Occult diaphragmatic injuries caused by stab wounds.
Missed diaphragmatic perforation caused by penetrating trauma can lead to subsequent strangulation of a hollow viscus, which has prompted the use of invasive diagnostic procedures to exclude occult diaphragmatic injuries in asymptomatic, high-risk patients. The objective of this study was to determine the incidence of occult diaphragmatic injuries caused by stab wounds of the lower chest and upper abdomen, and to examine the natural history and consequences of missed diaphragmatic injuries. On the basis of patient data from two previous randomized studies from our institution, a retrospective analysis was performed on 97 patients treated for anterior stab wounds located between the nipple line, the umbilical level, and the posterior axillary lines not having indications for immediate surgical exploration. The patients were divided into two groups on the basis of their initial randomized management (open or laparoscopic exploration vs. expectant observation). In the exploration group (n = 47), four diaphragmatic injuries (9%) were detected (three left-sided and one right-sided). Excluding patients with associated injuries requiring surgical repair, the incidence of occult diaphragmatic injuries was 3 of 43 (7%). In the observation group (n = 50), there were two patients (4%) with delayed presentation of missed left-sided diaphragmatic injury 2 and 23 months later, respectively. Both injuries resulted from stab wounds of the left flank and presented with herniation of the stomach or small bowel and colon. The overall incidence of occult diaphragmatic injuries in left-sided thoracoabdominal stab wounds was 4 of 24 (17%), and was much lower after stab wounds of left epigastrium (0%), right lower chest (0%), and right epigastrium (4%). In asymptomatic patients with anterior or flank stab wounds of the lower chest or upper abdominal area, the risk of an occult diaphragmatic injury is approximately 7% which, if undetected, is associated with a high risk of subsequent hollow viscus herniation. Exclusion of an occult diaphragmatic injury with invasive diagnostic methods, such as laparoscopy or thoracoscopy, should be considered at least in left-sided stab wounds of the lower chest.


Influence of cyclic nucleotides on junctional permeability in atrial muscle.
The influence of dB-cAMP (5 X 10(-4) M) and 8-Br-cGMP (5 X 10(-5) M; 5 X 10(-9) M) on the longitudinal diffusion of Lucifer Yellow CH along dog trabeculae was investigated. It was found that dB-cAMP enhances the diffusion coefficient of the dye from 4 +/- 0.63 X 10(-7) cm2/s (control) to 2 +/- 0.53 X 10(-6) cm2/s. Efflux studies showed that the permeability of the surface cell membrane to Lucifer Yellow is negligible ruling out the possibility that the dye moved from cell-to-cell through the extracellular space. The permeability of the nexal membrane (Pnexus = 3 X 4 cm/s) was appreciably enhanced in fibers exposed to dB-cAMP (9.1 X 10(-4) cm/s). No change in the longitudinal redistribution of Lucifer Yellow CH was found with 8-Br-cGMP. The results support the hypothesis that cAMP is a modulator of junctional permeability in the normal heart.


Clinical features of snake envenomation in South Korea.
Three venomous snakes of the Gloydius genus belonging to the Viperidae family cause most snake envenomations in South Korea. Envenomation signs often include local swelling, coagulopathy, and rhabdomyolysis. The benefit of additional antivenom after the initial does is unclear. This retrospective study divided patients into four groups according to the presence of rhabdomyolysis (creatine kinase ≥1000 IU/L) and coagulopathy, which were defined using the Korean Society on Thrombosis and Hemostasis disseminated intravascular coagulation score (rhabdomyolysis, coagulopathy, combination, and local effects groups). We describe the clinical features of envenomation and the antivenom response. Greater local swelling predicted more severe snakebite pain. Ninety of the 231 enrolled patients (38.9%) developed rhabdomyolysis. The patients with severe rhabdomyolysis in the combination group displayed higher peak creatine kinase activity than the rhabdomyolysis group. Seven patients with rhabdomyolysis, including two patients requiring kidney replacement therapy, developed acute kidney injury, but the incidence of acute kidney injury did not differ between the combination group and rhabdomyolysis group. Bleeding developed in 3.5% of the patients, but its incidence did not differ between the combination and coagulopathy groups. Approximately half of all patients needed repeated antivenom administration, mainly due to the local envenomation effect. Earlier administration of additional antivenom for progressive local swelling did not reduce the hospitalization duration. Rhabdomyolysis is one of the major effects of Gloydius snake envenomation in South Korea, although it is not associated with the same risk of clinical deterioration as coagulopathy. Additionally, the ability of antivenom to ameliorate local swelling should be investigated to prevent unnecessary antivenom administration in South Korea.


