Collaborative effects of electric field and fluid shear stress on fibroblast migration.
Cells are inherently exposed to a number of different biophysical stimuli such as electric fields, shear stress, and tensile or compressive stress from the extracellular environment in vivo. Each of these biophysical cues can work simultaneously or independently to regulate cellular functions and tissue integrity in both physiological and pathological conditions. Thus, it is vital to understand the interaction of multiple stimuli on cells by decoupling and coupling the stimuli in simple combinations and by investigating cellular behaviors in response to these cues. Here, we report a novel microfluidic platform to apply the combinatorial stimulation of an electric field and fluid shear stress by controlling two directional cues independently. An integrated microfluidic platform was developed using soft lithography to monitor the cellular migration in real-time in response to an electric field and fluid shear stress in single, simultaneous, and sequential modes. When each of these stimulations is applied separately, normal human dermal fibroblasts migrate toward the anode and in the direction of fluid flow in a dose-dependent manner. Simultaneous stimulation with an electric field and shear stress, which mimics a wound in vivo, enhances the directional migration of fibroblasts by increasing both directedness and trajectory speed, suggesting the plausible scenario of cooperation between two physical cues to promote wound healing. When an electric field and shear stress are applied sequentially, migration behavior is affected by the applied stimulation as well as pre-existing stimulating conditions. This microfluidic platform can be utilized to understand other microenvironments such as embryogenesis, angiogenesis and tumor metastasis.


Panton-Valentine leukocidin-positive Staphylococcus aureus in skin and soft tissue infections from primary care patients.
To characterize deep skin and soft tissue infections (dSSTI) caused by Panton-Valentine leukocidin (PVL)-positive versus PVL-negative Staphylococcus aureus isolates. We performed a retrospective analysis of patients' records including S. aureus isolates from outpatients with dSSTI. Samples had been submitted by primary care physicians, i.e. general practitioners, surgeons, dermatologists and paediatricians, located in Berlin, Germany, in 2007-2017. Bacterial isolates were identified and tested for antimicrobial susceptibility by VITEK 2; PVL was detected by PCR. In total, 1199 S. aureus isolates from 1074 patients with dSSTI were identified, and 613 (51.1%) of 1199 samples were PVL+. The median age of patients with PVL+S. aureus was lower than in patients with PVL- S. aureus (34 years, range 0-88 years, vs. 44 years, range 0-98 years; p < 0.0001). PVL was associated with repeated/multiple samples compared to single sample submission (69/92, 75% vs. 448/982, 45.6%, p < 0.0001; odds ratio (OR), 3.6; 95% confidence interval (CI), 2.2-5.8). Interestingly, the highest PVL positivity rate was found in isolates from gluteal (82/108, 75.9%; OR, 3.6; 95% CI, 2-5) or axillary (76/123, 61.8%; OR, 2; 95% CI, 1.1-3.3) localizations compared to isolates from the arm. The PVL positivity rate did not increase over time. Yet we noticed an increase in the trimethoprim/sulfamethoxazole (SXT) resistance rate in PVL+ isolates, mainly methicillin-sensitive S. aureus, when considering SXT resistance rates of 2007-2012 versus 2013-2017 (35/226, 15.5% vs. 74/289, 25.6%; p 0.01). In outpatients, gluteal and axillary dSSTI are indicative of PVL+S. aureus. Providing SXT as a complementary treatment for dSSTI should be based on susceptibility testing.


Assessment of muscular fatigue using vibromyography.
The purpose of this study was to investigate the behavior of electromyographical (EMG) and vibromyographical (VMG) signals in the time and frequency domains during a fatigue protocol. EMG and VMG records were obtained from the rectus femoris (RF) and vastus lateralis (VL) muscles of 11 adult male subjects during sustained, isometric knee extensor contractions performed at 70% of maximal voluntary contraction (MVC). The average median frequencies of the power density spectra decreased during the fatigue protocol for the EMG (from 73 to 54 Hz for RF, and from 75 to 57 Hz for VL) and the VMG signals (from 40 to 19 Hz for RF, and from 25 to 12 Hz for VL). Raw EMG signals remained the same qualitatively throughout the fatigue protocol, whereas corresponding VMG records appeared to become "smoother." The results of this study indicate that the pronounced decrease in the high-frequency content of the VMG signal may be observed in the time domain as a "smoothing" of the signal, and thus, that the raw VMG records (which may be displayed readily online) can be used to assess qualitatively the onset and progression of muscular fatigue.


[Where do we perform sleep test: In the laboratory or at home?]
Obstructive sleep apnea syndrome (OSAS) is an important public health problem seen in 14.3% of male, and 5% of female population which leads to higher morbidity, and mortality rates because of its outcomes effecting many organ systems including cardiovascular, and cerebrovascular systems. Despite its higher prevalence in community, sleep laboratories both in our country, and in the world remain incapable of diagnosing these patients, and 80-90% of the cases with OSAS can not be diagnosed. As an alternative to gold standard polysomnographic examinations this desperate condition revived the use of more practical, and less expensive portable monitorization devices which can be used at home without the need for help of a technician. In this article we will discuss whether application of sleep test on a patient with suspect OSAS in the laboratory or at home will be more appropriate regarding effectiveness, and reliability of the test in the light of the scientific data.


Implications and outcomes of cardiac grafts refused by pediatric centers but transplanted by adult centers.
According to Organ Procurement Transplant Network policy, hearts from donors age <18 years are offered to pediatric recipients before being offered to adults of the same health status. We aimed to analyze differences in the use of adolescent donor hearts between adult and pediatric candidates and also to analyze the outcomes of pediatric candidates in which an adolescent donor heart was refused and later used in an adult recipient. All adolescent donors (age 12-17 years) for 2000 to 2015 were identified using the standard United Network of Organ Sharing dataset and matched against the Potential Transplant Recipient dataset. Of the 2457 adults who received an adolescent heart, 855 (35%) received it after at least 1 refusal by a pediatric candidate (n = 844). Of the 844 pediatric candidates, 643 (76%) subsequently underwent transplantation (designated PCTs) and 201 (24%) never underwent transplantation (designated PCNTs). Among the latter group, 87 patients (43%) died or became too ill for transplantation. These 87 PCNTs refused 256 hearts that were later accepted by adult recipients. Donor quality was the most common reason for refusal. Overall, adult recipients had similar post-transplantation survival compared with PCTs, all pediatric transplants, and all adult transplants (P > .10). A breakdown of adolescent heart donors by year shows a trend toward increased use in pediatric candidates. A significant number of adolescent donor hearts that are refused by pediatric centers result in excellent post-transplantation outcomes in adult recipients. One in 10 pediatric candidates died on the waitlist after refusal of these hearts used by adult recipients. This warrants careful evaluation of the refusal criteria used by pediatric centers. Encouragingly, there now appears to be a trend toward an increased use of adolescent donor hearts by pediatric centers.


CT findings of rupture, impending rupture, and contained rupture of abdominal aortic aneurysms.
With the increasing use of cross-sectional imaging for a variety of medical and surgical conditions affecting the abdomen and pelvis, familiarity with the imaging features of aneurysm rupture--and the findings suspicious for impending or contained aneurysm rupture--is crucial for all radiologists. This pictorial essay will review the imaging findings of rupture of abdominal aortic aneurysms and of complicated aneurysms. Prompt detection of abdominal aortic aneurysm rupture or impending rupture is critical because emergent surgery may be required and patient survival may be at stake.


Sexual behavior risk factors associated with bacterial vaginosis and Chlamydia trachomatis infection.
Few studies have demonstrated that bacterial vaginosis (BV) is associated with sexual behavior risk factors similar to those for other sexually transmitted diseases. The objective of this study was to determine the prevalence of these factors in a multivariate analysis of data from women infected with BV and Chlamydia trachomatis, and noninfected control subjects. To study detailed sexual behavior risk factors reported by women with BV versus genital C. trachomatis infection (CT) and by non-BV-infected controls. A cross-sectional study was conducted with 1,011 women (Swedish Women's Health Study) recruited from family planning and youth clinics in Eskilstuna and Stockholm, Sweden (November, 1989-January, 1991). Participants were evaluated for the presence of BV, CT, Neisseria gonorrhoeae, Treponema pallidum, Trichomonas vaginalis, and human immunodeficiency virus, and interviewed in detail with respect to sexual behaviors. Statistical comparisons were made using chi-square test (Pearson and likelihood ratio), t test, and logistic regression multivariate analysis. Of 956 women eligible for analysis, the prevalence of BV and CT was 13.7% and 8.9%, respectively. The comparison group consisted of the remaining 825 women without BV. After excluding those with concomitant CT infection, there were 118 women with BV who were compared with 72 women with CT infection only. Sexual factors associated with BV versus the comparison group were a short-term relationship before and after sexual debut, high number of lifetime sexual partners, multiple partners during the last month, high orgasm ability, and more frequent history of group sex, sexual abuse, and rape. When the BV group was compared with the CT group, there were no significant differences in sexual activity risk factors, except for a higher frequency of experience of casual sex in the CT group. Bacterial vaginosis is associated with sexual behavior risk factors similar to those associated with genital CT infection.


Telehealth in Physical Medicine and Rehabilitation: A Narrative Review.
Telehealth refers to health care interactions that leverage telecommunication devices to provide medical care outside the traditional face-to-face, in-person medical encounter. Technology advances and research have expanded use of telehealth in health care delivery. Physical medicine and rehabilitation providers may use telehealth to deliver care to populations with neurologic and musculoskeletal conditions, commonly treated in both acute care and outpatient settings. Patients with impaired mobility and those living in locations with reduced access to care may particularly benefit. Video-teleconferencing has been shown to be effective for management of burn patients during acute rehabilitation, including reduced health care use expenses and less disruptions to care. Telehealth can facilitate developing interprofessional care plans. Patients with neurologic conditions including stroke, spinal cord injury, traumatic brain injury, and amyotrophic lateral sclerosis may use telehealth to monitor symptoms and response to treatment. Telehealth also may facilitate occupational and physical therapy programs as well as improve weight management and skin care in patients with chronic conditions. Other applications include imaging review in sports medicine, symptom management and counseling in concussion, traumatic brain injury, and pain management programs. Limitations of telehealth include barriers in establishing relationship between medical provider and patient, ability to perform limited physical examination, and differences in payment models and liability coverage. The expansion of telehealth services is expected to grow and has potential to improve patient satisfaction by delivering high quality and value of care.


