Protease resistant protein cellular isoform (PrP(c)) as a biomarker: clues into the pathogenesis of HAND.
HIV infection and HIV neurocognitive impairment are major global health problems. The prevalence of HIV associated neurocognitive disorders (HAND) is increasing as people with HIV are living longer due to the success of antiretroviral therapies. Our laboratory identified the soluble form of (sPrP(c)), the cellular non-pathogenic isoform of the prion protein, as a biomarker of HAND. In this review we discuss the published data addressing PrP(c) biology in normal conditions and pathologies, as well as the mechanisms of sPrP(c) shedding and secretion. Lastly, we discuss our studies that demonstrated that sPrP(c) is a biomarker of neurocognitive impairment in the HIV infected population.


Suppression of induced beta-galactosidase synthesis by cysteamine and its reversion by gamma-irradiation in the presence of ascorbate.
The induced synthesis of beta-galactosidase in E. coli was found to be inhibited by cysteamine. This inhibitory effect of the SH compound was antagonized by the addition of ascorbate followed by gamma-irradiation with relatively low doses. The cAMP level which, it has been suggested, plays a role in the radioprotective action of cysteamine, is stabilized by ascorbate against changes induced by irradiation.


Relative contributions of protein sulfhydryl loss and lipid peroxidation to allyl alcohol-induced cytotoxicity in isolated rat hepatocytes.
The time course of allyl alcohol-induced toxicity was studied in freshly isolated rat hepatocytes. The sequence of events was as follows: an initial, rapid depletion of glutathione (GSH), a subsequent increase in malondialdehyde (MDA) and decrease in protein sulfhydryl groups (PSH), and the eventual loss of membrane integrity. The sulfhydryl compounds, N-acetylcysteine and dithiothreitol, markedly delayed the depletion of GSH, prevented significant loss of PSH, and protected the cells against viability loss. In contrast, the antioxidants, butylated hydroxytoluene and Trolox C, and the iron-chelating agent, deferoxamine, suppressed allyl alcohol-induced MDA production without affecting the depletion of cellular thiols or the loss of viability. The results suggest that the inactivation of protein thiol groups is critical for allyl alcohol toxicity whereas lipid peroxidation is not essential to the toxic process.


Confidentiality & the Risk of Genetic Discrimination: What Surgeons Need to Know.
In the past decade, laws have been passed to provide legal protections against genetic discrimination. Many members of the public and medical providers are unaware of the legislation, and concerns about genetic privacy can prevent delivery of optimal medical care. Patient health information, including genetic testing and family history, is protected under the Health Insurance Portability and Accountability Act and the Genetic Information Nondiscrimination Act. Additional protections are granted through the Americans with Disabilities Act, state laws, and the Affordable Care Act. Communicating a genetic test result back to a patient is important for medical management decisions and family members.


Influence of seasonal adaptation on the distribution of cytochemically detectable endogenous calcium in synaptic terminals of the optic tectum of crucian carp (Carassius carassius L.).
Crucian carps were seasonally adapted to high (23 degrees C) or low (4 degrees C) temperatures and synaptic regions in the optic tectum were analyzed by means of energy-filtering transmission electron microscopy (EFTEM). The amount of cytochemically detectable endogenous calcium in synaptic clefts was quantified by means of image analysis and the amount of glycogen granules in synaptic regions was assessed. In cold-adapted fish, glycogen is increased, especially in glial cells, while the calcium-containing precipitates are reduced. This is interpreted as a characteristic feature of inactive synapses, in which glycogen accumulates and in which the calcium turnover is slowed down. Short-term thermal stress did not influence the amount of calcium or glycogen.


Interinstitutional patient transfers between rapid chemotherapy cycles were feasible to utilize proton beam therapy for pediatric Ewing sarcoma family of tumors.
To assess the feasibility of transferring to the University of Tsukuba Hospital for proton beam therapy (PBT) during intensive chemotherapy in children with Ewing sarcoma family of tumors (ESFT) who had been diagnosed and started their first-line treatment at prefectural or regional centers for pediatric oncology. The treatment of ESFT relies on a multidisciplinary approach using intensive neoadjuvant and adjuvant chemotherapies with surgery and radiotherapy. Multi-agent chemotherapy comprising vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide (VDC-IE) is widely used for ESFT, and the interval between each course is very important for maintaining the intensity and effect of chemotherapy. Clinical information of patients who received PBT and VDC-IE between April 2009 and May 2016 was collected retrospectively. The intervals between each course of VDC-IE and adverse events were assessed. Fifteen patients were evaluated. No delays in the intervals of chemotherapy due to transfer were observed. There were no adverse events caused during/just after transfer and no increases in adverse events. The estimated 4-year overall and event-free survival rates were 94.6% and 84.8%, respectively. Although the results of efficacy are preliminary, survival rates were comparable with past studies. More experience and follow-up are required to further assess the efficacy of PBT for patients with ESFT. Multidisciplinary therapy for children with ESFT involving transfer to our hospital for PBT during VDC-IE was feasible without treatment delay or an increase in adverse events.


[ Fournier gangrene: a rare complication of multiple myeloma].
A 69-year-old male patient with multiple myeloma developed a dolent swelling of the right side of his scrotum at the time of maximal leukocyte depression after cytostatic drug therapy. Within a few hours the scrotal skin became gangrenous. After surgical debridement of the necrotic tissues and simultaneous antibiotic therapy the necrosis showed a favorable course.


MiR-130a-3p blocks Wnt signaling cascade in the triple-negative breast cancer by targeting the key players at multiple points.
Aberrant Wnt signaling cascade is a hallmark of the triple-negative breast cancer (TNBC) that is linked with the increased proliferation, invasion, and poor overall survival. many genes are post-transcriptionally regulated by microRNAs (miRNAs) therefore; it is indisputable that the dysregulation of the miRNAs is an explanation for the aberrant signaling cascades. Thus, the present study was conducted to find the putative miRNA targeting the key players of Wnt/β -catenin cascade in the TNBC. The miR-130a-3p was found as a potential regulator of the Wnt signaling cascade by applying several bioinformatic algorithms. Quantitative real-time PCR (qRT-PCR) was used to analyze the expression levels of miR-130a-3p and Wnt cascade genes in the TNBC cells. Afterward, TNBC cells were transiently transfected with the miR-130a-3p to investigate its effects on the expression of Wnt cascade genes. Subsequently, MTT, soft agar colony formation, scratch, transwell cell migration, and transwell cell invasion assays were used to determine the behavior of the TNBC cells in response to miR-130a-3p restoration. Results of the qRT-PCR showed downregulation of miR-130a-3p and upregulation of the Wnt cascade genes in the TNBC cells compared to the normal cells. Transient overexpression of miR-130a-3p decreased the expression levels of Wnt cascade genes significantly in the TNBC cells. Moreover, following the miR-130a-3p overexpression, the proliferation, anchorage-independent growth, and migration of the TNBC cells were reduced. Overall, our findings provided an evidence for the significant role of miR-130a-3p in the regulation of Wnt/β-catenin cascade, and also introduced the miR-130a-3p as a new therapeutic target for the patients with TNBC.


Visual and instrumental shade matching using CIELAB and CIEDE2000 color difference formulas.
To compare visual and instrumental shade matching performances using two shade guides and three color difference formulas. One hundred dental students (DS) volunteers (35 males and 65 females) with normal color vision participated in the study. The spectral reflectance of 4 extracted human upper central incisors (UCI) and shade tabs from Vita Classical (VC) and Vita Toothguide 3D-Master (3D) shade guides were measured using a spectroradiometer (SP) under D65 illuminant (diffuse/0° geometry) inside a viewing booth with a gray background. Color coordinates (CIE L*, a*, b*, C* and h°) were calculated according to CIE D65 illuminant and CIE 2° Standard Observer. Color coordinates of UCI were also evaluated using a dental spectrophotometer (EA - Easyshade Advance). DS used VC and 3D to visually select the best shade match for each UCI, under same experimental conditions used for the SP evaluation. Three color difference metrics (CIELAB, CIEDE2000(1:1:1) and CIEDE2000(2:1:1)) were used to calculate the best instrumental shade matching based on minimum color difference. The agreement between visual and instrumental shade matching was greater using SP (25-75%) than EA (0-25%). The percentage of best match for the visual assessment was more consistent using VC (23-55%) than 3D (19-34%). Considering the best performance (using SP and VC), the CIEDE2000(2:1:1) color difference formula showed the best estimate to the visual perception from DS. Within the limitations of this study, combining the use of SP, CIEDE2000(2:1:1) and Vita Classical shade guide most closely represented the visual perception of DS. Instrumental shade determination should be accompanied by experienced human visual assessment.


Effect of renal replacement therapy on selected arachidonic acid derivatives concentration.
Platelet activation is an important side effect of dialysis, resulted in a subsequent release of arachidonic acid (AA) from activated platelets. AA is involved in many pathologic conditions, such as inflammation, asthma, cancer, diabetes, hypertension, and the pathogenesis of kidney disease. The aim of this study was to define whether the dialysis type affects the concentration of AA derivatives in patients with chronic kidney disease. 117 patients were qualified to the study group. Based on the type of renal replacement therapy, patients were divided into the following groups: hemodialysis (HD A - before/HD B - after hemodialysis), peritoneal dialysis (PD), kidney transplant patients (TE - before/TE A - after transplantation) and conservative treatment (CT) (30; 30; 27; 30 patients, respectively). The control group consisted of 30 healthy volunteers (NK). The ELISA methods were used to measure the concentrations of TXB2, 5-HETE, 12-HETE, and 15-HETE in the blood serum. Renal replacement therapy significantly influences the concentration of TXB2 (mean ± SD [ng/mL]: HD A- 34.6 ± 9; HD B- 28.3 ± 15.2; PD- 28.3 ± 15.2; CT- 34.2 ± 8.0; TE- 36.7 ± 42.9; TE A- 27.9 ± 8.8; NK- 19.6 ± 15; p = 0.010), 5-HETE (mean ± SD [ng/mL]: HD A- 284.2 ± 428.4; HD B- 304.8 ± 516.2; PD - 530.0 ± 553.3; CT- 318.7 ± 366.0; TE- 525.6 ± 358.0; TE A - 409.8 ± 377.1; NK 838.1 ± 497.8; p < 0.001) and 15-HETE (HD A-18.1 ± 8.7; HD B- 42.2 ± 14; PD - 36.3 ± 13.8; CT- 33.7 ± 14.0; TE- 19.5 ± 10.2; TE A - 34.4 ± 16.3; NK 22.2 ± 17.8; p < 0,001). There was a significant relationship between the type of renal replacement therapy and the duration of dialysis, and the concentration of TXB2, 12-HETE acid, and 15-HETE. The type of renal replacement therapy significantly affects the concentration of AA derivatives. Peritoneal dialysis is the best method of dialysis, taking into account the concentration of arachidonic acid derivatives.