Amphetamine-type Stimulants: Novel Insights into their Actions and use Patterns.
This review focuses on the effects and mechanisms of action of amphetamine-type stimulants (ATS) and their adverse effects on the cardiovascular, nervous, and immune systems. ATS include amphetamine (AMPH), methamphetamine (METH, "crystalmeth," or "ice"), methylenedioxymethamphetamine (MDMA, "ecstasy," or "Molly"), MDMA derivatives (e.g., methylenedioxyamphetamine [MDA] and methylenedioxy-N-ethylamphetamine [MDEA]), khat, and synthetic cathinones. The first section of this paper presents an overview of the historical aspects of ATS use, their initial clinical use, and regulations. The second part reviews the acute and chronic impact and the most salient clinical effects of ATS on the central nervous and cardiovascular systems, skin, and mouth. The chemical structure, pharmacokinetics, and classic and non-canonical pharmacological actions are covered in the third section, briefly explaining the mechanisms involved. In addition, the interactions of ATS with the central and peripheral immune systems are reviewed. The last section presents data about the syndemic of ATS and opioid use in the North American region, focusing on the increasing adulteration of METH with fentanyl.


Reducing the risk of nipple necrosis: technical observations in 340 nipple-sparing mastectomies.
Optimizing cosmesis is a common goal of breast surgery. In support of immediate breast reconstruction, nipple-sparing techniques have evolved. There is still a lack of agreement on the optimal technique and skin flap necrosis can be problematic. In this study, we review our experience with 340 NSM. Between March 2006 and February 2011, 340 NSMs were performed. Mammography, ultrasonography and magnetic resonance imaging were reviewed. Patient demographics and surgical techniques were reviewed. Anatomic observations were made and supported by breast images. A total of 340 NSMs in 231 patients by a single surgeon (AJS) were reviewed. Risk reduction was the indication for surgery in 59% with 50 patients (21.6%) testing positive for a BRCA1/2 gene mutation. There were two flap losses and 14 hematomas. Complete nipple necrosis occurred in three cases (0.8%) and partial loss in six patients. Recommendations are made to reduce the risk of nipple necrosis included the following: (a) preserving major perforating vessels (b) elevating skin flaps in the plane between the subcutaneous fat and the breast glandular tissue (c) the use of incisions that do not devascularize the nipple-areola complex. Nipple-sparing mastectomy can be performed with an acceptably low risk of nipple necrosis. Attention to detail including preserving major perforating vessels, elevating skin flaps in the appropriate plane and careful attention to incision planning are all required for a consistently good cosmetic outcome.


Integration within and between muscles during terrestrial locomotion: effects of incline and speed.
Animals must continually adapt to varying locomotor demands when moving in their natural habitat. Despite the dynamic nature of locomotion, little is known about how multiple muscles, and different parts of a muscle, are functionally integrated as demand changes. In order to determine the extent to which synergist muscles are functionally heterogeneous, and whether this heterogeneity is altered with changes in demand, we examined the in vivo function of the lateral (LG) and medial (MG) gastrocnemius muscles of helmeted guinea fowl (Numida meleagris) during locomotion on different inclines (level and uphill at 14 degrees ) and at different speeds (0.5 and 2.0 m s(-1)). We also quantified function in the proximal (pMG) and distal (dMG) regions of the MG to examine the extent to which a single muscle is heterogeneous. We used electromyography, sonomicrometry and tendon force buckles to quantify activation, length change and force patterns of both muscles, respectively. We show that the LG and MG exhibited an increase in force and stress with a change in gait and an increase in locomotor speed, but not with changes in incline. While the LG and MG exhibited similar levels of stress when walking at 0.5 m s(-1), stress in the LG was 1.8 times greater than in the MG when running at 2.0 m s(-1). Fascicle shortening increased with an increase in speed on both inclines for the LG, but only on the level for the pMG. Positive work performed by the LG exceeded that of the pMG and dMG for all conditions, and this difference was magnified when locomotor speed increased. Within the MG, the pMG shortened more, and at a faster rate than the dMG, resulting in a greater amount of positive work performed by the pMG. Mean spike amplitude of the electromyogram (EMG) bursts increased for all muscle locations with an increase in speed, but changes with incline were more variable. The functional differences between the LG and MG are likely due to the different moments each exerts at the knee, as well as differences in motor unit recruitment. The differences within the MG are likely due to motor unit recruitment differences, but also differences in architecture. Fascicles within the dMG insert into an extensive aponeurosis, which results in a higher apparent dynamic stiffness relative to fascicles operating within the pMG. On the level surface, the greater compliance of the pMG leads to increased stretch of its fascicles at the onset of force, further enhancing force production. Our results demonstrate the capacity for functional diversity between and within muscle synergists, which occur with changes in gait, speed and grade.