Effect of spermine on mitochondrial glutathione release.
Spermine prevents glutathione release induced in rat liver mitochondria by the combined addition of Ca2+ and phosphate. Spermine also inhibits mitochondrial swelling, membrane potential decrease, oxygen uptake and [14C] sucrose entry stimulated by the above reported agent. Mitochondrial swelling is completely prevented by 25 microM spermine while higher concentrations (100 microM) are required for the full inhibition of glutathione release. Therefore, polyamines decrease the mitochondrial inner membrane permeability and, by preventing mitochondrial glutathione loss, also act as protective agents against oxidative stress.


Loewner driving functions for off-critical percolation clusters.
We numerically study the Loewner driving function Ut of a site percolation cluster boundary on the triangular lattice for p<pc . It is found that Ut shows a drifted random walk with a finite crossover time. Within this crossover time, the averaged driving function Ut shows a scaling behavior -(pc-p)t(nu+1)/2nu with a superdiffusive fluctuation whereas, beyond the crossover time, the driving function Ut undergoes a normal diffusion with Hurst exponent 1/2 but with the drift velocity proportional to (pc-p)nu , where nu=4/3 is the critical exponent for two-dimensional percolation correlation length. The crossover time diverges as (pc-p)-2nu as p-->pc.


The Melbourne Colorectal Cancer Study: reflections on a 30-year experience.
This article reflects on 30 years of conducting the Melbourne Colorectal Cancer Study, a comprehensive, population-based investigation of colorectal cancer (CRC). The study had an incidence arm, a case-control arm and a survival arm, and contributed considerable knowledge about CRC risk, aetiology, prevention and screening. The incidence arm: confirmed high rates of CRC in Australia and the prevalent view that rates rise in first-generation immigrants from countries with low rates of CRC; and enabled the first report of high rates of colon cancer among Australian Jewish people and the first report of high rectal cancer rates anywhere. The case-control arm elicited: the contribution of family history, antecedent colorectal polypectomy and multiple antecedent stressful life events to CRC risk; the risk of rectal cancer in habitual beer drinkers; the first dietary risk score (emphasising the importance of a diet pursued over adult life that is high in foods of plant origin and fish, and low in fat and red meat); and the highly protective effect of regular aspirin use (stimulating much research globally, with the possibility of aspirin becoming an important preventive agent). The survival arm: found an adjusted CRC-specific 5-year survival rate of 42% among patients with CRC and 85% among matched control subjects; confirmed cancer stage as the most important single determinant of survival; and found that the survival rate among people with the earliest stage of CRC was only marginally lower than that of matched community control subjects, underlining the importance of early detection.


Effect of cell density on hormonal secretion from human pituitary adenomas in vitro.
Cell density effects were investigated on tumorous hormonal secretion from 10 pituitary adenomas: 3 somatotrophinomas secreting GH and PRL; 7 gonadotrophinomas, 3 co-secreted both FSH and LH, all 7 secreted LH. Enzymatically dispersed tissue was plated out in 24-well plates at 5 x 10(5), 10(5), 5 x 10(4) and 10(4) cells/well in serum-free media. Media were collected weekly for 2 weeks. In 3 of 3 somatotrophinomas, GH and PRL secretion was higher (p < 0.05) at both week 1 and 2 from 10(4) cells/well, but similar at other cell densities. In all 3 gonadotrophinomas, the FSH secretory rate was highest at 5 x 10(5) cells/well which fell as cell density decreased. Conversely, in 7 of 7 gonadotrophinomas the LH secretory rate was highest at 10(4) cells/well (p < 0.01) which fell as cell density increased. These data suggest that paracrine factors may modulate tumorous GH, PRL, FSH and LH secretion, and show that FSH and LH secretion vary inversely as cell density increases.


Hypoxia inhibits the recombinant alpha 1C subunit of the human cardiac L-type Ca2+ channel.
1. Whole-cell patch clamp recordings were used to investigate the effects of hypoxia on recombinant human L-type Ca2+ channel alpha 1C subunits stably expressed in human embryonic kidney (HEK 293) cells. 2. Ca2+ channel currents were reversibly inhibited by hypoxia (PO2 < 90 mmHg). The degree of inhibition depended on the charge carrier used, Ca2+ currents being more O2 sensitive than Ba2+ currents. 3. Hypoxic inhibition of Ca2+ channel currents was more pronounced at lower activating membrane potentials (< or = +30 mV), and was associated with a slowing of activation kinetics. Current inactivation and deactivation were unaffected by hypoxia. 4. Since hypoxia similarly regulates native L-type Ca2+ channels in vascular smooth muscle cells, our results suggest that hypoxic regulation of L-type Ca2+ channels arises from modification of structural features of the alpha 1 subunit common to cardiac and smooth muscle L-type channels.


Chromosomal changes detected by fluorescence in situ hybridization in patients with acute lymphoblastic leukemia.
To investigate patients with acute lymphoblastic leukemia (ALL) for TEL/AML1 fusion, BCR/ABL fusion, MLL gene rearrangements, and numerical changes of chromosomes 4, 10, 17 and 21 by fluorescence in situ hybridization (FISH) and to determine the relationship and the significance of those findings. Fifty-one American patients (34 men and 17 women) were included in this study. Of them there were 41 patients with pro-B cell type ALL, 9 with B cell type ALL and 1 with T cell type ALL. Chromosome metaphases of each sample were prepared according to standard protocols. Fluorescence in situ hybridization was performed using commercially available DNA probes, including whole chromosome painting probes, locus specific probes, specific chromosome centromere probes and dual color/multiple color translocation fusion probes. The digital image analysis was carried out using Cytovision and Quips FISH programs. An overall incidence of chromosomal anomalies, including t (9;22), MLL gene rearrangements, t (12;21), and numerical chromosomal anomalies of chromosomes 4, 10, 17 and 21 was found in 33 patients (65%). Thirty-one of them were pediatric patients and two adults. The t (12;21) was the commonest chromosomal anomaly detected in this population; 14 out of the 45 pediatric patients (31%) were positive for TEL/AML1 fusion, among which three had an additional derivative 21 [t (12;21)], four had a deletion of 12p and two had an extra copy of chromosome 21. All 14 patients with positive TEL/AML1 fusion had ALL pre-B cell or B-cell lineage according to standard immunotyping. The percentage of cells with fusion signals ranged from 20% to 80%. All fourteen patients positive for TEL/AML1 gene fusion were mosaic. Three out of the 14 patients positive for the TEL/AML1 gene fusion were originally reported to be culture failures and none of the remaining eleven samples had been found to have chromosome 12 abnormalities by conventional cytogenetic techniques. All pediatric patients with pre-T or T cell lineage and the six adults were negative for TEL/AML1 fusion. One patient had double Philadelphia chromosomes, three had a rearrangement or a deletion of the MLL gene, one had t (4;11) and two had a deletion of the MLL. One of the patients with an MLL deletion also had a large ring of chromosome 21, and r (21) was caused by AML1 gene tandemly duplicated at least five times. The second case with the MLL deletion was also unique, the patient had a t (12;21) as well. A total of 20 patients had numerical changes (gain or loss) of chromosomes 4, 10, 17 and 21. Eight patients were found to have trisomies of three or four different chromosomes. Interestingly, seven of these patients did not have TEL/AML1, BCR/ABL or the MLL gene rearrangement; one did have the TEL/AML1 gene fusion. Eleven patients with pro-B cell or B cell type ALL (9 children with ALL, 2 adults with ALL) had numerical changes of chromosome 21 (gain 1 or 2 chromosome 21), among them, 10 patients had no structural alteration of chromosome 21, and one was combined by t (12; 21). Four patients had a monosomy of chromosome 17 and three out of these patients with monosomy 17 also had a fusion signal of TEL/AML1. FISH plays an important role in detecting chromosome changes, especially in some cryptic chromosome translocations and patients with culture failures. This study found a trend towards a division between patients who had structural changes such as t (12;21) or a ring chromosome 21 and those who had numerical changes of chromosome 21 as well as the patients with TEL/AML1 fusion and patients with the coexistence of numerical chromosomal changes of chromosomes 4, 10 and 17. In our opinion there are two separate mechanisms which lead to the development or progression of leukemia.


High-Intensity Exercise as a Dishabituating Stimulus Restores Counterregulatory Responses in Recurrently Hypoglycemic Rodents.
Hypoglycemia is a major adverse effect of insulin therapy for people with type 1 diabetes (T1D). Profound defects in the normal counterregulatory response to hypoglycemia explain the frequency of hypoglycemia occurrence in T1D. Defective counterregulation results to a large extent from prior exposure to hypoglycemia per se, leading to a condition called impaired awareness of hypoglycemia (IAH), the cause of which is unknown. In the current study, we investigate the hypothesis that IAH develops through a special type of adaptive memory referred to as habituation. To test this hypothesis, we used a novel intense stimulus (high-intensity exercise) to demonstrate two classic features of a habituated response, namely dishabituation and response recovery. We demonstrate that after recurrent hypoglycemia the introduction of a novel dishabituating stimulus (a single burst of high-intensity exercise) in male Sprague-Dawley rats restores the defective hypoglycemia counterregulatory response. In addition, the rats showed an enhanced response to the novel stimulus (response recovery). We make the further observation using proteomic analysis of hypothalamic extracts that high-intensity exercise in recurrently hypoglycemic rats increases levels of a number of proteins linked with brain-derived neurotrophic factor signaling. These findings may lead to novel therapeutic approaches for individuals with T1D and IAH.


Outcome of full-thickness chest wall resection for isolated breast cancer recurrence.
Local breast cancer recurrence is often viewed as an early sign of rapidly progressive metastatic disease for which chest wall resection (CWR) can provide no benefits. We retrospectively reviewed our experience with full-thickness CWR to determine whether long-term outcomes warranted this aggressive procedure. Between 2001 and 2012, 33 women (mean age, 50.7 years; range, 33-72 years) underwent en-bloc CWR with curative intent. Mean disease-free interval from initial tumour resection was 90.5 months (range, 2-252 months). Resection included skin, muscle and an average of 2.7 ribs (range, 1-8 ribs) and was extended to the sternum (n = 21), subclavian vessels (n = 9), lung (n = 8), pericardium (n = 8), phrenic nerve (n = 2) or T1 nerve root (n = 1). Complete R0 resection was achieved in 31 (94%) patients. Chest wall reconstruction was performed in 28 patients, with polytetrafluoroethylene mesh (n = 17) or titanium ribs (n = 11). A musculocutaneous flap was used in 17 (52%) patients. Postoperative morbidity was 36%, with no deaths. Median follow-up was 33 months (range, 3-96 months). Median survival was 69 months and 1-, 3- and 5-year survival rates were 100, 81 and 63%, respectively. Recurrence developed in 13 patients, including 12 with distant metastases. Disease-free survival rates were 77, 57 and 50% after 1, 3 and 5 years, respectively. By univariate analysis, only resection extended to intrathoracic structures was associated with better survival (P = 0.033). En-bloc full-thickness CWR eventually extended to adjacent structures provides acceptable morbidity and excellent long-term survival and should be considered the treatment of choice in locally recurrent breast cancer.