Sequence of intramolecular carbonylation and asymmetric hydrogenation reactions: highly regio- and enantioselective synthesis of medium ring tricyclic lactams.
The intramolecular cyclocarbonylation reaction with palladium-complexed dendrimers on silica is a very effective method for the regioselective synthesis of methylene 8-, 9-, and 10-membered rings. The heterogeneous dendritic catalysts are easily recovered by simple filtration and reused for up to 10 cycles with only a slight loss of activity. Asymmetric hydrogenation of the resulting unsaturated heterocycles affords optically active tricyclic lactams in excellent yields and in high enantiomeric excess. This process can tolerate a wide array of functional groups, including halide, ether, nitrile, ketone, and ester. Moreover, the variation of heteroatom on the rings does not have any influence on the efficiency and enantioselectivity of the reaction.


Single-port laparoscopic insertion of peritoneal dialysis catheters in children.
To assess the effectiveness and complication rate of laparoscopically placed peritoneal dialysis catheters using the single-port technique. This is a prospective study conducted from 2002 to 2004. Children with established renal failure requiring insertion of a peritoneal dialysis catheter were included. The insertion was performed by a single surgeon using a single-port laparoscopic technique. Partial omentectomy was performed and the catheter accurately placed in the pelvis under vision. The catheter could then be used immediately postoperatively. Twenty-two children (13F:9M) with a mean age of 9 years (range 1.0-17.5) had a peritoneal dialysis catheter inserted laparoscopically between 2002 and 2004. Mean time for insertion was 26 min (range 23-29 min). Ten (45%) catheters were used within 4 h. Early complications included a minor leak that resolved within 24 h, one exit-site infection that resolved with oral flucloxacillin, one blockage due to a fibrin clot that resolved with urokinase, and one blockage after 2 weeks due to adhesions (not omentum) that was revised. Laparoscopic insertion of a peritoneal dialysis catheter allows accurate placement of the catheter under direct vision, immediate use postoperatively with minimum morbidity, and good cosmesis. The single-port laparoscopic technique is a safe, effective and quick technique for use in children.


FDG PET for the study of primary hepatic malignancies in children.
This manuscript describes the use of FDG PET in a series of 7 children (11 scans) with primary hepatic malignancies (5 patients with hepatoblastoma, 2 patients with hepatic embryonal rhabdomyosarcoma), together with other imaging (CT and MRI), serum tumor markers, and tumor pathology. Seven children with pathologically proven hepatic malignancies underwent 11 FDG PET scans for staging (1 patient) or restaging (6 patients). Tumor uptake of FDG was assessed qualitatively and compared with biochemical and radiological findings. Abnormal uptake was demonstrated in 6 of 7 patients (10 of 11 scans). Three patients subsequently underwent partial hepatic resection, and one underwent brain biopsy, confirming in each that the abnormal uptake of FDG indicated viable tumor. In one patient, intense uptake was due to necrotizing granulomas. In one patient, images were suboptimal due to noncompliance with fasting. Primary hepatic tumors of childhood usually demonstrate increased glycolytic activity, which allows them to be imaged using PET and the tracer 18F-FDG. The technique is probably most useful for assessing response to therapy, in following AFP (alfa fetoprotein) negative cases and for detecting metastatic disease although a large series of patients will need to be studied to confirm our initial findings. Non neoplastic inflammation may also accumulate FDG and could be confused with malignancy. As these tumors are rare, prospective multicenter studies are necessary to determine the true clinical utility of FDG PET imaging in the management of children with primary hepatic malignancies.


Selenium as an interesting option for the treatment of Chagas disease: A review.
Chagas disease is one of the most prevalent tropical neglected diseases and causes high mortality and morbidity in endemic countries. Current treatments for this disease, nifurtimox and benznidazole, are ineffective in the chronic phase of the disease and produce severe adverse effects. Therefore, novel therapies are urgently required. The trace element selenium has an important role in human health, due to its antioxidant, antiinflammatory and pro-immune properties. Actually, its deficiency has been related to several diseases and supplementation with this element has been proven to be beneficial for multiple pathologies. Furthermore, the usefulness of organic-selenium compounds has been studied in many disorders, showing promising results. The aim of this review is to analyse the available literature regarding the role of selenium in Chagas disease in order to determine whether its use could be beneficial for the management of this pathology.


Structure of the carboxy-terminal LIM domain from the cysteine rich protein CRP.
The three dimensional solution structure of the carboxy terminal LIM domain of the avian Cysteine Rich Protein (CRP) has been determined by nuclear magnetic resonance spectroscopy. The domain contains two zinc atoms bound independently in CCHC (C = Cys, H = His) and CCCC modules. Both modules contain two orthogonally-arranged antiparallel beta-sheets, and the CCCC module contains an alpha-helix at its C terminus. The modules pack due to hydrophobic interactions forming a novel global fold. The structure of the C-terminal CCCC module is essentially identical to that observed for the DNA-interactive CCCC modules of the GATA-1 and steroid hormone receptor DNA binding domains, raising the possibility that the LIM motif may have a DNA binding function.


RO 15-4513 induces seizures in DBA/2 mice undergoing alcohol withdrawal.
RO 15-4513, an imidazodiazepine that has been reported to reverse some of the behavioral effects of ethanol, was given to DBA/2 mice. Although no animals treated with a 6 mg/kg dose of this drug had seizures, 20% of animals given 20 mg/kg of this drug had tonic seizures. Ethanol withdrawal was induced in DBA/2 mice treated with 4-methyl pyrazole using an inhalation paradigm. Mice were more likely to have a seizure during ethanol withdrawal if treated with RO 15-4513 (6 mg/kg) than if they received the vehicle. These data suggest administering RO 15-4513 as an alcohol antagonist to alcoholic subjects may increase the incidence of seizures.


The distribution of Francisella-like bacteria associated with coastal waters in Norway.
We report the diversity and distribution of Francisella species in Norwegian coastal and fresh waters following a nationwide survey in which water and sediment samples were collected from locations spanning almost the entire Norwegian coastline. In total, samples were obtained from 149 and 64 seawater and freshwater sites, respectively. DNA extracts from these environmental samples were initially screened by polymerase chain reaction (PCR) using Francisella genus-specific 16S rDNA primers. Positive samples were then amplified with genus-specific primers targeting Francisella succinate dehydrogenase A gene and Francisella philomiragia group-specific sequences for the SAICAR synthetase/phosphoribosylamine-glycine ligase gene. Francisella-related bacteria were identified in approximately 30% of seawater sampled sites, mainly in southern Norway, although a single positive sample was identified in the far north of the country. No PCR positives were identified from the freshwater sources. Sequences related to recognised species, both pathogenic and environmental, were identified, with the majority closely associated with F. philomiragia. However, a number of identified sequences probably represent previously undescribed species. Our data provide evidence of a significant background of Francisella spp. in geographical areas associated with outbreaks of fish francisellosis in Norway.


Transient Colonic Intussusception Versus Colon Adenocarcinoma: A Case Report on Ultrasound Features in the Emergency Department.
Intussusception in adults is a rare pathology due to the telescoping of a bowel segment into a section adjacent to it. Almost all cases are linked to a pathological lead point, which is often a colorectal carcinoma where the intussusception involves the large intestine. Likely to occur in the same clinical setting, the differential diagnosis between intussusception and colon carcinoma by ultrasound in the emergency department can be quite challenging. We present a rare case of transient colonic intussusception with a well-differentiated colon adenocarcinoma as the lead point in a 43-year-old patient. The point of care ultrasound (POCUS) revealed the target sign characteristic of intussusception at the level of maximum pain, associated with a pseudokidney sign. However, the pseudokidney sign was indeed an adenocarcinoma of the ascending colon visualized by colonoscopy and per op.


Temperature profile and residual heat of monopolar laparoscopic and endoscopic dissection instruments.
Endoscopic and laparoscopic electrosurgical devices (ED) are of great importance in modern medicine but can cause adverse events such as tissue injuries and burns from residual heat. While laparoscopic tools are well investigated, detailed insights about the temperature profile of endoscopic knives are lacking. Our aim is to investigate the temperature and the residual heat of laparoscopic and endoscopic monopolar instruments to increase the safety in handling ED. An infrared camera was used to measure the temperature of laparoscopic and endoscopic instruments during energy application and to determine the cooling time to below 50 °C at a porcine stomach. Different power levels and cutting intervals were studied to investigate their impact on the temperature profile. During activation, the laparoscopic hook exceeded 120 °C regularly for an up to 10 mm shaft length. With regards to endoknives, only the Dual Tip Knife showed a shaft temperature of above 50 °C. The residual heat of the laparoscopic hook remained above 50 °C for at least 15 s after activation. Endoknives cooled to below 50 °C in 4 s. A higher power level and longer cutting duration significantly increased the shaft temperature and prolonged the cooling time (p < 0.001). Residual heat and maximum temperature during energy application depend strongly on the chosen effect and cutting duration. To avoid potential injuries, the user should not touch any tissue with the laparoscopic hook for at least 15 s and with the endoknives for at least 4 s after energy application. As the shaft also heats up to over 120 °C, the user should be careful to avoid tissue contact during activation with the shaft. These results should be strongly considered for safety reasons when handling monopolar ED.


A cytosolic cytochrome b5-like protein in yeast cell accelerating the electron transfer from NADPH to cytochrome c catalyzed by Old Yellow Enzyme.
A 410-nm absorbing species which enhanced the reduction rate of cytochrome c by Old Yellow Enzyme (OYE) with NADPH was found in Saccharomyces cerevisiae. It was solubilized together with OYE by the treatment of yeast cells with 10% ethyl acetate. The purified species showed visible absorption spectra in both oxidized and reduced forms, which were the same as those of the yeast microsomal cytochrome b5. At least 14 amino acid residues of the N-terminal region coincided with those of yeast microsomal b5, but the protein had a lower molecular weight determined to be 12,600 by SDS-PAGE and 9775 by mass spectrometry. The cytochrome b5-like protein enhanced the reduction rate of cytochrome c by OYE, and a plot of the reduction rates against its concentration showed a sigmoidal curve with an inflexion point at 6x10(-8) M of the protein.


