pathogens. One hundred and twenty-two/four hundred and thirty-five (28%) were sensitive to broad spectrum empirical antibiotics and only 18/435 (4.1%) cultured resistant strains. Forty-two/six-hundred and fifty-two (6.4%) patients had postoperative infective complications. Twenty-nine/forty-two (68%) had a different organism responsible for this complication. The highest proportion of positive cultures and post-operative infective complications was observed in the extremes of ages (< 10 and > 50 years) and in gangrenous appendicitis. A majority of intra-operative swabs were negative or isolated commensal flora. Pathogens causing postoperative morbidity were frequently different from those isolated intra-operatively. None of the patients had a change of management based on the swab results. Hence routine intra-peritoneal swabs remains of little clinical value.


The contribution of abiotic processes to buried litter decomposition in the northern Chihuahuan desert.
Creosobebush (Larrea tridentata) fine litter was treated with either the general biocide HgCl2 and CuSO4 or water (controls) and buried 5 cm beneath the soil surface in the northern Chihuahuan Desert. The treated litter showed significantly less mass loss than controls during the three month summer-autumn field study; controls lost about 20% of the original mass while treated litter lost less than 2%. In addition, the total nitrogen content of the control litter increased from an initial concentration of about 14.08 g kg-1 to 17.62 g kg-1 dry weight by the end of the study, while treated litter nitrogen content decreased to 13.30 g kg-1. Results suggest abiotic processes other than leaching have little effect on the decomposition of buried litter in this environment.


Detection of gentoxicity of benzidine and its derivatives with the Escherichia coli DJ 702 lacZ reversion mutagenicity assay.
The feasibility of Escherichia coli DJ 702 lacZ mutagenicity assay to detect genotoxicity of benzidine and its derivatives was evaluated. DJ 702 strain was grown overnight at 30 degrees C in Luria-Bertani (LB) medium containing some components, such as chloramphenicol, ampicillin, delta-aminolevulinic acid, isopropyl-beta-d-thiogalactoside, and trace element mix. The mixtures of a bacterial culture and tested chemical at indicated doses were incubated at 30 degrees C for 30 min. Subsequently, 2 ml of molten top agar was added and the resulting mixtures were immediately poured onto a minimal lactose (ML) plate. Plates were incubated at 30 degrees C for 48 h. The number of colonies was determined by visual scoring. In this study, results showed that all the tested chemicals were mutagenic to DJ 702 strain. E. coli lac mutagenicity assay using DJ 702 strain can detect the mutagenicity of benzidine and its derivatives. We detected the mutagenicity of benzidine and its derivatives in E. coli lac mutagenicity assay using DJ 702, indicating that this assay may be used to detect benzidine and its derivatives in a powerful, sensitive, and convenient mutagenesis assay.


MRI of bone metastases.
Some knowledge of MR theory is required to be able to achieve high contrast between bone metastases and normal marrow. Three factors are used in MR to diagnose bone metastases; fat-water distribution, artifacts induced by bone trabeculae, and uptake of contrast medium. Using MR-histological correlations based on specimens of the lumbar spine, and studies of patients, we explain the advantages and limitations of sequences studying fat and water (spin-echo T1, STIR, in- and out-of-phase gradient echo, fat presaturation), bone trabeculae (gradient echo with long TE), and the injection of contrast medium.


Pseudo-pacemaker syndrome following inadvertent fast pathway ablation for atrioventricular nodal reentrant tachycardia.
Atrioventricular nodal reentrant tachycardia that is refractory to drug treatment has recently been treated with radiofrequency catheter ablation. In this case report we describe a patient with atrioventricular nodal reentrant tachycardia in whom radiofrequency ablation of slow pathway was attempted, with inadvertent damage to the fast pathway. The patient developed marked first-degree atrioventricular block associated with symptoms mimicking pacemaker syndrome.


18F-FDG PET/CT in the diagnosis of Takayasu arteritis: A case report.
The early clinical symptoms of Takayasu arteritis (TAK) are nonspecific and often lead to misdiagnosis or delay in diagnosis. And by the time morphological changes are observed on the images, the disease is in an advanced stage and irreversible vascular injuries has occurred. Therefore, early correct diagnosis and timely systemic anti-inflammatory treatment can effectively improve the clinical situation. Conventional imaging provides only changes in vascular structure and provides little information on inflammatory activity. Here we report the PET/CT imaging presentation of 18F-deoxyglucose (18F-FDG) in a patient with TAK, a 58-year-old patient with known TAK whose disease clustered many non-specific features, and highlight the value of PET/CT in the diagnosis and management of patients with early or atypical clinical presentation of TAK.