AST to platelet ratio index (APRI) for the noninvasive evaluation of liver fibrosis.
Liver biopsy is the recognized gold standard for liver fibrosis staging. The aspartate aminotransferase to platelet ratio index (APRI) has been proposed as a noninvasive and readily available tool for the assessment of liver fibrosis in chronic hepatitis C (CHC). This study aimed to validate, in a Mexican tertiary health care setting, the diagnostic usefulness of APRI in CHC, nonalcoholic fatty liver disease (NAFLD) and autoimmune hepatitis (AIH). In an observational, cross-sectional, comparative and retrolective fashion, consecutive patients with CHC, NAFLD or AIH were evaluated. Fibrosis was staged using the METAVIR scale. Receiver operating characteristic ROC curves were constructed for significant fibrosis, advanced fibrosis and cirrhosis. One-hundred-sixty-four CHC, 30 NAFLD and 42 AIH patients were evaluated. For the diagnosis of significant fibrosis, APRI values delimited an area under de ROC curve (AUC) of 0.776 in CHC, 0.564 in NAFLD, and 0.602 in AIH patients. For advanced fibrosis, the AUCs were 0.803, 0.568 and 0.532 in CHC, NAFLD and AIH patients, respectively. For cirrhosis, AUCs were 0.830 and 0.599 in CHC and AIH patients. In conclusion, APRI can be a useful noninvasive alternative for the diagnosis of significant fibrosis and cirrhosis in our CHC patients. APRI values of < or = 0.3 and < or = 0.5 rule out significant fibrosis and cirrhosis, and a value of > or = 1.5 rules in significant fibrosis. In patients with NAFLD, APRI values tend to increase with the degree of fibrosis, suggesting that it could be useful in this disease. APRI appears to be of no value in patients with AIH.


Application value of a computer-aided diagnosis and management system for the detection of lung nodules.
Computer-aided diagnosis (CAD) systems can help reduce radiologists' workload. This study assessed the value of a CAD system for the detection of lung nodules on chest computed tomography (CT) images. The study retrospectively analyzed the CT images of patients who underwent routine health checkups between August 2019 and November 2019 at 3 hospitals in China. All images were first assessed by 2 radiologists manually in a blinded manner, which was followed by assessment with the CAD system. The location and classification of the lung nodules were determined. The final diagnosis was made by a panel of experts, including 2 associate chief radiologists and 1 chief radiologist at the radiology department. The sensitivity for nodule detection and false-positive nodules per case were calculated. A total of 1,002 CT images were included in the study, and the process was completed for 999 images. The sensitivity of the CAD system and manual detection was 90.19% and 49.88% (P<0.001), respectively. Similar sensitivity was observed between manual detection and the CAD system in lung nodules >15 mm (P=0.08). The false-positive nodules per case for the CAD system were 0.30±0.84 and those for manual detection were 0.24±0.68 (P=0.12). The sensitivity of the CAD system was higher than that of the radiologists, but the increase in the false-positive rate was only slight. In addition to reducing the workload for medical professionals, a CAD system developed using a deep-learning model was highly effective and accurate in detecting lung nodules and did not demonstrate a meaningfully higher the false-positive rate.


Delayed thrombosis of the basilar artery after stenting for a basilar trunk dissection aneurysm. A case report and review of the literature.
A 30-year-old man was referred in our department for treatment of a midbasilar trunk aneurysm. His presenting symptoms included headache and dizziness. A CT scan at another hospital showed no significant findings whereas a digital subtraction angiogram disclosed a dissecting aneurysm in the midbasilar trunk, and there was severe stenosis in the basilar artery. After discussion, we planned to use stent-assisted-coil embolization technique. During the procedure, a LEO stent (Balt, Montmorency, France) was implanted into the basilar artery across the aneurysm neck, but fearing acute basilar artery occlusion because of stent collapse or thrombus we did not fill coils into the aneurysm. After the procedure, the completion angiography demonstrated considerably decreased flow into the aneurysm, with stasis persisting into the venous phase of angiography. The patient awoke from general anaesthesia after the procedure and had no additional neurological symptoms, he was discharged three days later and used clopidogrel and aspirin for antiplatelet therapy. Six months later when he was admitted for a recheck, a DSA showed the basilar artery was occluded completely and the aneurysm had disappeared even though the patient remained neurologically normal.


Phagocytosis in acute leukemia.
The phagocytic potential of leukemic cells in various types of acute leukemia was studied. Cases included lymphoblastic leukemia, myeloblastic leukemia, myelomonocytic leukemia, monocytic leukemia, progranulocytic leukemia, blast transformation of chronic myelocytic leukemia, and unclassified leukemias. Cytochemical stains were used as an aid in classification. These included Sudan black B, naphthol AS-D chloroacetate esterase, alpha-naphthyl butyrate esterase, acid phosphatase, and periodic acid-Schiff. Phagocytosis was evaluated after incubation of leukemic cells with Candida albicans. Rare phogocytic activity was seen in lymphoblastic leukemia, unclassified leukemias, blast crises in chronic myelocytic leukemia, and progranulocytic leukemia. Myeloblastic leukemias were feebly phagocytic. Myelomonocytic leukemia and monocytic leukemia both exhibited marked phagocytosis which distinguished them from the other acute leukemias. Myelomonocytic leukemia could be differentiated from acute monocytic leukemia by its greater phagocytic capacity.


Suicide mortality at time of armed conflict in Ukraine.
The purpose of this review is to explore the dynamics of suicide mortality rates in Ukraine during an ongoing armed conflict between 2014 and 2015. Suicide mortality data were obtained by reviewing annual analytical releases from the State Service for Emergent Situations of Ukraine and annual release of Russian Federal Service of State Statistics. Suicide mortality in mainland Ukraine and in the Crimea region demonstrated a mild decrease, whereas suicide mortality in the regions directly involved in the armed conflict demonstrated a prominent decrease. The results of this review support Durkheim theory. The limitation of this review includes general concern about quality of data at time of armed conflict in the country.


Regional Sub-Saharan Africa Total Diet Study in Benin, Cameroon, Mali and Nigeria Reveals the Presence of 164 Mycotoxins and Other Secondary Metabolites in Foods.
In the framework of the first multi-centre Sub-Saharan Africa Total Diet Study (SSA-TDS), 2328 commonly consumed foods were purchased, prepared as consumed and pooled into 194 composite samples of cereals, tubers, legumes, vegetables, nuts and seeds, dairy, oils, beverages and miscellaneous. Those core foods were tested for mycotoxins and other fungal, bacterial and plant secondary metabolites by liquid chromatography, coupled with tandem mass spectrometry. The highest aflatoxin concentrations were quantified in peanuts, peanut oil and maize. The mean concentration of the sum of aflatoxins AFB1, AFB2, AFG1 and AFG2 (AFtot) in peanut samples (56.4 µg/kg) exceeded EU (4 µg/kg) and Codex (15 µg/kg) standards. The AFtot concentration (max: 246.0 µg/kg) was associated with seasonal and geographic patterns and comprised, on average, 80% AFB1, the most potent aflatoxin. Although ochratoxin A concentrations rarely exceeded existing Codex standards, it was detected in unregulated foods. One palm oil composite sample contained 98 different metabolites, including 35.4 µg/kg of ochratoxin A. In total, 164 different metabolites were detected, with unspecific metabolites like asperglaucide, cyclo(L-pro-L-val), cyclo (L-pro-L-tyr), flavoglaucin, emodin and tryptophol occurring in more than 50% of composite samples. Aflatoxin B1 (AFB1), fumonisin B1 (FB1), sterigmatocystin (STC), ochratoxin A (OTA), citrinin (CIT) and many other secondary fungal metabolites are frequent co-contaminants in staple foods, such as maize and sorghum. Populations from North Cameroon and from Benin may, therefore, suffer chronic and simultaneous exposure to AFB1, FB1, STC, OTA and CIT, which are prevalent in their diet.


Characterization of protein kinase PsSRPKL, a novel pathogenicity factor in the wheat stripe rust fungus.
As in other eukaryotes, protein kinases (PKs) are generally evolutionarily conserved and play major regulatory roles in plant pathogenic fungi. Many PKs have been proven to be important for pathogenesis in model fungal plant pathogens, but little is currently known about their roles in the pathogenesis of cereal rust fungi, devastating pathogens in agriculture worldwide. Here, we report on an in planta highly induced PK gene PsSRPKL from the wheat stripe rust fungus Puccinia striiformis f. sp. tritici (Pst), one of the most important cereal rust fungi. PsSRPKL belongs to a group of PKs that are evolutionarily specific to cereal rust fungi. It shows a high level of intraspecies polymorphism in the kinase domains and directed green fluorescent protein chimers to plant nuclei. Overexpression of PsSRPKL in fission yeast induces aberrant cell morphology and a decreased resistance to environmental stresses. Most importantly, PsSRPKL is proven to be an important pathogenicity factor responsible for fungal growth and responses to environmental stresses, therefore contributing significantly to Pst virulence in wheat. We hypothesize that cereal rust fungi have developed specific PKs as pathogenicity factors for adaptation to their host species during evolution. Thus, our findings provide significant insights into pathogenicity and virulence evolution in cereal rust fungi.


The Time-dependent Changes in EMG Recorded from the Medial Gastrocnemius of Young and Elderly Amputees.
[Purpose] Dysfunction of lower extremity muscles is one risk factor of falls for amputee patients. However, the change in muscle activity pattern and balance ability of amputees who have no experience in standing with prosthesis during the period from prosthesis fitting to regaining the ability to walk has never been studied. Therefore, the objectives of the present study were to elucidate changes over time in the muscle activity pattern and walking speed from first prosthesis fitting to hospital discharge. We also investigated the differences of muscle activity during standing between younger and elderly amputee patients. [Methods] Electromyography measurements were performed on the gastrocnemius of the intact leg during standing. The test subjects were asked to shift their center of gravity forward. [Results] Two unique patterns of gastrocnemius activities were observed over time. In a younger patient, the amount of muscular activity of the gastrocnemius gradually increased over time. In an elderly patient, however, the amount of muscular activity of gastrocnemius gradually decreased over time. [Conclusion] The time-dependent changes in gastrocnemius muscle activities are indicative postural control ability. Therefore, understanding the time-dependent changes in muscle activities during rehabilitation and the differences of postural control between younger and elderly patients would contribute to the development of effective rehabilitation programs for each patient.