Ordering Characteristics Predictive of Noncontrast CT Head Positivity in the Emergency Department.
Recent decades have seen a steady increase in noncontrast head CT utilization in the emergency department with a concurrent rise in the practice of physician assistants (PAs) and nurse practitioners (NPs). The goal of this study was to identify ordering and patient characteristics predictive of positive noncontrast head CTs in the ED. We hypothesized NP/PAs would have lower positivity rates compared to physicians, suggestive of relative overutilization. We retrospectively identified ED patients who underwent noncontrast head CTs at a single institution: a nonlevel 1 trauma center, during a 7-year period, recording examination positivity, ordering provider training/experience, and multiple additional ordering/patient attributes. Exam positivity was defined as any intracranial abnormality necessitating a change in acute management, such as acute hemorrhage, hydrocephalus, herniation, or worsening prior findings. 6624 patients met inclusion criteria. 4.6% (280/6107) of physician exams were positive while 3.7% (19/517) of NP/PA exams were positive; however, differences were not significant. Increasing provider experience was not associated with positivity. Attributes with increased positivity were patient age (p < 0.001), daytime exam (p < 0.05), and indications regarding malignancy (p < 0.001) or focal neurologic deficit (p = 0.001). Attributes with decreased positivity were indications of trauma (p < 0.001) or vertigo/dizziness (p < 0.05). We found no significant difference in rates of exam positivity between physicians and NP/PAs, even accounting for years of experience. This suggests increasing utilization of head CTs in the ED is not due to the increasing presence of NP/PAs, and may be reflective of general practice trends and clear diagnostic algorithms leading to head CT.


Nuclear export regulation of COP1 by 14-3-3σ in response to DNA damage.
Mammalian constitutive photomorphogenic 1 (COP1) is a p53 E3 ubiquitin ligase involved in regulating p53 protein level. In plants, the dynamic cytoplasm/nucleus distribution of COP1 is important for its function in terms of catalyzing the degradation of target proteins. In mammalian cells, the biological consequence of cytoplasmic distribution of COP1 is not well characterized. Here, we show that DNA damage leads to the redistribution of COP1 to the cytoplasm and that 14-3-3σ, a p53 target gene product, controls COP1 subcellular localization. Investigation of the underlying mechanism suggests that COP1 S387 phosphorylation is required for COP1 to bind 14-3-3σ. Significantly, upon DNA damage, 14-3-3σ binds to phosphorylated COP1 at S387, resulting in COP1's accumulation in the cytoplasm. Cytoplasmic COP1 localization leads to its enhanced ubiquitination. We also show that N-terminal 14-3-3σ interacts with COP1 and promotes COP1 nuclear export through its NES sequence. Further, we show that COP1 is important in causing p53 nuclear exclusion. Finally, we demonstrate that 14-3-3σ targets COP1 for nuclear export, thereby preventing COP1-mediated p53 nuclear export. Together, these results define a novel, detailed mechanism for the subcellular localization and regulation of COP1 after DNA damage and provide a mechanistic explanation for the notion that 14-3-3σ's impact on the inhibition of p53 E3 ligases is an important step for p53 stabilization after DNA damage.


Metabolic risk-evaluation and prevention of recurrence in stone disease: does it make sense?
In this review, aspects on the importance of information on urine composition and selection of the most appropriate regimen for prevention of recurrence are discussed. For patients with urolithiasis the treatment is facilitated by urine analysis with estimates of supersaturation levels. Despite lack of strong scientific evidence for the benefit of selective versus non-selective prevention of recurrence in patients with calcium stone disease, there is currently both convincing and logical information in support of tailored/selective treatment regimens aiming at correction of abnormal target variables. Such an approach is also recommended in the EAU and AUA guidelines. It is important, however, that every preventive regimen is balanced between the effects on urine composition and patients' tolerance to the treatment in order to achieve satisfactory compliance. It is possible that future improved understanding of the causes of calcium stone formation might provide a different therapeutic approach.


Changes in cytosolic CA2+ are not involved in DDT-induced loss of gap junctional communication in WB-F344 cells.
Recent studies have demonstrated that the insecticide DDT is a tumor promoting agent. Similar to many other tumor promoting agents, DDT has been shown to inhibit gap junctional intercellular communication (GJIC) between cells in culture, and it has been suggested that DDT-induced loss of communication between adjacent cells may depend on changes in cytosolic free Ca2+ concentration [( Ca2+]i). In the present study, the role of [Ca2+]i in DDT-induced loss of GJIC was investigated in WB-F344 in rat liver cells using the scrape-loading/dye transfer assay (SLDT) and the Ca2+ fluorescent indicator, fura-2. Our results show that DDT at noncytotoxic concentrations caused a reversible loss of GJIC. Inhibition of GJIC was not associated with detectable increases in [Ca2+]i, and was not prevented by loading cells with the intracellular Ca2+ chelator, BAPTA. In addition, the hydroquinone, tBuBHQ, which caused a 2-3 fold sustained increase in [Ca2+]i, did not inhibit GJIC. Conversely, when untreated cells were loaded with increasing BAPTA concentrations, GJIC were lost. These results indicate that increases in [Ca2+]i are not responsible for DDT-induced loss of communication and that, in general, an increase in [Ca2+]i within physiological levels is not sufficient to abolish GJIC. However, Ca2(+)-dependent processes that are active at normal resting [Ca2+]i appear to be required for the maintenance of GJIC.


Epidemiology and significance of Q fever in the Federal Republic of Germany.
In the Federal Republic of Germany no large Q fever epidemics (more than 200 cases) have been encountered within the last 20 years; however, Q fever was prevalent throughout that period on a constant level (between 27 and 100 officially reported cases per year). Besides classical pneumonic Q fever, chronic forms associated with endocarditis, myocarditis and hepatitis were recently diagnosed for the first time in the Federal Republic of Germany. The disease Q fever in humans is often misdiagnosed as common cold or influenza, and more attention should be paid to this entity by the medical profession. Within ten years there has been a sharp increase of Q fever infections in livestock and pets as proved by seroepidemiologic investigations. Preliminary results of a seroepidemiological study indicate a parallel increase of seropositives in the human population, but further investigations on larger numbers of sera are required for statistic confirmation. There are reasons to believe that, in contrast to general opinion, in the Federal Republic of Germany C. burnetii is involved now in infertility in cattle, and besides being a zoonosis Q fever must be considered as a potentially important infectious disease of cattle causing economic losses in this country. Further investigations on this matter are required.


Comparison of in vivo kinematics of total knee arthroplasty between cruciate retaining and cruciate substituting insert.
The decision to choose cruciate retaining (CR) insert or cruciate substituting (CS) insert during total knee arthroplasty (TKA) remains a controversial issue. We hypothesized that there are different knee kinematics between CR and CS inserts and that a raised anterior lip design would offer a potential minimization of the paradoxical movement and provide joint stability. The objective of this study was to evaluate and compare kinematics of a CR and CS TKA of the same single-radius design. We investigated the in vivo knee kinematics of 20 knees with a CR TKA (10 knees in the CR insert and 10 knees in the CS insert). Patients were examined during deep knee flexion using fluoroscopy and femorotibial motion was determined using a 2- to 3-dimensional registration technique, which used computer-assisted design models to reproduce the spatial positions of the femoral and tibial components. We evaluated the knee range of motion (ROM), femoral axial rotation relative to the tibial component, anteroposterior translation, and kinematic pathway of the nearest point of the medial and lateral femoral condyles on the tibial tray. The average ROM was 121.0 ± 17.3° in CR and 110.8 ± 12.4° in CS. The amount of femoral axial rotation was 7.2 ± 3.9° in CR, and 7.4 ± 2.7° in CS. No significant difference was observed in the amount of anterior translation between CR and CS. The CR and CS inserts had a similar kinematic pattern up to 100° flexion that was central pivot up to 70° flexion and then paradoxical anterior femoral movement until 100° flexion. The present study demonstrated that there was no significant difference between the inserts in knee kinematics. These kinematic results suggested that the increased anterior lip could not control anterior movement in the CS insert.


Synanthropy of Sarcophagidae (Diptera) in southeastern Brazil.
Sarcophagidae (Diptera) are potential vectors of several pathogens. They are also very important in forensic entomology, providing basic information on the circumstances of death. The objective of this study was to determine the synanthropic index of adult Sarcophagidae collected in Rio Claro, state of São Paulo, southeastern Brazil. Sampling occurred between September 2009 and August 2010. Traps baited with sardines, beef liver, or minced meat were set for five consecutive days per month in three distinct ecological areas representing urban, rural, and forest environments. A total of 440 specimens of sarcophagids were collected. The most abundant species was Peckia (Sarcodexia) lambens (Wiedemann), followed by Oxysarcodexia thornax (Walker), Peckia (Euboettcheria) collusor (Curran & Walley), Peckia (Euboettcheria) sp., and Peckia (Pattonella) intermutans (Walker). The only species with positive synanthropic index values were O. thornax and P. (S.) lambens, which demonstrated a greater preference for inhabited areas. Peckia (Euboettcheria) florencioi (Prado & Fonseca), P. (P.) intermutans, and Peckia (Euboettcheria) australis (Townsend) were only found in the forested area, which demonstrates their importance in forensic entomology because of their preference for a particular type of environment. The greatest number of sarcophagids was found in the forest environment; however, only the forest and rural areas were significantly different in Sarcophagidae abundance.


Congenital atrophic dermatofibrosarcoma protuberans detected by COL1A1-PDGFB rearrangement.
Atrophic variant of dermatofibrosarcoma protuberans (DFSP) is a distinct form of DFSP. Here, we report the case of a 19-year-old woman with a small congenital atrophic plaque on the right precordium. The lesion remained atrophic for more than 10 years. Several years earlier, a portion of the plaque became tuberous and enlarged. Physical examination revealed a 25 × 30 mm erythematous atrophic plaque surrounded by three hard, smooth, and orange-colored nodules of varying sizes on the right precordium, along with visible subcutaneous adipose tissue and cutaneous veins. Biopsy of the nodule and atrophic plaque revealed dense proliferation of spindle-shaped tumor cells from the dermis to the subcutaneous adipose tissue, and positive immunostaining for CD34 and vimentin in addition to negative staining for factor XIIIa and α-smooth muscle actin. Reverse transcription polymerase chain reaction (RT-PCR) of the tumor tissue revealed the presence of a COL1A1-PDGFB fusion gene. Thus, congenital atrophic dermatofibrosarcoma protuberans was diagnosed. No metastasis to the lungs or regional lymph nodes was found on magnetic resonance imaging. Wide local excision and split-thickness skin grafting was performed and neither recurrence nor metastasis has been observed for 5 years and 8 months since the surgery. This case indicates that a congenital atrophic lesion could represent a quiescent phase of DFSP. Awareness of this rare condition can aid with early diagnosis and thereby improve the prognosis of DFSP.