Influence of short-chain fatty acids on vascular tone.
Results from research on the influence of short-chain fatty acids (SCFA) (C3-C6) on vascular tone are reported. Isolated vascular smooth muscle strips were studied in vitro and the arterial blood pressure of guinea-pigs injected with SCFA was taken. On the basis of results from these first two methods, the level of PG F2 alpha was determined by radioimmunoassay. The experiments indicate that in vitro the SCFA have spasmogenic effects which are blocked by indomethacin and aspirin and which are reduced by the inhibitor of the activating effect of PG F2 alpha, PG E2, and PG I2-SC19220. The effects of SCFA on smooth muscle strips used as a bioassay are analogous to the effects of PG F2 alpha on the same tissue. The injection of butyric acid into guinea-pigs causes hypertension which is not manifest if indomethacin pretreatment is carried out. Radioimmunoassay results indicate that the level of PG F2 alpha in the blood of animals treated with butyric acid is significantly increased.


Croton ruizianus: platelet proaggregating activity of two new pregnane glycosides.
The MeOH extract of the aerial parts of Croton ruizianus afforded two new pregnane glycosides 1 and 2, together with the morphinandienone alkaloids flavinantine (3) and O-methylflavinantine (4). Their structures were elucidated by NMR experiments including 1H-1H (1D TOCSY and 2D DQF-COSY) and 1H-13C (HSQC, HMBC) spectroscopy. The proaggregating activity of the MeOH extract and the isolates were evaluated. Although the MeOH extract and pregnane glycosides (at different doses) were found to promote platelet aggregation, flavinantine (3) and O-methylflavinantine (4) showed only slight activity. The ability of the MeOH extract and the four compounds to act synergistically with thrombin was also evaluated. All the tested compounds were successful in augmenting the aggregating effect of thrombin, although to different degrees.


Tissue factor: a critical role in inflammation and cancer.
A series of coordinated enzymatic reactions takes place in the body whenever blood clots. The major physiological initiator of these reactions is a membrane-bound glycoprotein known as tissue factor (TF), which is normally separated from the bloodstream by the vascular endothelium. Bleeding, caused by injury or tissue damage, activates a complex enzyme cascade as TF becomes exposed to the bloodstream. In disease states, leukocytes or the vascular endothelium may abnormally express TF to cause intravascular coagulation. The blood-coagulation cascade is also relevant to diseases such as hemophilia, in which patients are deficient in blood proteins necessary for clotting, and is linked to vascular diseases such as heart attack and stroke, in which clotting can lead to the occlusion of blood vessels. Coagulation is also activated in inflammation and cancer. In this article, we discuss characteristics of TF and review its role in inflammation and cancer.


Latent murine leukemia virus infection characterized by the release of non-infectious virions.
Clonal cell lines derived from cultures infected with a polytropic MuLV release vastly different levels of infectious virions ranging from undetectable to very high. Low producing clones release an overwhelming proportion of non-infectious virions containing retroviral RNA but deficient in the Env protein. Non-infectious virion production is not due to an inability of the cells to support infectious MuLV production or to an inherent replicative defectiveness of the proviruses. Reinfection of the lowest producing lines with the polytropic or an ecotropic MuLV results in enormous increases in the specific infectivity of the released virions. This indicates a reversible state of retroviral latency characterized by the release of non-infectious virions that is likely the result of insufficient levels of Env protein required for infectivity. The latency state described here may have important roles in in vivo retroviral infections including alterations of the immune response and the production of defective interfering particles.


Relationships among caregiver factors and quality of life in care recipients with irreversible dementia.
Using Lawton's (1983) model of quality of life (QoL) in older adults as a guiding framework, the central purpose of this ongoing longitudinal, prospective study is to examine predictors of QoL outcomes in persons with irreversible dementia as they move through the disease stages. From an initial sample of 96 caregiver/care recipient pairs, 73 (N = 146) pairs remain at the 18-month data collection point. Changes in care recipient outcomes from baseline to the 18-month assessment include significant declines in mental status, productive behaviors, and functional ability, with a statistically significant improvement in depression. Controlling for 12-month mental ability, caregiver factors at 12 months predicting care recipient QoL outcomes at 18 months include psychologic well being predicted by the quality of the relationship with the caregiver and activity participation. Depression was predicted by activity participation as well. Care recipient functional ability was predicted by activity participation and caregiver role stress (disruption to routines and social functioning). Two of the three aspects of care recipient productive behaviors were predicted by caregiver factors, with quality of the relationship predicting problem solving and caregiver role stress (negative attitudes toward care recipient) and total social contacts predicting care recipient social behaviors in the expected direction. Lawton's QoL model was supported by this analysis, with a total explained variance of 32% for three (psychologic well being, productive behaviors, functional ability) of the five (physical impairment and perceived personal control not included) components of care recipient QoL outcomes.


A disposable voltammetric sensor for the determination of diphenylamine using modified pencil graphite electrode.
This study reports the electrochemical monitoring and sensing of diphenylamine (DPA), an anti-scald agent on a modified pencil graphite electrode (PGE). DPA is also a potentially toxic environmental pollutant. A polymer of tyrosine synthesized by electrochemical process was utilized for the determination of DPA in real samples. The electrodes were characterized using IR, SEM, EDAX, AFM and EIS analyses. As far as we know, this is first time reporting the utilization of modified PGE via green approach for the monitoring of DPA. A dynamic linear range of 1.00-117.11 µM with a lower detection limit (LOD) of 0.7050 µM was showed by this sensor for the electrochemical quantification of DPA. The electrochemical oxidation of DPA on the modified sensor followed a mixed adsorption -diffusion controlled kinetics. The sensor also showed good anti-interference property for the determination of DPA in real samples. Furthermore, the developed sensor was applied for the selective sensing of DPA from real apple extracts with good recovery. The real sample analysis was validated with standard spectrophotometric method.


Genome Sequence of Hypervirulent Aeromonas hydrophila Strain HZAUAH.
Aeromonas hydrophila, a zoonotic bacterium found in an expansive range of aquatic ecosystems, has been reported to cause severe diseases in fish, amphibians, reptiles, and mammals, including humans. Herein, we report the draft genome of the hypervirulent A. hydrophila strain HZAUAH isolated from a crucian in China.


Characterizing genetic and environmental influences on variable DNA methylation using monozygotic and dizygotic twins.
Variation in DNA methylation is being increasingly associated with health and disease outcomes. Although DNA methylation is hypothesized to be a mechanism by which both genetic and non-genetic factors can influence the regulation of gene expression, little is known about the extent to which DNA methylation at specific sites is influenced by heritable as well as environmental factors. We quantified DNA methylation in whole blood at age 18 in a birth cohort of 1,464 individuals comprising 426 monozygotic (MZ) and 306 same-sex dizygotic (DZ) twin pairs. Site-specific levels of DNA methylation were more strongly correlated across the genome between MZ than DZ twins. Structural equation models revealed that although the average contribution of additive genetic influences on DNA methylation across the genome was relatively low, it was notably elevated at the highly variable sites characterized by intermediate levels of DNAm that are most relevant for epigenetic epidemiology. Sites at which variable DNA methylation was most influenced by genetic factors were significantly enriched for DNA methylation quantitative trait loci (mQTL) effects, and overlapped with sites where inter-individual variation correlates across tissues. Finally, we show that DNA methylation at sites robustly associated with environmental exposures such as tobacco smoking and obesity is also influenced by additive genetic effects, highlighting the need to control for genetic background in analyses of exposure-associated DNA methylation differences. Estimates of the contribution of genetic and environmental influences to DNA methylation at all sites profiled in this study are available as a resource for the research community (http://www.epigenomicslab.com/online-data-resources).


A new model for the human alimentary tract: the work of a Committee 2 task group.
The absorbed doses received from ingested radionuclides are currently calculated using the method outlined in ICRP Publication 30. It has been recognised by the ICRP that some of the assumptions used to calculate absorbed doses should be reviewed. A new physiologically based model has been developed, applicable to intakes of radionuclides in food and liquids by children and adults. All parts of the alimentary tract are included, additional sites for absorption and retention are considered and the morphometric and transit parameter values are reviewed in coordination with the ICRP Reference Man revision. Features of the new model are explained and preliminary dose estimates are presented.


Nonmaturing Fistulae: Epidemiology, Possible Interventions, and Outcomes.
Autogenous arteriovenous fistulae are the best method for prolonged, successful dialysis access. However, a substantial limitation of dialysis fistulae is their high primary failure rate, estimated to be as high as 70% for radiocephalic fistulae. Fistula maturation is influenced by demographic risk factors as well as anatomical barriers, the latter of which can be readily identified by noninvasive ultrasound imaging and physical examination. These barriers can be categorized as inflow problems (native arterial disease, arteriovenous anastomotic stenosis, and juxta-anastomotic stenosis) or outflow problems (proximal venous stenosis or collateral veins). Venous stenoses represent the most commonly observed barrier to fistula maturation. By treating these barriers with a systematic approach, interventionalists can significantly improve the likelihood of a fistula's usability for dialysis.


Validation of the Brief Sense of Community Scale among youth of color from an underserved urban community.
Neighborhood sense of community (SOC) is a key construct in the community psychology literature. While the research on neighborhood SOC has progressed significantly, there is a need to further validate the Brief Sense of Community Scale (BSCS) among youth. A critical area of scholarship, therefore, is to examine the factor structure of the BSCS among a cohort of adolescents, particularly from the United States. This study tested the factor structure of the BSCS among a sample of urban youth of color (N = 383) using SPSS AMOS, a structural equation modeling software. After testing the factor structure, we examined the relationships between each of the BSCS subscales and conceptually related variables (e.g., psychological empowerment, relational power, and school importance). Results from this study confirm the first- and second-order factor structure of the BSCS among youth. BSCS and its underlying subscales were both correlated with one another and correlated with the intrapersonal component of psychological empowerment, relational power, and school importance. Our findings have critical implications for the field of community psychology and the development and use of the BSCS among adolescents.


Electroactive Smart Polymers for Biomedical Applications.
The flexibility in polymer properties has allowed the development of a broad range of materials with electroactivity, such as intrinsically conductive conjugated polymers, percolated conductive composites, and ionic conductive hydrogels. These smart electroactive polymers can be designed to respond rationally under an electric stimulus, triggering outstanding properties suitable for biomedical applications. This review presents a general overview of the potential applications of these electroactive smart polymers in the field of tissue engineering and biomaterials. In particular, details about the ability of these electroactive polymers to: (1) stimulate cells in the context of tissue engineering by providing electrical current; (2) mimic muscles by converting electric energy into mechanical energy through an electromechanical response; (3) deliver drugs by changing their internal configuration under an electrical stimulus; and (4) have antimicrobial behavior due to the conduction of electricity, are discussed.


The role of inflammation in diabetic kidney disease.
Diabetic kidney disease (DKD) has been the leading cause of chronic kidney disease for over 20 years. Yet, over these two decades, the clinical approach to this condition has not much improved beyond the administration of glucose-lowering agents, renin-angiotensin-aldosterone system blockers for blood pressure control, and lipid-lowering agents. The proportion of diabetic patients who develop DKD and progress to end-stage renal disease has remained nearly the same. This unmet need for DKD treatment is caused by the complex pathophysiology of DKD, and the difficulty of translating treatment from bench to bed, which further adds to the growing argument that DKD is not a homogeneous disease. To better capture the full spectrum of DKD in our design of treatment regimens, we need improved diagnostic tools that can better distinguish the subgroups within the condition. For instance, DKD is typically placed in the broad category of a non-inflammatory kidney disease. However, genome-wide transcriptome analysis studies consistently indicate the inflammatory signaling pathway activation in DKD. This review will utilize human data in discussing the potential for redefining the role of inflammation in DKD. We also comment on the therapeutic potential of targeted anti-inflammatory therapy for DKD.


Epigenetics for Plant Improvement: Current Knowledge and Modeling Avenues.
Epigenetic variations are involved in the control of plant developmental processes and participate in shaping phenotypic plasticity to the environment. Intense breeding has eroded genetic diversity, and epigenetic diversity now emerge as a new source of phenotypic variations to improve adaptation to changing environments and ensure the yield and quality of crops. Here, we review how the characterization of the stability and heritability of epigenetic variations is required to drive breeding strategies, which can be assisted by process-based models. We propose future directions to hasten the elucidation of complex epigenetic regulatory networks that should help crop modelers to take epigenetic modifications into account and assist breeding strategies for specific agronomical traits.


Role of a surfactant in caustic alkali cleaning of polyethylene terephthalate surfaces fouled with organic substances.
The role of polyoxyethylene lauryl ether (POELE), a nonionic surfactant, in removing bovine serum albumin (BSA) and catechin from polyethylene terephthalate (PET) particles was quantitatively studied. Relatively large fractions of adsorbed BSA and catechin were removed from PET particles under weak alkaline conditions below pH 9, whereas cleaning with high concentrations of NaOH was not so effective, especially on the removal of BSA. This was attributed to the lower susceptibility of PET particles to water-based alkali (OH-) cleaning because of the lower degree of the polarity of PET surfaces. The combined use of NaOH solutions of moderate pHs and POELE could successfully improve the efficiency of cleaning of PET particles without a significant dissolution of PET materials. There was a good correlation between the lowered surface tension (7) of the NaOH solution with POELE and the removal efficiency of BSA or catechin. No effect of POELE was observed on the NaOH cleaning of hydrophilic alumina (A12O3) particles fouled with BSA. It could be concluded that the role of POELE in NaOH cleaning of PET particles was to lower the gamma of the NaOH solution and hence to facilitate penetration of OH- ions into the PET-BSA and PET-catechin interfaces.


Association of close-range contact patterns with SARS-CoV-2: a household transmission study.
Households are an important location for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, especially during periods when travel and work was restricted to essential services. We aimed to assess the association of close-range contact patterns with SARS-CoV-2 transmission. We deployed proximity sensors for two weeks to measure face-to-face interactions between household members after SARS-CoV-2 was identified in the household, in South Africa, 2020-2021. We calculated the duration, frequency, and average duration of close-range proximity events with SARS-CoV-2 index cases. We assessed the association of contact parameters with SARS-CoV-2 transmission using mixed effects logistic regression accounting for index and household member characteristics. We included 340 individuals (88 SARS-CoV-2 index cases and 252 household members). On multivariable analysis, factors associated with SARS-CoV-2 acquisition were index cases with minimum Ct value <30 (aOR 16.8 95% CI 3.1-93.1) vs >35, and female contacts (aOR 2.5 95% CI 1.3-5.0). No contact parameters were associated with acquisition (aOR 1.0-1.1) for any of the duration, frequency, cumulative time in contact, or average duration parameters. We did not find an association between close-range proximity events and SARS-CoV-2 household transmission. Our findings may be due to study limitations, that droplet-mediated transmission during close-proximity contacts plays a smaller role than airborne transmission of SARS-CoV-2 in the household, or due to high contact rates in households. Wellcome Trust (Grant number 221003/Z/20/Z) in collaboration with the Foreign, Commonwealth, and Development Office, United Kingdom.


Superior vena cava obstruction post laparoscopic cholecystectomy: A case report.
Clinicians should have a high index of suspicion of superior vena cava obstruction in a patient presenting with painful lateral neck and ipsilateral chest swelling post laparoscopic procedures. High doses of Clexane can be used as a substitute for thrombolytic therapy where it is contraindicated.


Near-Infrared Spectroscopy: A Promising Prehospital Tool for Management of Traumatic Brain Injury.
Introduction Early identification of traumatic brain injury (TBI) is essential. Near-infrared spectroscopy (NIRS) can be used in prehospital settings for non-invasive monitoring and the diagnosis of patients who may require surgical intervention. The handheld NIRS Infrascanner (InfraScan Inc.; Philadelphia, Pennsylvania USA) uses eight symmetrical scan points to detect intracranial bleeding. A scanner was tested in a physician-staffed helicopter Emergency Medical Service (HEMS). The results were compared with those obtained using in-hospital computed tomography (CT) scans. Scan time, ease-of-use, and change in treatment were scored. A total of 25 patients were included. Complete scans were performed in 60% of patients. In 15 patients, the scan was abnormal, and in one patient, the scan resulted in a treatment change. Compared with the results of CT scanning, the Infrascanner obtained a sensitivity of 93.3% and a specificity of 78.6%. Most patients had severe TBI with indication for transport to a trauma center prior to scanning. In one patient, the scan resulted in a treatment change. Evaluation of patients with less severe TBI is needed to support the usefulness of the Infrascanner as a prehospital triage tool. Promising results were obtained using the InfraScan NIRS device in prehospital screening for intracranial hematomas in TBI patients. High sensitivity and good specificity were found. Further research is necessary to determine the beneficial effects of enhanced prehospital screening on triage, survival, and quality of life in TBI patients. Peters J , Van Wageningen B , Hoogerwerf N , Tan E . Near-infrared spectroscopy: a promising prehospital tool for management of traumatic brain injury. Prehosp Disaster Med. 2017;32(4):414-418.


The Change of Soluble Programmed Death Ligand 1 (sPD-L1) in Plasma of Small Cell Lung Cancer and Its Clinical Significance.
Background soluble programmed death-ligand 1 (sPD-L1) expression in lung squamous cell carcinoma and lung adenocarcinoma is associated with disease progression, and sPD-L1 expression in small cell lung cancer (SCLC) may have similar manifestations and become a potential marker for treatment. The purpose of this study was to observe the changes of plasma sPD-L1 expression in SCLC patients. Methods. 90 patients diagnosed with SCLC from January 2019 to November 2020 were selected as the test group, including 72 males and 18 women, 58.7 ± 6.6 years; 30 healthy subjects were selected from the physical examination center, including 18 males, 12 females, and 60.3 ± 7.0 years. There were no statistical difference in sex and age factors between the trial and control groups (p > 0.05). Selected SCLC used chemotherapy regimen: cisplatin + etoposide (EP), carboplatin + etoposide (CE), and SCLC group were divided into three subgroups of disease progression group, partial remission group, and disease stability group according to the treatment effect. Comparison of the differences in sPD-L1 expression content between the experimental and control populations. Plasma sPD-L1 levels were dynamically monitored pre- and posttreatment in 90 patients with small-cell lung cancer and were associated with efficacy among subgroups. Meanwhile, the risk factors for patient sPD-L1 expression content were analyzed by logistic regression. Results. Plasma sPD-L1 levels were higher in the SCLC group than in the healthy people group (t = 7.40, p < 0.01). In the disease progression group of the SCLC group, sPD-L1 levels were decreased in the SCLC group, sPD-L1 in some remission group was increased after treatment, and sPD-L1 levels in the disease-stable group (p > 0.05). Multivariate logistic regression analysis showed that factors promoting increased sPD-L1 expression in SCLC patients included increased smoking, brain metastasis, and ProGRP expression (both p values < 0.05). Conclusion. (1) Higher peripheral sPD-L1 expression in SCLC patients than in healthy patients, and the expression levels were closely related to efficacy. (2) Dynamic changes in s PD-L1 were correlated with clinical efficacy. (3) The progression of sPD-L1 and ProGRP in SCLC patients showed the same extent during remission and stabilization, suggesting the effect of s PD-L1 in the evaluation of SCLC tumors and the reflection of the tumor marker ProGRP.


Infantile malignant osteopetrosis: a rare cause of neonatal hypocalcemia.
Infantile malignant osteopetrosis (IMO; OMIM 259700) is a rare inherited bone disease characterized by reduced or dysregulated activity of osteoclasts, resulting in generalized osteosclerosis. The disease usually presents within the first few months of life with anemia, hepatosplenomegaly, frontal bossing, nystagmus, blindness, deafness, and bone fractures. Children with IMO are at risk of developing hypocalcemia, with attendant tetanic seizures. We report the case of a baby boy who presented with neonatal hypocalcemia. Skeletal radiographs demonstrated sclerotic bones and a dense base of the skull with typical "space alien" face confirming the diagnosis of IMO. Pancytopenia developed at 2 months of age. Visual evoked potential showed severe bilateral optic nerve damage. Genetic mutation study revealed a new mutation in exon 13 of the TCIRG1 gene. Neonatal hypocalcemia can occur as result of IMO, which is easily missed out by clinicians. This causes delay in establishing the diagnosis and starting necessary treatment. Therefore, osteopetrosis should be kept in mind as a rare cause of neonatal hypocalcemia.