Activities of thiamine-dependent enzymes in two experimental models of thiamine deficiency encephalopathy: 3. Transketolase.
Chronic thiamine deprivation in the rat leads to ataxia, loss of righting reflex and neuropathological damage to lateral vestibular nucleus. Before onset of neurological symptoms, transketolase (TK) activities were found to be selectively reduced by 25% in lateral vestibular nucleus and surrounding pons. Further progression of thiamine deprivation resulted in a generalized reduction in TK activity. Measurement of enzyme activity in the presence of added TPP cofactor in vitro did not lead to normalisation of enzyme activities suggesting loss of apoenzyme. Administration of thiamine to symptomatic thiamine-deprived rats resulted in reversal of neurological symptoms and to normalisation of defective TK activities in less vulnerable structures such as cerebral cortex, striatum and hippocampus; reduction of TK activity, however, persisted in brainstem and cerebellar regions. Pyrithiamine treatment results, within 3 weeks, in loss of righting reflex, convulsions and more widespread neuropathological damage compared to that observed following thiamine deprivation. TK activity was found to be significantly decreased before the onset of neurological symptoms in all brain regions and appearance of symptoms was accompanied by more severe reductions of TK. In contrast to chronic thiamine deprivation, TK activities following pyrithiamine treatment were: equally reduced in magnitude in vulnerable and non-vulnerable brain structures, unchanged following reversal of neurological abnormalities by thiamine administration.


Effect of maternal oxygen inhalation on foetal free radical activity: a prospective, randomized trial.
Maternal inhalation of 35-40% oxygen concentration has no significant effect on foetal partial pressure of oxygen, and 60-100% produced maternal and foetal hyperoxia with increased free radical activity. The benefit of 50% maternal oxygen inhalation on foetal oxygenation, oxidant stress and total antioxidant status (TAS) during Caesarean section (CS) has not been simultaneously evaluated. In this prospective, randomized, controlled trial 120 ASA physical status I-II, term pregnant women were recruited to elective CS (n = 60) and emergency CS (n = 60) and received either 50% oxygen or air inhalation following subarachnoid block (SAB). Patients and investigators were blinded to the inhaled oxygen concentration. The primary outcome of the study was foetal umbilical artery (UA) malondialdehyde (MDA) at birth. In both elective and emergency CS, there was no difference in foetal oxidative stress and TAS in spite of increase in maternal PaO2. In elective CS, maternal MDA was higher at delivery in mothers breathing 50% oxygen as compared to their own baseline values (P = 0.04). In emergency CS, maternal TAS at 10 min was lower in mothers inhaling 50% oxygen as compared to air (P = 0.01). The average duration of maternal oxygen supplementation was ~10.3 min in elective and ~7.4 min in emergency CS. Neonatal outcome, episodes of maternal hypotension and oxygen desaturation were similar in both the groups. Brief duration of 50% oxygen maternal inhalation during elective or emergency CS did not significantly affect foetal MDA and TAS under SAB.


Effect of cyclosporin A on the non-MHC endothelial antibody response in the rat.
The effect of cyclosporin A (CsA) on the in vivo humoral immune response against the non-MHC endothelial antigen that is present on the renal capillary and venous endothelium was tested in a rat model. Male MAXX rats were immunized using pooled spleen and lymph node cells from MHC-identical Brown Norway rats to induce the endothelial antibody response. The animals were treated with different doses of CsA for different periods and it was found that CsA suppressed the response completely and irreversibly when administered in a dose of 15 mg/kg/day with a minimum duration of therapy for 2 weeks. Animals that received a lower dose (10 mg/kg/day) or 15 mg/kg/day for 1 week, did show an initial response but failed to respond after repeated immunizations. The results show that CsA suppresses the humoral response to non-MHC alloantigens. Furthermore, a state of nonresponsiveness appears to be induced with doses which are not effective in suppressing the initial antibody response.


Clues from joint inversion of tsunami and geodetic data of the 2011 Tohoku-oki earthquake.
The 2011 Tohoku-oki (Mw 9.1) earthquake is so far the best-observed megathrust rupture, which allowed the collection of unprecedented offshore data. The joint inversion of tsunami waveforms (DART buoys, bottom pressure sensors, coastal wave gauges, and GPS-buoys) and static geodetic data (onshore GPS, seafloor displacements obtained by a GPS/acoustic combination technique), allows us to retrieve the slip distribution on a non-planar fault. We show that the inclusion of near-source data is necessary to image the details of slip pattern (maximum slip ~48 m, up to ~35 m close to the Japan trench), which generated the large and shallow seafloor coseismic deformations and the devastating inundation of the Japanese coast. We investigate the relation between the spatial distribution of previously inferred interseismic coupling and coseismic slip and we highlight the importance of seafloor geodetic measurements to constrain the interseismic coupling, which is one of the key-elements for long-term earthquake and tsunami hazard assessment.


Soft tissue pseudotumor following intramuscular injection of "DPT": a pitfall in magnetic resonance imaging.
We report the time-dependent magnetic resonance imaging (MRI) changes that resulted from an intramuscular injection of a commonly-used pediatric sedation regiment ("DPT"). These changes at the site of injection consist of a focal abnormality characterized by a slight increase in signal intensity on T1 weighted images and markedly increased signal intensity on T2 weighted images. Alterations in signal are detectable almost immediately after the injection and progress over the first 31 hours. This abnormality, which could be mistaken for real disease, persists up to 36 days following injection.


Periorbital necrotising fasciitis after minor trauma.
Necrotising fasciitis or streptococcal gangrene is a rare and often fatal soft tissue infection usually affecting the limbs and trunk. Facial involvement is exceedingly rare due to the excellent blood supply of this region. We report a case of initially misdiagnosed streptococcal gangrene of the eyelids precipitated by minor trauma and which progressed despite intensive medical therapy. A 53-year-old man with a history of alcohol abuse developed rapidly increasing left-sided periorbital oedema, erythema and skin vesicles soon after sustaining a laceration to his left upper lid. It was initially treated as herpes zoster ophthalmicus complicated by a secondary bacterial cellulitis. Bacterial cultures grew group A beta haemolytic Streptococcus pyogenes. Despite 8 days of high-dose parenteral antibiotic therapy and oral acyclovir, characteristic blisters formed and necrosis of the periorbital skin and subcutaneous tissues ensued. Surgical debridement was performed and the fasciitis rapidly resolved. Physicians and ophthalmologists must be aware of the risk factors, although rare, for periorbital necrotising fasciitis and the cardinal signs that differentiate this condition from common non-necrotising preseptal cellulitis. Prompt recognition and early surgical debridement are crucial in limiting the morbidity and mortality from severe forms of this disease.


Glucagon stimulation of mitochondrial respiration.
Acute glucagon treatment of intact rats has been found to cause a stimulation of hepatic mitochondrial respiration as measured by monitoring oxygen uptake polarographically. Rates of State 3 respiration with several NAD-linked substrates and succinate were increased significantly after hormonal treatment and isolation of mitochondria. This stimulation cannot be ascribed to a partial uncoupling effect since State 4 respiration as measured by monitoring oxygen uptake polarographically. Rates of State 3 respiration with either slightly increased or unchanged. Furthermore, rates of uncoupled respiration with these substrates were also stimulated after hormonal treatment. On the other hand, respiratory rates (State 3, 4, and uncoupled) with ascorbate-N,N,N',N'-tetramethyl-p-phenylenediamine as substrate were unaffected by glucagon treatment. The hormonally stimulated rates of respiration produced a corresponding increase in the rate of generation of high energy state as indicated in measurements of Ca2+ uptake by isolated mitochondria. Rates of Ca2+ uptake were monitored by two methods: measurement of initial rates of proton ejection following CaCl2 additions and measurement of disappearance of Ca2+ from the suspension medium using murexide as indicator in a dual wavelength spectrophotometer. A significant stimulation in the initial rate of succinate-dependent Ca2+ uptake was noted after glucagon treatment of animals and isolation of hepatic mitochondria. No effect of the hormonal treatment was seen on the extent of Ca2+ uptake or the stoichiometry of H+ ejected per Ca2+ taken up. That the hormonal effect on Ca2+ transport is at the level of the substrate-induced generation of high energy state is indicated by the observation that no effect of glucagon treatment is seen on ATP-dependent Ca2+ uptake. Glucagon-induced changes in the activities of substrate-metabolizing enzymes are considered unlikely for the following reasons: (a) previously published data showed a lack of a hormonal effect on pyruvate-metabolizing enzymes and (b) data in this study showing no effect of glucagon treatment on the activity of NAD-malate dehydrogenase as measured in mitochondrial lysates. All of these observations are consistent with either an activation of mitochondrial substrate transport and/or a stimulation of mitochondrial electron transport by glucagon treatment. Regardless of the exact mechanism involved, the effect of the hormonal treatment is to produce an increase in ATP synthetic and ion-pumping capability during a period of increased energy demand, i.e. increased gluconeogenesis.


Exacerbation of idiopathic paroxysmal kinesigenic dyskinesia in remission state caused by secondary hypoparathyroidism with hypocalcemia after thyroidectomy: evidence for ion channelopathy.
Most reported cases of paroxysmal kinesigenic dyskinesia (PKD) are idiopathic or familial; however, hypoparathyroidism is another unusual cause of secondary PKD. The pathomechanism of PKD remains poorly understood, and the association between idiopathic and secondary PKD remains an enigma, and has yet to be clearly elucidated. We recently encountered a patient with idiopathic PKD whose symptoms were aggravated by secondary hypoparathyroidism with hypocalcemia after having undergone a thyroidectomy. The patient's paroxysms were ameliorated by the normalization of serum calcium levels. The results discussed herein may provide support for the hypothesis that PKD is associated with neuronal ion regulation.


An efficient technique for the numerical solution of the bidomain equations.
Computing the numerical solution of the bidomain equations is widely accepted to be a significant computational challenge. In this study we extend a previously published semi-implicit numerical scheme with good stability properties that has been used to solve the bidomain equations (Whiteley, J.P. IEEE Trans. Biomed. Eng. 53:2139-2147, 2006). A new, efficient numerical scheme is developed which utilizes the observation that the only component of the ionic current that must be calculated on a fine spatial mesh and updated frequently is the fast sodium current. Other components of the ionic current may be calculated on a coarser mesh and updated less frequently, and then interpolated onto the finer mesh. Use of this technique to calculate the transmembrane potential and extracellular potential induces very little error in the solution. For the simulations presented in this study an increase in computational efficiency of over two orders of magnitude over standard numerical techniques is obtained.


Reward-related learning via multiple memory systems.
The application of a neuroeconomic approach to the study of reward-related processes has provided significant insights in our understanding of human learning and decision making. Much of this research has focused primarily on the contributions of the corticostriatal circuitry, involved in trial-and-error reward learning. As a result, less consideration has been allotted to the potential influence of different neural mechanisms such as the hippocampus or to more common ways in human society in which information is acquired and utilized to reach a decision, such as through explicit instruction rather than trial-and-error learning. This review examines the individual contributions of multiple learning and memory neural systems and their interactions during human decision making in both normal and neuropsychiatric populations. Specifically, the anatomical and functional connectivity across multiple memory systems are highlighted to suggest that probing the role of the hippocampus and its interactions with the corticostriatal circuitry via the application of model-based neuroeconomic approaches may provide novel insights into neuropsychiatric populations that suffer from damage to one of these structures and as a consequence have deficits in learning, memory, or decision making.


Two promoters of different strengths control the transcription of the mouse alpha-amylase gene Amy-1a in the parotid gland and the liver.
We show that two promoters of different strengths are involved in the tissue-specific expression of the alpha-amylase gene Amy-1a in the parotid gland and the liver of mouse. The weaker of the two promoters directs the synthesis of mRNA with a liver-type leader sequence. This promoter is active in both tissues. A promoter that is about 30-fold stronger is exclusively active in the parotid, where it directs the synthesis of an mRNA with a parotid-specific leader sequence. Neither the parotid nor the liver promoter is used in tissues that do not contain cytoplasmic alpha-amylase mRNAs, such as brain, kidney, and spleen. Nuclear transcripts that are initiated several kilobases upstream of the parotid cap site are detected in several tissues. They are most abundant in brain, and are apparently not processed into alpha-amylase mRNA.


Comparison of echocardiographic pulmonary flow Doppler markers in patients with massive or submassive acute pulmonary embolism and control group: A cross-sectional study.
Computed tomography angiography (CTA) is the gold standard for the diagnosis of massive (MPE) and submassive pulmonary embolism (SMPE). Ultrasound has not been accepted as a diagnostic tool. We aim to evaluate the pattern of pulmonary Doppler echocardiography in patients with pulmonary embolism (PE). From 2020 to 2022, 30 patients with acute MPE or SMPE confirmed by CTA and normal pulmonary pressures were selected. A control group was created with 30 individuals without PE. All patients had an echocardiography Doppler study of the pulmonary flow with a focus on early systolic notching (ESN), McConnell's (MC) sign, Right ventricular outflow tract velocity time integral (RVOT VTI), segmental thickness variability (STV), right ventricular end-diastolic diameter (RVEDD), tricuspid regurgitation (TR) gradient, pulmonary artery pressure (PAP), and acceleration (AT) or ejection time (ET). ESN was identified in 96.6% of PE patients and 0% of the control group (p < 0.001). In comparison with the control group, STV (p < 0.001), RVOT VTI (p < 0.001), ET (p = 0.04), and AT (p < 0.001) values were lower in patients with PE while RVEDD, TR gradient, PAP, ESN, MC sign, and d-shape were higher (p < 0.001). Identification of the ESN pattern and AT/ET < 0.4 showed excellent predictive ability for MPE and SMPE with a sensitivity of 97.0% and 100%, specificity of 99.0% and 97%, and an area under the ROC curve of 0.967 (95% CI 0.914-1.00) and 0.933 (95% CI 0.844-1.00), respectively. Doppler echocardiography with particular attention to ESN, may be a suitable noninvasive method for the diagnosis of MPE and SMPE. Further studies with more sample sizes are needed to confirm its diagnostic benefit.


Solitary true cyst of the pancreas.
We report a case of a woman diagnosed with a solitary true cyst of the pancreas. CT and especially MRI guided us in the diagnosis of this benign lesion. The cyst has been surgically removed because of secondary bile-duct obstruction causing painless jaundice. Clinical history, laboratory, imaging, and histological findings are reported.


Expressive flexibility and anxiety.
The ability to flexibly enhance and suppress emotional expressions plays an important role in emotion regulation and the fostering of social connections. Deficits in expressive flexibility have been linked with posttraumatic stress disorder and prolonged grief reactions. Previous studies have suggested that the ability to respond flexibly in the context of an immediate threat (a nonconscious prime) may be important. In this study we sought to extend this work by examining the impact of individual differences in anxiety on expressive flexibility. Eighty four participants with high and low trait anxiety viewed blocks of negative images with instructions to enhance or suppress emotional expressions. Across blocks one of three nonconscious primes (threat, safety, neutral) appeared before each image. Observers blind to the study's design rated participants' emotional expressiveness. Repeated Measures Anova's showed that high trait anxiety was associated with lower levels in enhancement ability. Further, low trait anxiety was associated with less emotion in response to the threat prime irrespective of expressive instruction. This study was cross-sectional which precludes causal relationships. Participants were drawn from a student population and the generalizability to other populations will need to be established CONCLUSIONS: This study identified trait anxiety as factor that may contribute to expressive flexibility deficits. High trait anxiety is a feature of many clinical conditions. Strategies to target expressive flexibility may relevant to a range of anxiety related clinical conditions.


Distinct functions of AKT isoforms in breast cancer: a comprehensive review.
AKT, also known as protein kinase B, is a key element of the PI3K/AKT signaling pathway. Moreover, AKT regulates the hallmarks of cancer, e.g. tumor growth, survival and invasiveness of tumor cells. After AKT was discovered in the early 1990s, further studies revealed that there are three different AKT isoforms, namely AKT1, AKT2 and AKT3. Despite their high similarity of 80%, the distinct AKT isoforms exert non-redundant, partly even opposing effects under physiological and pathological conditions. Breast cancer as the most common cancer entity in women, frequently shows alterations of the PI3K/AKT signaling. A plethora of studies addressed the impact of AKT isoforms on tumor growth, metastasis and angiogenesis of breast cancer as well as on therapy response and overall survival in patients. Therefore, this review aimed to give a comprehensive overview about the isoform-specific effects of AKT in breast cancer and to summarize known downstream and upstream mechanisms. Taking account of conflicting findings among the studies, the majority of the studies reported a tumor initiating role of AKT1, whereas AKT2 is mainly responsible for tumor progression and metastasis. In detail, AKT1 increases cell proliferation through cell cycle proteins like p21, p27 and cyclin D1 and impairs apoptosis e.g. via p53. On the downside AKT1 decreases migration of breast cancer cells, for instance by regulating TSC2, palladin and EMT-proteins. However, AKT2 promotes migration and invasion most notably through regulation of β-integrins, EMT-proteins and F-actin. Whilst AKT3 is associated with a negative ER-status, findings about the role of AKT3 in regulation of the key properties of breast cancer are sparse. Accordingly, AKT1 is mutated and AKT2 is amplified in some cases of breast cancer and AKT isoforms are associated with overall survival and therapy response in an isoform-specific manner. Although there are several discussed hypotheses how isoform specificity is achieved, the mechanisms behind the isoform-specific effects remain mostly unrevealed. As a consequence, further effort is necessary to achieve deeper insights into an isoform-specific AKT signaling in breast cancer and the mechanism behind it.


Molecular cloning, immunohistochemical localization, characterization and expression analysis of caspase-9 from the purse red common carp (Cyprinus carpio) exposed to cadmium.
Caspase-9, the essential initiator caspase is believed to play a central role in mitochondria-mediated apoptosis signaling. In this study, we isolated the caspase-9 gene from common carp, one of the most important industrial aquatic animals in China using rapid amplification of cDNA ends (RACE). The deduced amino acid sequence of caspase-9, composed of 436 amino acids, showed approximately 47.6% identity and 64.7% similarity to human caspase-9. It also possessed a conserved caspase-associated recruitment domain (CARD), a large subunit and a small subunit. Phylogenetic analysis clearly demonstrated that caspase-9 formed a clade with cyprinid fish caspase-9. Real-time quantitative PCR analysis revealed that caspase-9 transcripts were not significantly increased in kidney after exposure to cadmium (Cd). Whereas caspase-9 cleaved fragments were detected using Western blot analysis with the same Cd treatment condition. Furthermore, the result of immunohistochemical detection showed immunoreactivities were predominantly limited to the cytoplasm of renal tubular epithelial cells and no remarkable changes of immunopositive staining were observed after Cd treatment. Accordingly, the results signify that caspase-9 may play an essential role in Cd induced apoptosis.


Effectiveness of bilayer porous polyethylene membrane for alveolar ridge preservation: A randomized controlled trial.
Porous polyethylene has been successfully used in several medical applications with good outcomes. Based on this, a new bilayer porous polyethylene membrane (B-PPM) was developed for possibly being used as a membrane in alveolar ridge preservation. To evaluate the clinical efficacy of a new B-PPM in comparison to high-density polytetrafluoroethylene membrane (d-PTFE) in alveolar ridge preservation. Thirty patients were randomized into two groups according to the membranes used to cover the socket (B-PPM or d-PTFE). Wound healing was monitored at day 1, 3, 7, 14, 28, and 4 months postoperatively. Dimensional changes of alveolar ridge were measured immediately after tooth extraction and at 4 months later using intraoral scanner and cone beam computed tomography. Bone cores were harvested before implant placement. Implant stability at insertion and prior to prosthesis delivery were also measured. No significant difference in socket wound closure between groups was observed excepting at day 14 that B-PPM showed a faster wound closure than d-PTFE (P = .03). Greater bone resorptions were seen on buccal than lingual side and on coronal than apical part of the alveolar ridge. No significant difference in dimensional changes of alveolar ridge, new bone formation, connective tissue content, residual bone grafts, and implant stability between two groups. B-PPPM was safe and effective for alveolar ridge preservation.