Sex chromatin and chromosome numbers in Lepidoptera.
Three classes of sex chromatin (SC) distribution have been encountered in a sample of Canadian Lepidoptera. In 78 of the 103 species examined, females were SC positive and males were SC negative. In another 24 species, females and males were SC negative. Females and males of a single species, Eucordylea resinosae, had two equal-sized SC bodies in interphase nuclei. In no species were females found to be SC negative and males SC positive. Usually presence of SC indicates an XX male and XY female sex determining mechanism, and its absence, XX male; XO female, but the exceptional occurrence of SC in females and males of a species suggests the need for caution in too universal an application of this interpretation. Chromosome numbers have also been determined for 53 of the 103 species. Male haploid numbers ranged from 11 to 61, but 30 was most frequently encountered.


A study on the prevalence of hookworm infection in four districts of West Bengal and its linkage with anaemia.
Stool samples collected from the districts of Darjeeling, Jalpaiguri, Hooghly and Calcutta in West Bengal were examined for hookworm and associated parasites. It was found that maximum prevalence of hookworm was in Hooghly district (24.8%). N. americanus appeared to be more prevalent species in all the districts studied. The load ofhookworm infection appeared to be mostly in the mild range. Ascaris lumbricoides appeared to the most common accompanying infection. In the affected population, the degree of anaemia was mostly mild.


Improvement of the eradication rate of Helicobacter pylori gastritis in children is by adjunction of omeprazole to a dual antibiotherapy.
The possible improvement of efficacy and tolerability of a 7-day dual antibiotherapy amoxicillin-clarithromycin (AC) on the eradication of Helicobacter pylori (H. pylori) gastritis in children by the adjunction of omeprazole (OAC) was studied. Forty-six children presenting with H. pylori gastritis, assessed at inclusion by endoscopy, H. pylori urease test, histology and/or culture were randomised to a twice-daily regimen of AC or OAC. A (13)C-urease breath test was performed 4-6 weeks after the end of the treatment period to evaluate H. pylori eradication. A larger proportion of patients was H. pylori negative (69%) in the OAC regimen treatment 4-6 weeks after eradication treatment compared with those who received dual AC therapy (15%). A total of seven patients (three in the OAC and four in the AC group) reported adverse events (AEs). Only vomiting was reported in more than one patient (one in each treatment regimen) and only one AE was severe (urticaria: in the OAC group, but considered not related to treatment). A larger eradication rate of H. pylori was obtained in the triple OAC group than in the dual AC group. Both therapy regimens can be safely administered to children for 7 days.


Lactate in human sweat: a critical review of research to the present day.
This review provides a critical overview of the literature published in the area of lactate in human sweat between 1934 and the present. The first section summarizes the relevant pieces of literature, the second evaluates the literature across a range of topics and the third presents potential applications for sweat lactate measurements. Key factors that may affect sweat lactate are discussed in detail in the second section of this review. Both acetylcholine and catecholamine hormonal signals can trigger sweating independently of one another; differences in sweat output and lactate concentrations are compared. The primary triggers for sweating, exercise and heat are also compared, with exercise-induced sweating being further examined with respect to the exercise intensity. This review examines the significant variations in sweat lactate between bodily sites as well the relationship to physiological parameters such as gender, age and physical fitness, along with the effect of climate adaptation on sweat lactate concentrations.


The dynamics of sexual conflict over mating rate with endosymbiont infection that affects reproductive phenotypes.
Maternally inherited endosymbionts have been implicated as significant drivers of sexual conflict within their hosts, typically through sex-ratio manipulation. Empirical studies show that some of these endosymbionts have the potential to influence sexual conflict not by sex-ratio distortion, but by altering reproductive traits within their hosts. Research has already shown that reproductive traits involved in mating/fertilization process are integral 'players' in sexual conflict, thus suggesting the novel hypothesis that endosymbiont-induced changes in reproductive phenotypes can impact the dynamics of sexual conflict. Here, we use a standard quantitative genetic approach to model the effects of endosymbiont-induced changes in a female reproductive trait on the dynamics of sexual conflict over mating/fertilization rate. Our model shows that an endosymbiont-induced alteration of a host female reproductive trait that affects mating rate can maintain the endosymbiont infection within the host population, and does so in the absence of sex-ratio distortion and cytoplasmic incompatibility.


Is Hydatid Cyst with Musculoskeletal Involvement a Problem that Causes Morbidity? Long-Term Follow-Up and Functional Results.
The aim of study is to evaluate the involvement characteristics of hydatid cysts, which are rarely involved the musculoskeletal system, and the results of recurrence, morbidity, and functional and mental scoring. We retrospectively investigated 18 patients with skeletal hydatid disease. Patients were categorized as those with bone or skeletal muscle involvement. Pre- and post-operative physical component scores (PCS) and mental component scores (MCS) on the functional Short Form 12-item Survey were recorded in these patients.We compared the functional scores, number of recurrences, and lesion volumes between patients with hydatid cyst of bone (HCOB) and those with hydatid cyst of soft tissue (HCOST). This study included 11 women and 7 men with bone hydatid cysts. Patients' mean age was 38 years (range 22-70 years). Patients were followed up for a mean of 118.16 months (range 49-230 months). The mean lesion volume was 447.39 cm3 (36-1260 cm3). The 12th and 48th month PCS, the PCS was lower in the HCOB group during both periods (p = 0.04 and p = 0.001, respectively). The 48th month MCS was lower in the HCOB group (p = 0.04). Postoperative residual cysts were detected in five patients who underwent surgical treatment for bone c; all residual lesions were located in the pelvis. Bone hydatid cysts are associated with high recurrence rates, and treatment is challenging. In view of the low functional results and high infection and recurrence rates observed in patients over long-term follow-up, particularly in those with pelvic hydatid cysts, we conclude that this disease is associated with significant morbidity.


Properties of the duplex DNA-dependent ATPase activity of Escherichia coli RecA protein and its role in branch migration.
We have investigated the double-stranded DNA (dsDNA)-dependent ATPase activity of recA protein. This activity is distinguished from the single-stranded DNA (ssDNA)-dependent ATPase activity by the presence of a pronounced lag time before the onset of steady-state ATP hydrolysis. During the lag phase there is little ATP hydrolysis. The duration of the lag phase, referred to as the lag time, is found to increase with the thermal stability of the dsDNA substrate. Increasing either the MgCl2 or NaCl concentration increases the lag time, whereas increasing the temperature decreases the lag time. The lag time shows little dependence on recA protein concentration but is strongly dependent on ATP concentration. After the lag phase, a steady-state ATP hydrolysis rate is achieved that approaches the rate observed with ssDNA. The steady-state phase of the reaction is proportional to the concentration of recA protein-DNA complex and shows saturation behavior at approximately equal to 5 +/- 1 base pairs per recA protein monomer. These results suggest that the lag phase represents a rate-limiting step in the dsDNA-dependent ATP hydrolysis reaction that requires a structural transition in the dsDNA and that involves a ternary complex of ATP, recA protein, and DNA. We propose that this transition involves the transient denaturation of the dsDNA to form regions of ssDNA. Elsewhere we demonstrate that the dsDNA-dependent ATPase activity is proportional to the rate of recA protein-catalyzed branch migration. We suggest that this activity is responsible for a polar polymerization that drives the branch migration reaction.


Rationale for prescription, and effectiveness of, upper limb orthotic intervention for children with cerebral palsy: a systematic review.
To explore (i) reasons for upper limb orthosis prescription for children with cerebral palsy (CP), (ii) the link between reason and effect according to intended outcome and outcome measure utilized and (iii) to classify the prescribed orthoses using standard terminology. A prospectively registered (center for reviews and dissemination: 42015022067) systematic review searched for experimental and observational studies investigating rigid/thermoplastic upper limb orthotic intervention for children aged 0-18 with CP. The Cochrane central register, MEDLINE, CINAHL, Embase, SCOPUS and Web of Science databases were searched. Included studies were assessed for risk of bias. Sixteen studies met selection criteria. Two studies described a specific reason for orthosis prescription, six prescribed orthoses to manage a clinical symptom and eight did not describe a reason. Eight studies were analyzed for effect according to intended outcome with no clear connection found between reasons for prescription, outcome measures utilized and effect reported. The lack of evidence for upper limb orthotic intervention for children with CP leads to uncertainty when considering this treatment modality. Future research is needed to evaluate the effect of orthosis wear in relation to intended outcome utilizing robust methods and valid and reliable outcome measures. Implications for rehabilitation: Insufficient evidence exists about the reason for prescription of upper limb orthoses. The connection between reason for orthosis prescription, intended outcome, outcome measure utilized and observed effect is unclear. Recommend orthosis prescription to be accompanied by clear documentation of the aim of the orthosis and description using orthosis classification system terminology. Outcome measures consistent with the reason for orthosis prescription and intended outcome of the intervention are essential to measure effectiveness of the intervention.


Water availability as dominant control of heat stress responses in two contrasting tree species.
Heat waves that trigger severe droughts are predicted to increase globally; however, we lack an understanding of how trees respond to the combined change of extreme temperatures and water availability. Here, we studied the impacts of two consecutive heat waves as well as post-stress recovery in young Pseudotsuga menziesii (Mirb.) Franco (Douglas-fir) and Robinia pseudoacacia L. (black locust) growing under controlled conditions. Responses were compared under water supply close to the long-term average and under reduced irrigation to represent drought. Exposure to high temperatures (+10 °C above ambient) and vapour pressure deficit strongly affected the trees in terms of water relations, photosynthesis and growth. Douglas-fir used water resources conservatively, and transpiration decreased in response to mild soil water limitation. In black locust, heat stress led to pronounced tree water deficits (stem diameter shrinkage), accompanied by leaf shedding to alleviate stress on the hydraulic system. The importance of water availability during the heat waves became further apparent by a concurrent decline in photosynthesis and stomatal conductance with increasing leaf temperatures in both species, reaching the lowest rates in the heat-drought treatments. Stress severity determined both the speed and the amount of recovery. Upon release of stress, photosynthesis recovered rapidly in drought-treated black locust, while it remained below control rates in heat (t = -2.4, P < 0.05) and heat-drought stressed trees (t = 2.96, P < 0.05). In Douglas-fir, photosynthesis recovered quickly, while water-use efficiency increased in heat-drought trees because stomatal conductance remained reduced (t = -2.92, P < 0.05). Moreover, Douglas-fir was able to compensate for stem-growth reductions following heat (-40%) and heat-drought stress (-68%), but most likely at the expense of storage and other growth processes. Our results highlight the importance of studying heat waves alongside changes in water availability. They further suggest that we should look beyond the actual stress event to identify lagged effects and acclimation processes that may determine tree resilience in the long term.