LC-MS/MS Method for Measurement of Thiopurine Nucleotides (TN) in Erythrocytes and Association of TN Concentrations With TPMT Enzyme Activity.
Monitoring concentrations of thiopurine metabolites is used clinically to prevent adverse effects in patients on thiopurine drug therapy. We developed a LC-MS/MS method for the quantification of 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP) in red blood cells (RBCs). This method utilizes an automated cell washer for RBC separation from whole blood samples and washing of the separated RBCs. The lower limit of quantification of the method was 0.2 μmol/L for 6-TG (∼50 pmol/8 × 108 RBC) and 4 μmol/L for 6-MMP (∼1,000 pmol/8 × 108 RBC). The total imprecision of the assay was <3.0%. The upper limit of linearity for 6-TG and 6-MMP was 7.5 μmol/L and 150 μmol/L, respectively. The stability of the thiopurine metabolites under pre- and post-analytically relevant conditions was also evaluated. A good agreement was observed between this method and validated LC-MS/MS methods from three laboratories, except for ∼40% low bias for 6-MMP observed in one of the methods. The assessment of the association between 6-TG and 6-MMP concentrations with thiopurine S-methyltransferase (TPMT) phenotype and genotype demonstrated a statistically significant difference in the thiopurine metabolite concentrations between the TPMT groups with normal and intermediate activity of 6-MMP (p < 0.0001), while the difference in 6-TG concentrations was statistically not significant (p = 0.096). Among the samples with normal TPMT activity, higher concentrations of 6-MMP (p = 0.015) were observed in pediatric samples than in the samples of adults. No statistically significant differences were observed in the distributions of 6-TG and 6-MMP concentrations among the evaluated genotypes.


Efficacy and Safety of Limertinib (ASK120067) in Patients With Locally Advanced or Metastatic EGFR Thr790Met-Mutated NSCLC: A Multicenter, Single-Arm, Phase 2b Study.
Limertinib (ASK120067) is a newly developed third-generation EGFR tyrosine kinase inhibitor targeting both sensitizing EGFR and EGFR Thr790Met (T790M) mutations. This study aimed to evaluate the efficacy and safety of limertinib in patients with locally advanced or metastatic EGFR T790M-mutated NSCLC. This is a single-arm, open-label, phase 2b study conducted at 62 hospitals across the People's Republic of China. Patients with locally advanced or metastatic NSCLC with centrally confirmed EGFR T790M mutations in tumor tissue or blood plasma who progressed after first- or second-generation EGFR tyrosine kinase inhibitors or with primary EGFR T790M mutations were enrolled. Patients received limertinib 160 mg orally twice daily until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) assessed by independent review committee per the Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included disease control rate, progression-free survival (PFS), duration of response (DoR), overall survival, and safety. Safety was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. From July 16, 2019, to March 10, 2021, a total of 301 patients were enrolled and started the treatment of limertinib. All patients entered the full analysis set and safety set. By the data cutoff date on September 9, 2021, 76 (25.2%) remained on treatment. The median follow-up time was 10.4 months (range: 0.3-26.3). On the basis of full analysis set, the independent review committee-assessed ORR was 68.8% (95% confidence interval [CI]: 63.2%-74.0%) and disease control rate was 92.4% (95% CI: 88.8%-95.1%). The median PFS was 11.0 months (95% CI: 9.7-12.4), median DoR was 11.1 months (95% CI: 9.6-13.8), and median OS was not reached (95% CI 19.7 months-not evaluable). Objective responses were achieved across all prespecified subgroups. For 99 patients (32.9%) with central nervous system (CNS) metastases, the ORR was 64.6% (95% CI: 54.4%-74.0%), median PFS was 9.7 months (95% CI: 5.9-11.6), and median DoR was 9.6 months (95% CI: 8.1-15.2). For 41 patients who had assessable CNS lesion, the confirmed CNS-ORR was 56.1% (95% CI: 39.7%-71.5%) and median CNS-PFS was 10.6 months (95% CI: 5.6-not evaluable). In safety set, 289 patients (96.0%) experienced at least one treatment-related adverse event (TRAE), with the most common being diarrhea (81.7%), anemia (32.6%), rash (29.9%), and anorexia (28.2%). Grade ≥3 TRAEs occurred in 104 patients (34.6%), with the most common including diarrhea (13.0%), hypokalemia (4.3%), anemia (4.0%), and rash (3.3%). TRAEs leading to dose interruption and dose discontinuation occurred in 24.6% and 2% of patients, respectively. No TRAE leading to death occurred. Limertinib (ASK120067) was found to have promising efficacy and an acceptable safety profile for the treatment of patients with locally advanced or metastatic EGFR T790M-mutated NSCLC. NCT03502850.


[Clinical and radiological study of hypertrophic stenosis of the pylorus with early onset: case contribution (author's transl)].
Two cases of hypertrophic stenosis of the pylorus with symptomatology present at birth are reported and discussed. The cases were diagnosed radiologically and successfully operated.


Tissue fat quantification by magnetic resonance imaging: proton density fat fraction in polycystic ovary syndrome.
What are the potential differences between lean women with and without polycystic ovary syndrome (PCOS) in fat content in liver, vertebrae, paraspinal muscles, pancreas, subcutaneous (SCAT) and visceral adipose tissue (VAT)? Magnetic resonance imaging proton density fat fraction (PDFF) was used to establish these differences. This is a novel, non-invasive, operator-independent method with comparable diagnostic sensitivity and specificity to histologic examination for fatty liver disease, and strong correlation with muscle strength in neuromuscular studies. Twenty lean women with PCOS (mean age 23.9 ± 2.3; body mass index [BMI] 22.4 ± 2.0) and 20 age- and BMI-matched healthy women (mean age 24.9 ± 1.5; BMI 21.5 ± 1.9) were enrolled in this cross-sectional study. Anthropometric, biochemical and hormonal evaluations along with magnetic resonance imaging proton density fat fraction were carried out. PDFF% measurements of liver, SCAT and VAT were higher in the PCOS group, indicating increased fat content in these areas in lean women with PCOS compared with controls (P = 0.045, 0.030 and 0.037, respectively). In contrast, PDFF% values of vertebrae and paraspinal muscles in the PCOS group were lower than controls (P = 0.038 and 0.05, respectively). Pancreatic PDFF% measurements were similar between the groups. In the PCOS group, PDFF% of VAT was positively correlated with free androgen index (r = 0.69, P = 0.002). PDFF% measurement, an MRI-based novel biomarker, reveals increased fat in liver, SCAT and VAT, and decreased fat in vertebral bones and paraspinal muscles of lean women with PCOS.


Measurement of valgus and varus deformity in the lower limb.
A method is proposed for measuring deformities of the femur and tibia in the frontal plane. This forms part of a complex system of clinical and radiographic evaluation, suitable for the planning or surgical operations.


Ethanol effect on the ionic transfer through isolated human amnion. II. Cellular targets of the in vitro acute ethanol action and of the antagonism between magnesium, taurine and ethanol.
The ultrastructure of the human amniotic membrane from normal pregnancies at term, was studied by transmission electron microscopy. The results were analysed by a stereological method which indicates the ratio between the area of intercellular spaces (R1), microvilli (R2) and podocytes (R3) versus the cell area. Addition of ethanol (0.4 g/l) in the external medium decreased R1 and R3 and had no significant effect on R2. Ethanol reduced intercellular space and podocyte exchange surface. Two mM MgCl2 or 2 mM taurine restored R1 and R3 to normal values. The cellular targets of the antagonism between Mg, taurine and ethanol are particularly intercellular spaces and podocytes.


Thermoelectricity of interacting particles: a numerical approach.
A method for computing the thermopower in interacting systems is proposed. This approach, which relies on Monte Carlo simulations, is illustrated first for a diatomic chain of hard-point elastically colliding particles and then in the case of a one-dimensional gas with (screened) Coulomb interparticle interaction. Numerical simulations up to N>10^{4} particles confirm the general theoretical arguments for momentum-conserving systems and show that the thermoelectric figure of merit increases linearly with the system size.


Nonlinearity in eigenvalue-perturbation curves of simulated population projection matrices.
Sensitivity and elasticity analyses of population projection matrices (PPMs) are established tools in the analysis of structured populations, but they make a linear approximation of the usually nonlinear relationship between population growth and matrix elements. The evaluation of alternative population management interventions may be particularly vulnerable to error if the degree of nonlinearity depends on the element of the PPM that is targeted. The second self-derivative and the self-sensitivity of elasticity can be used to estimate the degree and sign of nonlinearity in sensitivity and elasticity analyses, respectively. Using simulated matrices, we demonstrate that the magnitude and sign of the second self-derivative and the self-sensitivity of elasticity vary systematically, according to the element of the PPM subject to perturbation. Population management prescriptions based on sensitivity and elasticity analysis should always be backed up by nonlinear analyses.


Cell wall glycosidase activities and protein content variations during fruit development and ripening in three texture contrasted tomato cultivars.
Excessive softening is the main factor limiting fruit shelf life and storage. It is generally acceptable now that softening of fruit which occurs during the ripening is due to synergistic actions of several enzymes on cell wall polysaccharides. As a subject for this study, we have assayed some glycosidase activities using three tomato species (Lycopersicon esculentum) contrasted for their texture phenotypes; the cherry tomato line Cervil (Solanum lycopersicum var. cerasiforme), a common taste tomato line Levovil (S. lycopersicum Mill.) and VilB a modern line, large, firmer and with good storage capability. Four glycosidase activities namely α-galactosidase, β-galactosidase, β-mannosidase and β-glucosidase were extracted from tomato's cell wall of the three species. Cell wall protein from fruits pericarp was extracted and compared among the three cultivars at the following stages; 14 days post anthesis (14DPA) fruit; 21 days post anthesis (21DPA), turning (breaker), red and over ripe. When glycolytic activities were also compared among these cultivars at the precited development stages, gross variations were noticed from stage to stage and also from species to species in accordance with the fruit firmness status. Interestingly, VilB cultivar, the firmer among the other two, though possessed the highest total protein content, exhibited the lowest enzymatic activities. Taken together, these results may therefore allow us to conclude that studies of glycolytic activities in a single tomato cultivar cannot be generalized to all species. On the other hand, relating fruit development to glycosidase activities should logically be coupled to these enzymes from cell wall compartment.


Sediment microbial fuel cell prefers to degrade organic chemicals with higher polarity.
By operating a SMFC in heavily contaminated sediment and analyzing its global organic chemical degradation profile, this study showed a brief trend that SMFC prefers to stimulate the degradation of organic chemicals with higher polarity. As a comparison, adding nitrate as a microbial respiration-based sediment remediation strategy preferred lower polarity chemicals. Both SMFC and nitrate reactors showed high degradation capacity in benzene homologs. These results provide crucial information for the selective and proper application of SMFC in bioremediation.