Redo pull-through for postoperative complications following pull-through in Hirschsprung disease: a single center experience.
Although surgical management of Hirschsprung disease (HD) is effective in most patients, some patients experience long-term postoperative complications, and require redo pull-through (PT). The present study evaluated clinical outcomes of redo PT in HD patients at a single center. Patients with HD who underwent redo PT procedures between 2003 and 2019 were retrospectively reviewed. Thirteen patients were included. Five (38.5%) had undergone initial PT surgery at our center and 8 (61.5%) at other centers. Redo PT procedures were transanal endorectal PT in 12 patients (92.3%) and the posterior sagittal approach in 1 patient (7.7%). Indications for redo PT included pathologic misdiagnosis in 8 patients (61.5%); stricture in 2 (15.4%); and rectal stenosis, obstructing Duhamel pouch and remnant septum in 1 each (7.7%). At a median follow-up of 68 months (range, 3-227 months) after redo PT, 8 patients (61.5%) had normal bowel function, 2 (15.4%) had incontinence, and 1 (7.7%) had constipation. Redo PT procedures could be an effective approach for improving obstructive symptoms in HD patients with anatomic or pathologic reasons following primary PT. Careful selection of patients and discreet indications for redo PT are crucial.


Probiotics as functional foods.
Probiotic products have been widely used in Japan and Europe for years. Probiotics are now emerging as an important category of food supplement in the United States. Questions about the biologic nature, available products, claimed health benefits, and safety and regulation of probiotics are important for both consumers and nutrition professionals. Probiotics can be considered functional foods because they provide health benefits beyond the traditional nutrition function. With few exceptions, most probiotic products currently available contain lactic-acid-producing bacteria, which mainly belong to the genera Lactobacillus and Bifidobacterium. We reviewed the scientific papers published in major nutrition journals and abstracts available on the PubMed website regarding probiotics. Evidence suggests the following beneficial effects of probiotics: normalization of the intestinal microflora, ability to block the invasion of potential pathogens in the gut, prophylactic or therapeutic treatment for several types of diarrhea, relief of symptoms of irritable bowel syndrome and inflammatory bowel disease, amelioration of lactose intolerance, prevention of colon cancer, modulation of immune function, inhibition of Helicobacter pylori, and possible enhancement of calcium absorption and reduction of blood cholesterol levels. Mechanisms for the above benefits have been proposed, but none has been proven. An adequate level of viable bacteria in a probiotic product and an appropriate daily dose are critical to achieve a health benefit. Because probiotics are not known to be pathogenic and their upper tolerable level is high, they could be promoted as a beneficial food supplement. Currently, no disease-prevention or therapeutic claim for probiotics is legally allowed.


Incidence and predictors of severe altitude illness symptoms in Mt. Kilimanjaro hikers: a prospective cohort study.
Each year several Mt. Kilimanjaro hikers die due to altitude illness (AI) although urgent descent is technically easily possible. The objectives of this study were to determine the incidence and predictors of severe altitude illness (SAI) symptoms and of summit success in Mt. Kilimanjaro hikers, and the measures taken when AI symptoms develop. A prospective observational cohort study in Mt. Kilimanjaro hikers was conducted from December 2019 until March 2020. Participants were asked to complete a questionnaire at the entrance gate and one at the descend gate. A multivariate logistic regression was performed to study the relations between the variables. A total of 1237 recreational hikers and 266 porters or guides were included. The incidence of severe symptoms was 8.6% in recreational hikers and 1.5% in porters and guides. One percent (1.1%) of hikers was hospitalized due to SAI. A history of SAI, young age, summit failure and lack of clear advice predicted the development of severe symptoms. Uhuru peak was reached by 87.9% of the hikers. Absence of severe symptoms, acetazolamide prophylaxis, climbing higher in daytime, young age and climbing in more days predicted summit success. The majority climbed further despite the presence of mild or severe symptoms. The only measure taken in case of mild symptoms that was associated with a lower incidence of severe symptoms was not climbing further. The incidence of SAI symptoms in Mt. Kilimanjaro hikers was observed to be high. However, how hikers reacted during symptoms was not appropriate. Therefore, travel health counsellors should emphasize even more that hikers do not ascend higher until mild symptoms have resolved and that it is vital to descend immediately when severe symptoms develop. In addition, they can be informed on the measures, which improved summit success.


Application of Artificial Intelligence in Drug-Drug Interactions Prediction: A Review.
Drug-drug interactions (DDI) are a critical aspect of drug research that can have adverse effects on patients and can lead to serious consequences. Predicting these events accurately can significantly improve clinicians' ability to make better decisions and establish optimal treatment regimens. However, manually detecting these interactions is time-consuming and labor-intensive. Utilizing the advancements in Artificial Intelligence (AI) is essential for achieving accurate forecasts of DDIs. In this review, DDI prediction tasks are classified into three types according to the type of DDI prediction: undirected DDI prediction, DDI events prediction, and Asymmetric DDI prediction. The paper then reviews the progress of AI for each of these three prediction tasks in DDI and provides a summary of the data sets used as well as the representative methods used in these three prediction directions. In this review, we aim to provide a comprehensive overview of drug interaction prediction. The first section introduces commonly used databases and presents an overview of current research advancements and techniques across three domains of DDI. Additionally, we introduce classical machine learning techniques for predicting undirected drug interactions and provide a timeline for the progression of the predicted drug interaction events. At last, we debate the difficulties and prospects of AI approaches at predicting DDI, emphasizing their potential for improving clinical decision-making and patient outcomes.


[A Case of Carotid Free-Floating Thrombus Treated by Carotid Ultrasonography-Guided Endovascular Approach].
We experienced a case of carotid free-floating thrombus treated by carotid ultrasonography-guided endovascular approach. A 63-year-old man was brought to our hospital with the chief complaint of sudden onset left hemiplegia. MRI revealed acute infarction of the right MCA territory due to the right M1 occlusion. Carotid ultrasonography showed a pedunculated, polypoid mobile plaque floating with the cardiac beat. We attempted ultrasonography-guided endovascular treatment. Under proximal balloon protection, the floating plaque was successfully aspirated into the Penumbra aspiration catheter. Carotid stent was also placed to stabilize the residual pedicle of the plaque. Aspirated plaque was identified as fresh thrombus by pathological examination. Carotid ultrasonography-guided endovascular approach was effective for getting the picture of real-time dynamics of the carotid FFT.


Communicable and non-communicable diseases in the Solomon Islands villages during recovery from a massive earthquake in April 2007.
The major causes of mortality and morbidity have changed from infectious diseases and malnutrition conditions to non-communicable diseases (NCDs) in Melanesian societies. However, a massive earthquake and its related changes might have disturbed the patterns. This study aimed to explore which health problems were likely to be prevalent during the recovery process from the 2 April 2007 earthquake in the Solomon Islands. Participants were recruited in Titiana, a severely damaged village located near a town; Tapurai, a severely damaged remote village; Mondo, a severely damaged, medium urban village; and Olive, a control village. Health indicators measured were classified into communicable and nutritional conditions (malaria, malnutrition, infection status and child growth) and NCDs (overweight/obesity, hypertension and diabetes). Titiana residents were more at risk of infectious conditions (C-reactive protein greater than and equal to 1 mg/dL) and obesity (BMI greater than and equal to 30 kg/m²). Tapurai and Mondo residents were at risks of infectious conditions and becoming overweight (BMI greater than and equal to 25 kg/m²), respectively. Titiana and Mondo residents complained about insufficient subsistence production. The urban communities were found to be at risks of both communicable and NCDs. Controlling the urbanisation as well as providing continuous support against infectious conditions during the recovery process would be beneficial.


[The study of continuous arterial infusion chemotherapy with 5-FU and CDDP in patients with hepatocellular carcinoma].
Between Feb. 1992 and March in 1994, 14 patients with hepatocellular carcinoma (7: recurrence, 7: unresectable) received continuous arterial infusion of 5-FU and CDDP via implanted reservoir. For the next five days, 10 mg/body of CDDP and 250 mg/body of 5-FU using arterial infusion were administered. It was discontinued for two days, as one course, and 4 courses were basally administered. The duration of the administration was 24 or 6 hours/day. Side effects consisted of nausea or loss of appetite for 7 (50%), suppression of bone marrow for 3 (21%), and they disappeared after the agents were discontinued. However, there were 3 patients with gastro-duodenal ulcer, so careful follow-up was necessary. The efficacy rate was 64% and two-year survival rate was 57% and thus this treatment seemed to be effective. Further study on the duration and dose of the administration is necessary to improve the therapeutic effect and QOL.


HPLC-MS/MS method for the determination of cytarabine in human plasma.
Cytarabine is an anti-tumor drug that is currently under investigation for treatment in combination with other anticancer drugs for the chemotherapy of leukemia. The quantitative determination of cytarabine in plasma is challenging due to the required sensitivity, its in vitro instability and the presence of an isobaric endogenous compound, cytidine. Owing to the polarity of cytarabine, conventional chromatography cannot provide adequate separation of the analyte and the interfering compounds. A few analytical methods have been reported for the determination of cytarabine in plasma, but their sensitivity was not sufficient since most of these methods apply spectrophotometric detection. In this article, an LC-MS/MS method is described for the determination of cytarabine in human plasma down to the sub ng/ml level. To prevent conversion of cytarabine by cytidine deaminase, whole blood samples were stabilized with tetrahydrouridine directly after the collection of whole blood at the clinical site. Cation-exchange SPE was employed to extract cytarabine from 50 µl human plasma. UHPLC on high strength silica T3 column (100 × 2.1 mm × 1.8 µm) was applied to achieve adequate separation of cytarabine from cytidine within a reasonable run time of 5 min. A triple quad mass spectrometer equipped with an ESI source was used for detection. The method was linear over the concentration ranges of 0.500-500 ng/ml. The intra- and inter-day relative standard deviation (precision) as well as the bias (accuracy) were well below 15%. In the presence of tetrahydrouridine, cytarabine was sufficiently stable under all relevant conditions. The method was successfully applied to support a clinical pharmacokinetic study with a low dose of cytarabine.