Rhizosphere microbiome: Functional compensatory assembly for plant fitness.
Environmental pressure to reduce our reliance on agrochemicals and the necessity to increase crop production in a sustainable way have made the rhizosphere microbiome an untapped resource for combating challenges to agricultural sustainability. In recent years, substantial efforts to characterize the structural and functional diversity of rhizosphere microbiomes of the model plant Arabidopsis thaliana and various crops have demonstrated their importance for plant fitness. However, the plant benefiting mechanisms of the rhizosphere microbiome as a whole community rather than as an individual rhizobacterium have only been revealed in recent years. The underlying principle dominating the assembly of the rhizosphere microbiome remains to be elucidated, and we are still struggling to harness the rhizosphere microbiome for agricultural sustainability. In this review, we summarize the recent progress of the driving factors shaping the rhizosphere microbiome and provide community-level mechanistic insights into the benefits that the rhizosphere microbiome has for plant fitness. We then propose the functional compensatory principle underlying rhizosphere microbiome assembly. Finally, we suggest future research efforts to explore the rhizosphere microbiome for agricultural sustainability.


Learning non-stationary conditional probability distributions.
While sophisticated neural networks and graphical models have been developed for predicting conditional probabilities in a non-stationary environment, major improvements in the training schemes are still required to make these approaches practically viable.


Advanced nanotherapies to promote neuroregeneration in the injured newborn brain.
Neonatal brain injury affects thousands of babies each year and may lead to long-term and permanent physical and neurological problems. Currently, therapeutic hypothermia is standard clinical care for term newborns with moderate to severe neonatal encephalopathy. Nevertheless, it is not completely protective, and additional strategies to restore and promote regeneration are urgently needed. One way to ensure recovery following injury to the immature brain is to augment endogenous regenerative pathways. However, novel strategies such as stem cell therapy, gene therapies and nanotechnology have not been adequately explored in this unique age group. In this perspective review, we describe current efforts that promote neuroprotection and potential targets that are unique to the developing brain, which can be leveraged to facilitate neuroregeneration.


Use of a non-ICU specialty ward for immediate post-operative management of head and neck free flaps; a randomized controlled trial.
Compare length of stay, flap failure rate, medical and surgical complications and cost when patients undergoing head and neck free flap reconstruction are monitored in an intensive care unit (ICU) versus a specialty ward unit postoperatively. A prospective, non-inferiority, randomized controlled trial was conducted from 7/22/2016 to 9/12/2018 at a single institution. Patients were randomized to the ICU or specialty ward unit. Flap check protocols were identical between the groups. Perioperative and postoperative outcome variables were assessed and compared. 131 patients were enrolled in the study and 118 ultimately underwent head and neck free flap reconstruction. 57 were randomized to the ICU and 61 to the specialty ward unit. There were no significant differences between the ICU and specialty ward unit groups with regard to demographic variables including age, gender, co-morbidities, tobacco or alcohol use, prior chemotherapy or radiation therapy treatment. There were no significant differences in perioperative variables including need for transfusion, tracheostomy, ischemia time, blood loss, fluid administration or post-operative antibiotic use. There was no significant difference in the primary outcome variable, length of stay. There were no significant differences in the number of the medical or surgical complications, flap failure rate, or hospital costs. In this prospective, randomized controlled trial, head and neck free-flap patients cared for on a specialty ward in the immediate post-operative period had equivalent outcomes to those cared for in the ICU.


Airway anomalies in patients with 22q11.2 deletion syndrome: A scoping review.
People with 22q11.2 deletion syndrome (22q11DS) can present with a wide variety of findings. Various airway anomalies have been described intermittently within this syndrome, but this feature has not been extensively investigated. Increased provider awareness of these findings may help guide clinical decision-making and improve overall patient outcomes. The objectives of this review are to identify the types of airway anomalies in 22q11DS and the prevalence of airway anomalies within symptomatic individuals. PubMed/MEDLINE, Cochrane Library, and EMBASE databases were searched in February 2022 for all available articles. Search terms included those that described 22q11DS or one of its synonymous conditions AND those that described airway anatomy and anomalies. The term airway anomaly was defined as any structural aberration in the conductive airway from the oral or nasal vestibule region to the mainstem bronchus. Studies were screened by two authors. A review of references was conducted. Eligible manuscripts underwent full-text review for quality appraisal and data extraction. From a total of 909 unique manuscripts, 58 studies were selected, describing 328 people. The prevalence of airway anomaly diagnosis within symptomatic individuals ranged from 14% to 74%. Twenty-two unique airway anomalies were described. Laryngeal web was the most frequently described anomaly, followed by airway malacia and subglottic stenosis. Laryngeal web was 40% sensitive for suggesting a diagnosis of 22q11DS. Among affected individuals, as many as 46% had multiple concomitant airway anomalies. Aside from respiratory symptoms, other features that prompted airway evaluation included difficult intubation or failed extubation. The findings within this review support the notion that a wide variety of airway anomalies may be seen in people with 22q11DS and that these findings have been discovered frequently in those with airway symptoms. Providers should maintain a low threshold to perform an airway examination in those with 22q11DS, especially when airway symptoms are present.


The characterisation and function of the polysaccharidases of human synovial fluid in rheumatoid and osteoarthritis.
A potential enzymic mechanism for the degradation of glycosaminogly cans was characterised using enzymes found in rheumatoid synovial fluid from the knee joint. This mechanism involves a true hyluronidase together with the concerted action of beta-glucuronidase and beta-N-acetylhexosaminidase. The contribution of the exopolysaccharidases to hyaluronate degradation was demonstrated by the use of specific inhibitors, while the distinct identity of a true hyaluronidase was shown by ammonium sulphate and agarose gel column fractionations. Only the hyluronidase fraction was capable of degrading high molecular weight hyaluronate. The exopolysaccharidase activities were shown to be markedly elevated in rheumatoid as compared to osteoarthritic synovial fluid and also normal serum. On the other hand, hyluronidase was similarly active in rheumatoid and osteoarthritic synovial fluids; both these levels were lower than that of normal human serum. Hyaluronidase in synovial fluid may thus be derived by diffusion from serum, since it is of relatively low molecular weight (60 000). The pH requirements of this enzyme system and the strong inhibition of hyaluronidase by synovial fluid make it unlikely that the mechanism operates extracellularly. It is proposed that as a lysosomal mechanism, however, it is an important contributing factor in the chronic erosion process characteristic of rheumatoid arthritis.


Persistent and emerging pollutants in the blood of German adults: Occurrence of dechloranes, polychlorinated naphthalenes, and siloxanes.
Human biomonitoring is a valid method to determine exposure, identify time trends, and monitor the effects of restrictions and measures. To characterize the recent exposure of Germans to persistent or emerging substances, we analyzed 4 dechloranes, 33 polychlorinated naphthalenes (PCNs), and 3 cyclic volatile methyl siloxanes (cVMS) in 42 plasma samples. The samples were collected from blood donors on a random selection. The median values of both Dechlorane Plus (DDC-CO) isomers were 1.23ng/gl.w. for anti- and 0.77ng/gl.w. for syn-DDC-CO. The two other dechloranes were found at lower levels. The median level of ∑-PCNs was 575pg/gl.w. (range: 101-1406pg/gl.w.). On average, the levels of PCNs in plasma were dominated by the congeners CN73, CN66/67, and CN51, which were responsible for approximately 71% of the total amount of PCNs. The cVMS octa-, deca-, and dodecamethylcyclotetrasiloxane could be determined in only some samples, with maximum values of 0.73, 0.48, and 0.79μg/l, respectively. Regarding dechloranes, our results are similar to those from other western countries but slightly lower than results from China. The levels of PCNs in German blood are similar to those observed in the U.S.A., but considerably lower than those reported for Korea. Using a preliminary TEF (toxic equivalency factor), the mean TEQ of the 9 quantifiable PCNs in Germany was low (0.36pg TEQ/gl.w.). The PCN levels in our study group are lower compared to previous studies.


Serum prolactin concentrations in patients infected with human immunodeficiency virus.
To analyze the prevalence, effects of HAART, and implications of hyperprolactinemia in HIV-infected patients. 192 HIV-infected men in stable clinical condition who underwent 355 measurements of prolactin were prospectively studied. Other clinical, immunologic, virologic, and laboratory parameters were also evaluated at the time of each prolactin measurement. Hyperprolactinemia was observed in 21.4% of the patients. Hyperprolactinemia was more commonly found in patients receiving opioids than in those who were not (p =.03), but it was not influenced by a past diagnosis of AIDS, presence of metabolic disturbances, gynecomastia, or viral load. Patients noninfected with hepatotropic viruses had slightly higher prolactin levels than those who were infected (p =.049). There were significant differences in the rates of hyperprolactinemia according to different CD4 strata, with higher rates in patients with higher CD4 counts. Similarly, hyperprolactinemic patients had higher CD4 counts than patients with normal prolactin (p =.038). Antiretroviral therapy was not associated with prolactin levels. Hyperprolactinemia is a common finding in HIV infection and is observed in about one fifth of male patients in stable clinical condition. It is not related to antiretroviral therapy, metabolic disturbances, liver disease, or viral load. The implications of its association with CD4 counts are unclear and should be investigated.


Gender-specific gene-environment interaction in alcohol dependence: the impact of daily life events and GABRA2.
Gender-moderated gene-environment interactions are rarely explored, raising concerns about inaccurate specification of etiological models and inferential errors. The current study examined the influence of gender, negative and positive daily life events, and GABRA2 genotype (SNP rs279871) on alcohol dependence, testing two- and three-way interactions between these variables using multi-level regression models fit to data from 2,281 White participants in the Collaborative Study on the Genetics of Alcoholism. Significant direct effects of variables of interest were identified, as well as gender-specific moderation of genetic risk on this SNP by social experiences. Higher levels of positive life events were protective for men with the high-risk genotype, but not among men with the low-risk genotype or women, regardless of genotype. Our findings support the disinhibition theory of alcohol dependence, suggesting that gender differences in social norms, constraints and opportunities, and behavioral undercontrol may explain men and women's distinct patterns of association.


[Kidney morphology in the hemolytic-uremic syndrome].
A case of hemolytic-uremic syndrome (Gasser syndrome) in a boy of 7 is described. The disease was accompanied by thrombocytopenia, anemia, hemorrhagic syndrome and acute renal insufficiency (ARI). Morphological lesions consisted in the predominant involvement of the kidneys presenting thrombosis of the glomerular capillaries and reglomerular arterioles, fine cortical necroses, and considerable degenerative changes in the tubular epithelium. The peculiar features of the disease included low intensity of hemolysis and the lack of the oligoanuric phase of ARI.


Safety and effectiveness of tofacitinib in Korean adult patients with rheumatoid arthritis: A post-marketing surveillance study.
The aim of this article is to assess the safety and effectiveness of tofacitinib in patients with rheumatoid arthritis in routine clinical settings in Korea. This is a prospective, multi-centre post-marketing surveillance study. Data were prospectively collected within 6 months after the start of tofacitinib therapy. Safety was evaluated based on the presence of adverse events (AEs) observed in patients who received at least one dose of tofacitinib. Effectiveness was assessed according to the proportion of patients who achieved low disease activity and remission, American College of Rheumatology 20 criteria (ACR20), European League Against Rheumatism (EULAR) response, and change of Disease Activity Score in 28 Joints (DAS28). The incidence rates [patients with events per 100 patient-years (PY)] of AEs and serious AEs were 56.92 and 10.69, respectively. Regarding AEs of special interest, the incidence rates were 4.33 per 100 PY for serious infections and infestations, 5.78 per 100 PY for herpes zoster, no event of tuberculosis, 0.29 per 100 PY for malignancy, 0.29 per 100 PY for venous thromboembolism (one event of deep vein thrombosis and no event of pulmonary embolism), 0.87 per 100 PY for major adverse cardiovascular event, and 0.58 per 100 PY for mortality. Moreover, ∼40.48% and 21.60% of patients achieved low disease activity and remission of DAS28-erythrocyte sedimentation rate. The EULAR response was classified as good responders with 39.12% in the DAS28-erythrocyte sedimentation rate. The benefit/risk profile of tofacitinib in adult patients with rheumatoid arthritis in routine clinical settings in Korea was similar to long-term clinical trial data.


Advances in multi-omics based quantitative microbial risk assessment in the dairy sector: A semi-systematic review.
With the increasing consumption of packaged and ready-to-eat food products, the risk of foodborne illness has drastically increased and so has the dire need for proper management. The conventional Microbial Risk Assessment (MRA) investigations require prior knowledge of process flow, exposure, and hazard assessment throughout the supply chain. These data are often generated using conventional microbiological approaches based either on shelf-life studies or specific spoilage organisms (SSOs), frequently overlooking crucial information such as antimicrobial resistance (AMR), biofilm formation, virulence factors and other physiological variations coupled with bio-chemical characteristics of food matrix. Additionally, the microbial risks in food are diverse and heterogenous, that might be an outcome of growth and activity of multiple microbial populations rather than a single species contamination. The uncertainty on the microbial source, time as well as point of entry into the food supply chain poses a constraint to the efficiency of preventive approaches and conventional MRA. In the last few decades, significant breakthroughs in molecular methods and continuously progressing bioinformatics tools have opened up a new horizon for risk analysis-based approaches in food safety. Real time polymerase chain reaction (qPCR) and kit-based assays provide better accuracy and precision with shorter processing time. Despite these improvements, the effect of complex food matrix on growth environment and recovery of pathogen is a persistent problem for risk assessors. The dairy industry is highly impacted by spoilage and pathogenic microorganisms. Therefore, this review discusses the evolution and recent advances in MRAmethodologies equipped with predictive interventions and "multi-omics" approach for robust MRA specifically targeting dairy products. It also highlights the limiting gap area and the opportunity for improvement in this field to ensure precision food safety.


Healthcare Professionals' Experiences of Assessing, Treating and Preventing Constipation Among Older Patients During Hospitalization: An Interview Study.
Constipation is a common and troublesome condition among older patients and can result in a variety of negative health consequences. It is often undiagnosed or undertreated. Healthcare professionals have a responsibility to understand and address patients' overall healthcare needs; so exploring their experiences is, therefore, highly relevant. The purpose of the study was to explore healthcare professionals' experiences of assessing, treating and preventing constipation among older patients. A qualitative design with an exploratory approach was used. The participants (registered nurses and physicians) were purposively sampled from three wards in a geriatric department in a medium-sized hospital in Sweden. Data were collected through focus group discussions and individual interviews, and analyzed using content analysis. Three categories were generated: Reasons for suboptimal management of constipation, Strategies for management, and Approaching the patients' needs. In the care of older patients at risk of or with constipation, decisions were made based on personal knowledge, personal experience and clinical reasoning. A person-centered approach was highlighted but was not always possible to incorporate. Different strategies for preventing and treating constipation were believed to be important, as was person-centered care, but were found to be challenging in the complexity of the care situation. It is important that healthcare professionals reflect on their own knowledge and clinical practice. There is a need for more support, information and specific guidance for healthcare professionals caring for older patients during hospitalization. Overall, this study underscores the importance of adequate access to resources and education in constipation management and that clinical guidelines, such as the Swedish Handbook for Healthcare, could be used as a guide for delivering high-quality care in hospitals.


Vasopressin increases 45Ca2+ influx in rat aortic smooth muscle cells.
[Arg8]Vasopressin (AVP)-induced 45Ca2+ influx was examined in vascular smooth muscle cells derived from rat aorta. AVP stimulated the 45Ca2+ influx in a concentration-dependent manner. The effect was abolished in the presence of La3+. The dihydropyridine calcium channel antagonist darodipine did not affect the AVP-induced influx of 45Ca2+. These data suggest that AVP stimulates in these cultured aortic smooth muscle cells a receptor-operated channel (ROC) that is permeable to Ca2+.


When Apologies become Meaningful: Perceptions of Apologies in Environmental Justice Communities.
In the United States, people of color from low income and working-class backgrounds are at disproportionate risk to pollution and other environmental stressors. These environmental justice communities (EJCs) can also experience increased risk when a natural disaster collides with a preexisting environmental risk. The current research is an exploratory field study that examines perceptions of environmental risk after a natural disaster and how meaningful a public apology would be in three communities. Residents (N=161) in two EJCs and a community without documented risks reported their environmental concerns and perceptions of public apologies. Overall, EJC residents reported greater concern about chemical hazard exposure than did residents with decreased risk. Furthermore, chemical exposure concerns facilitated public apology meaningfulness within the EJCs, but not in the decreased risk community.


Prenatal Polybrominated Diphenyl Ether Exposure and Body Mass Index in Children Up To 8 Years of Age.
Prenatal exposure to endocrine disruptors has been associated with increased risk of childhood obesity. However, epidemiologic studies on polybrominated diphenyl ethers (PBDEs) are limited despite animal studies indicating PBDEs' potential role as an obesogen. We investigated whether maternal concentrations of BDEs 28, 47, 99, 100, 153, and ΣPBDEs during pregnancy were associated with anthropometric measures in children aged 1-8 years. We examined 318 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study, a birth cohort enrolled from 2003 through 2006 (Cincinnati, OH). Serum PBDEs were measured at 16 ± 3 weeks gestation. We measured child height (1-8 years), weight (1-8 years), body mass index (BMI) (2-8 years), waist circumference (4-8 years), and body fat (8 years). To account for repeated measures, we used linear mixed models and generalized estimating equations to estimate associations between maternal PBDEs and child anthropometric measures. We found no statistically significant associations between prenatal PBDEs and height or weight z-score. A 10-fold increase in maternal serum BDE-153 was associated with lower BMI z-score (β = -0.36; 95% CI: -0.60, -0.13) at 2-8 years, smaller waist circumference (β = -1.81 cm; 95% CI: -3.13, -0.50) at 4-8 years, and lower percent body fat (β = -2.37%; 95% CI: -4.21, -0.53) at 8 years. A decrease in waist circumference at 4-8 years was observed with a 10-fold increase in BDE-100 (β = -1.50 cm; 95% CI: -2.93, -0.08) and ΣPBDEs (β = -1.57 cm; 95% CI: -3.11, -0.02). Reverse causality may have resulted in prenatal PBDEs, particularly BDE-153, and decreased BMI, waist circumference, and body fat. Citation: Vuong AM, Braun JM, Sjödin A, Webster GM, Yolton K, Lanphear BP, Chen A. 2016. Prenatal polybrominated diphenyl ether exposure and body mass index in children up to 8 years of age. Environ Health Perspect 124:1891-1897; http://dx.doi.org/10.1289/EHP139.


Mercury photoreduction and photooxidation kinetics in estuarine water: Effects of salinity and dissolved organic matter.
Net photoreduction of divalent mercury (Hg(II)) and volatilization of photoreduction products (i.e., elemental mercury (Hg(0))/dissolved gaseous mercury (DGM)) is a mechanism by which mercury burdens in ecosystems are lessened. The effects of salinity on mercury photoreactions were investigated while controlling the concentration of DOM (>1 kDa) using natural surface water from the tidal Jijuktu'kwejk (Cornwallis River) and processed with a tangential ultrafiltration-dilution technique. Pseudo first-order rate constants in estuarine water salinity dilutions ranged between 0.22 h-1 and 0.73 h-1. The amount of mercury available for photoreduction (Hg(II)RED) ranged between 67.2 and 265.9 pg. Pseudo first-order rate constants decreased with increasing salinity treatments (0-13.5 g L-1), with minimal change in rate constants occurring in higher salinity treatments (e.g. 20.3 or 26.8 g L-1), while Hg(II)RED increased with salinity. In lower salinity treatments, DOM was more photoactive. Taken together, results suggest changes in the mercury photoreduction mechanism from DOM-bound electron transfer to photochemically produced secondary reduction products with increasing salinity. Experiments examining photooxidation showed decreases in Hg (0) with longer exposure time, suggesting transformation of Hg(II)RED into a non-reducible form. This research highlights the importance of salinity and DOM interactions in estuarine surface water and their effects on mercury photochemistry.


Examining the UK Covid-19 mortality paradox: Pandemic preparedness, healthcare expenditure, and the nursing workforce.
To examine the UK pandemic preparedness in light of health expenditure, nursing workforce, and mortality rates in and relation to nursing leadership. The Global Health Security Index categorized the preparedness of 195 countries to face a biological threat on a variety of measures, producing an overall score. The United States of America and the United Kingdom were ranked 1st and 2nd most prepared in 2019. A cross-nation comparison of the top 36 countries ranked by Global Health Security Index score using a variety of online sources, including key data about each nation's expenditure on health and the nursing workforce, and compared these with mortality data for COVID-19. The extent of a country's pandemic preparedness, expenditure on healthcare and magnitude of the nursing workforce does not appear to impact mortality rates at this stage of the pandemic which is something of a paradox. It is important that arrangements for dealing with future global pandemics involve a range of agencies and experts in the field, including nurse leaders. To achieve the best outcomes for patients, nurse leaders should be involved in policy forums at all levels of government to ensure nurses can influence health policy.