Production of interleukin-6 in vitro parallels development of cytotoxic T lymphocytes from murine thymocytes.
In an attempt to provide information useful for improving tumor immunotherapy, we examined the lymphokine requirements for generation of cytotoxic T lymphocytes (CTL) from C57BL/6 murine thymocytes. Our previous work indicated that interleukin-6 (IL-6) is involved in the maturation of CTL in vitro. Using a standard chromium 51 release assay and P815 mastocytoma tumor cells as targets, we found that after 66 hours of in vitro culture, a much greater CTL response was generated in the presence of interleukin-2 (IL-2) plus IL-6 (70.5% +/- 10.6%) compared with that generated in the presence of IL-2 only (25.2% +/- 1.0%). After 72 hours of culture, however, this difference was no longer significant, with cultures incubated with both IL-2 and IL-6 yielding 70.6% +/- 1.8% lysis versus 64.5% +/- 3.4% for cultures incubated with IL-2 only. To attempt to understand this difference, we examined the production of IL-6 in thymocyte cultures using a cell line, PC-6, that proliferates in the presence of IL-6. We found that the CTL response generated from unfractionated murine thymocytes in the presence of concanavalin A plus IL-2 correlated with production of IL-6 by cells within the thymic population. These data suggest that the generation of a CTL response in the absence of added IL-6 is due to the production of this ubiquitous lymphokine by thymocytes on in vitro culture. We present this as further evidence that IL-6 is necessary for the development of functional CTL from murine thymocytes and may therefore play a role in the development of effective tumor immunotherapy.


Role of reactive nitrogen intermediate production in alveolar macrophage-mediated cytostatic activity induced by bleomycin lung damage in rats.
Bleomycin (BLM) is a useful anticancer agent sometimes associated with a diffuse pulmonary inflammation and fibrosis. Using an intratracheal model of BLM-induced pulmonary damage, we have further investigated alveolar macrophage (AM) activation following intratracheal BLM. From rats that had been treated with either a single, fibrogenic, intratracheal dose of BLM (BLM-AM) or a comparable volume of saline (C-AM), bronchoalveolar lavage fluid was collected, and AM were isolated using Percoll gradient centrifugation. Using a spectrophotometric assay, production of nitrites by AM was measured. C-AM released low levels of nitrites, whereas BLM-AM as well as C-AM activated in vitro with lipopolysaccharide released significant amounts of nitrites. The addition of N6-monomethylarginine, a substrate-specific inhibitor of the L-arginine-dependent effector mechanism in activated macrophages, reduced the amount of measurable nitrites released from both BLM-AM and activated C-AM. Similar results were observed when 12 x 10(6) RBC were added to the cocultures. In the presence of N6-monomethylarginine, BLM-AM had no effect on two consequences of BLM-AM-induced cytostatic activity, DNA synthesis inhibition and aconitase activity reduction in the L1210 target cell. These results suggest that reactive nitrogen intermediates measured as nitrites are important moieties in our in vivo model of macrophage activation. Further, the identification of this effector molecule presents possibilities for therapeutic and biochemical manipulations.


Current treatment of recurrent vasovagal syncope: between evidence-based therapy and common sense.
Vasovagal syncope is very frequent and benign and the vast majority of subjects do not need any specific treatment, but only reassurance and education. An unknown but small percentage of patients require specific treatment when syncope is very frequent or is responsible for major trauma. For these patients, there are some evidence-based therapies available and some first-line treatments appear to be established. The therapeutic choice mainly depends on the presence and duration of prodromal symptoms. In subjects aged < 70 years with well recognizable prodromes, the first-line treatment is counterpressure manoeuvres. In patients with no or minimal prodromes, but with tilt testing and carotid sinus massage (CSM) both positive, cardiac pacing appear to be the first-line therapy. However, an area of uncertainty remains, represented by patients with no or minimal prodromes and negative CSM. For these patients, appropriate treatment (drugs, tilt training, cardiac pacing, relaxation-based treatment) can be chosen by considering the clinical context, the risk of trauma and possible comorbidities, in addition to utilizing the little or controversial knowledge available, as well as common sense.


Turkish validity and reliability study of the Weiss Functional Impairment Rating Scale-Parent Report.
Attention deficit hyperactivity disorder (ADHD) is seen frequently in childhood and leads to marked impairment in functioning. There is no scale in Turkey with documented validity and reliability that assesses ADHD-specific functional impairment (FI). This study aimed at adapting the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P), which assesses ADHD-related FI, for use in Turkey, and examining psychometric aspects of the scale. The study included 250 children diagnosed with ADHD and 250 healthy children and their parents. Internal consistency and test-retest methods were used to test the reliability of the scale. Validity was tested with exploratory and confirmatory factor analyses and convergent and discriminant validity analyses. Since all six questions of the WFIRS-P were scored 0, analyses were conducted for the original scale questionnaire consisting of 50 items and the questionnaire consisting of 44 items where the six questions scored 0 were not included. The Cronbach's alpha coefficient was 0.93 for the whole scale. The Spearman's correlation coefficient was 0.93 for test-retest reliability. The exploratory factor analysis run on the 44-item questionnaire showed that the scale items were best represented in a 7-factor structure, but some items were placed in different subdomains than those of the original scale. In the confirmatory factor analysis, the root mean square error of approximation was 0.061, and the comparative fit index was 0.95 for the whole model. Therefore, the Turkish WFIRS-P is valid and reliable in testing functional impairment in children with ADHD.


Dynamics of normal and superfluid fogs using diffusing-wave spectroscopy.
The dynamics of normal and superfluid fogs are studied using the technique of diffusing-wave spectroscopy. For a water fog generated with a 1.75 MHz piezoelectric driver below the liquid surface, the 7 microm diameter droplets are found to have diffusive dynamics for correlation times long compared to the viscous time. For a fog of 10 microm diameter superfluid helium droplets in helium vapor at 1.5 K the motion appears to be ballistic for correlation times short compared to the viscous time. The velocity correlations between the helium droplets are found to depend on the initial velocity with which the droplets are injected from the helium surface into the fog.


Vascular Remodeling, Oxidative Stress, and Disrupted PPARγ Expression in Rats of Long-Term Hyperhomocysteinemia with Metabolic Disturbance.
Hyperhomocysteinemia, a risk factor for vascular disease, is associated with metabolic syndrome. Our study was aimed at exploring the effect of long-term hyperhomocysteinemia with metabolic disturbances on vascular remodeling. We also studied oxidative stress and expression of PPARγ in the coronary arteriole as a possible mechanism underlying vascular remodeling. Rats were treated with standard rodent chow (Control) or diet enriched in methionine (Met) for 48 weeks. Plasma homocysteine, blood glucose, serum lipids, malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) levels were measured. Coronary arteriolar and carotid arterial remodeling was assessed by histomorphometric techniques and the expression of PPARγ in vessel wall was investigated. In Met group, an increase in the level of fasting blood glucose, serum triglyceride, total cholesterol, MDA, and NO, a decline in the serum SOD level, and increased collagen deposition in coronary and carotid arteries were found. Moreover, we detected decreased expression of PPARγ in the coronary arterioles in Met group. In summary, our study revealed metabolic disturbances in this model of long-term hyperhomocysteinemia together with vascular remodeling and suggested that impaired oxidative stress, endothelium dysfunction, and decreased PPARγ expression in the vessel wall could be underlying mechanisms.


Effects of anthocyanidins and anthocyanins on the expression and catalytic activities of CYP2A6, CYP2B6, CYP2C9, and CYP3A4 in primary human hepatocytes and human liver microsomes.
Anthocyanidins and anthocyanins are pharmacologically active constituents of various berry fruits, such as blueberry and cranberry. These compounds are also contained in massively used nutritional supplements based on extracts or dry matter from berry fruits. The current study evaluated the effects of anthocyanidins and anthocyanins on the expression and catalytic activity of major drug-metabolizing enzymes CYP2C9, CYP2A6, CYP2B6, and CYP3A4 in primary cultures of human hepatocytes and human liver microsomes. Expression of mRNA was quantified by qRT-PCR. Expression of proteins was evaluated by Western blotting and immunochemiluminescence. The catalytic activity of CYP enzymes was measured by HPLC using specific enzyme substrates. Tested anthocyanidins (6) and anthocyanins (21) did not induce the expression of mRNA and protein of CYP2C9, CYP2A6, CYP2B6, and CYP3A4 genes in human hepatocytes. Catalytic activities of CYP2C9, CYP2A6, CYP2B6, and CYP3A4 enzymes were inhibited by all anthocyanidins to different extents (e.g., delphinidin inhibits CYP3A4 by >90% at 100 μM with IC50 = 32 μM). Of 21 anthocyanins tested, only cyanidin-3-O-rhamnoside (CYP3A4 by >75% at 100 μM with IC50 = 44 μM) and two glycosides of delphinidin significantly inhibited examined cytochromes P450. It may be concluded that in the ranges of common ingestion of either food or dietary supplement an induction or significant inhibition of CYP2C9, CYP2A6, CYP2B6, and CYP3A4 activity is most probably not expected.


A Novel Method for Identifying Essential Proteins Based on Non-negative Matrix Tri-Factorization.
Identification of essential proteins is very important for understanding the basic requirements to sustain a living organism. In recent years, there has been an increasing interest in using computational methods to predict essential proteins based on protein-protein interaction (PPI) networks or fusing multiple biological information. However, it has been observed that existing PPI data have false-negative and false-positive data. The fusion of multiple biological information can reduce the influence of false data in PPI, but inevitably more noise data will be produced at the same time. In this article, we proposed a novel non-negative matrix tri-factorization (NMTF)-based model (NTMEP) to predict essential proteins. Firstly, a weighted PPI network is established only using the topology features of the network, so as to avoid more noise. To reduce the influence of false data (existing in PPI network) on performance of identify essential proteins, the NMTF technique, as a widely used recommendation algorithm, is performed to reconstruct a most optimized PPI network with more potential protein-protein interactions. Then, we use the PageRank algorithm to compute the final ranking score of each protein, in which subcellular localization and homologous information of proteins were used to calculate the initial scores. In addition, extensive experiments are performed on the publicly available datasets and the results indicate that our NTMEP model has better performance in predicting essential proteins against the start-of-the-art method. In this investigation, we demonstrated that the introduction of non-negative matrix tri-factorization technology can effectively improve the condition of the protein-protein interaction network, so as to reduce the negative impact of noise on the prediction. At the same time, this finding provides a more novel angle of view for other applications based on protein-protein interaction networks.


Endocarditis caused by Lactococcus cremoris.
We describe a case of subacute endocarditis due to Lactococcus cremoris associated with consumption of unpasteurized milk. Treatment with amoxicillin-clavulanic acid and subsequently penicillin resulted in prompt sterilization of this patient's bloodstream and full recovery.