Risk of secondary malignancies after radiation therapy for breast cancer: Comprehensive results.
To assess risks of secondary malignancies in breast cancer patients who received radiation therapy compared to patients who did not. The SEER database was used to identify females with a primary diagnosis of breast cancer as their first malignancy, during 1973-2008. We excluded patients with metastatic disease, age <18 years, no definitive surgical intervention, ipsilateral breast cancer recurrence, or who developed a secondary malignancy within 1 year of diagnosis. Standardized incidence ratios and absolute excess risk were calculated using SEER*Stat, version 8.2.1 and SAS, version 9.4. There were 374,993 patients meeting the inclusion criteria, with 154,697 who received radiation therapy. With a median follow-up of 8.9 years, 13% of patients (49,867) developed a secondary malignancy. The rate of secondary malignancies was significantly greater than the endemic rate in breast cancer patients treated without radiation therapy, (O/E 1.2, 95% CI 1.19-1.22) and with radiation therapy (O/E 1.33, 95% CI 1.31-1.35). Approximately 3.4% of secondary malignancies were attributable to radiation therapy. The increased risk of secondary malignancies in breast cancer patients treated with radiation therapy compared to those without was significant regardless of age at breast cancer diagnosis (p < 0.01) and more pronounced with longer latency periods. There was an increased risk of secondary malignancies for breast cancer patients both with and without radiation therapy compared to the general population. There was an increased risk in specific sites for patients treated with radiation therapy. This risk was most evident in young patients and who had longer latency periods.


Student Voices: Perspectives on Peer-to-Peer Sexual Health Education.
This process study is a companion to a randomized evaluation of a school-based, peer-led comprehensive sexual health education program, Teen Prevention Education Program (Teen PEP), in which 11th- and 12th-grade students are trained by school health educators to conduct informative workshops with ninth-grade peers in schools in North Carolina. The process study was designed to understand youth participants' perspectives on the program in order to gain insight into program effectiveness. This is a mixed-methods study in 7 schools, with online surveys (N = 88) and 8 focus groups with peer educators (N = 116), end-of-program surveys (N = 1122), 8 focus groups with ninth-grade workshop participants (N = 89), and observations of the Teen PEP class and workshops during the semester of implementation in each school, 2012-2014. Both peer educators and ninth graders perceived benefits of participating in Teen PEP across a range of domains, including intentions, skills, and knowledge and that the peer education modality was important in their valuation of the experience. Our findings suggest that the peer-led comprehensive sexual health education approach embodied in Teen PEP can be an important educational mechanism for teaching students information and skills to promote sexual health.


Vibramycin in paediatrics. An evaluation of the onset of action and efficacy.
The effectiveness of and tolerance to doxycycline (Vibramycin, Pfizer) was investigated in a group of 188 children and the radpidity of both subjective and objective improvement was assessed in a second group of 58 children. Doxycycline was found to be very effective. It was possible to analyse the results of treatment in 245 out of the total of 246 patients. Cure was obtained in 168 patients (68.6%) and marked improvement was seen in 59 (24.1%). The overall success rate was thus 92.7%. 18 patients (7.3%) failed to respond; these either had a history of relapsing infections or were infected with resistant organisms. Doxycycline also proved to be rapid in its effect. Rapid subjective improvement was seen in 48 out of 58 patients (84.2%) and rapid objective improvement in 41 patients (70.7%). Tolerance to doxycycline was very good. Treatment had to be interrupted in only one out of 246 patients; there were initial gastrointestinal symptoms in 4 patients. Doxycycline showed itself to be a very suitable antibiotic for use in day-to-day paediatric practice.


Comparison of a foam rolling session with active joint motion and without joint motion: A randomized controlled trial.
Foam rolling has become a popular form of self-myofascial release or roller massage among health and fitness professionals. Due to this popularity, foam roller devices can be found in many clinical and fitness settings. Despite the popularity, there are still several unknowns regarding foam rolling such the optimal technique. Specifically, there is a lack of research analyzing different foam roll techniques such as combining active joint motion with foam rolling. The purpose of this study was to compare the effects of a foam rolling session to the left quadriceps with active joint motion and without joint motion on passive knee flexion range of motion (ROM) and pressure pain thresholds (PPT). Thirty healthy adults were randomly allocated to one of two intervention groups: active joint motion and no joint motion. Each foam roll intervention to the left quadriceps lasted a total of 2 min. Dependent variables included passive knee flexion ROM and pressure pain threshold measures (PPT). Statistical analysis included subject demographic calculations and appropriate parametric and non-parametric tests to measure changes within and between intervention groups. For left knee ROM, the active joint motion group demonstrated the greatest immediate increase in passive ROM (8°, p < .001) than the non-motion group (5°, p < .001). For PPT, the active joint motion group demonstrated the greatest immediate increase (180 kPa, p < .001) followed by the non-motion group (133 kPa, p < .001). Between group comparisons revealed a significance between groups for passive knee ROM (p < .001) and PPT (p < .001). A short session of foam rolling with active joint motion appears to have a greater effect on passive joint ROM and PPT than rolling without motion. These observed changes may be influenced by the agonistic muscle activity during active motion. This activity may modulate activity of the antagonist muscle through reciprocal inhibition and other neural pathways. Future research is needed to confirm these findings.


Evolution of an Efficient and Scalable Nine-Step (Longest Linear Sequence) Synthesis of Zincophorin Methyl Ester.
Because of both their synthetically challenging and stereochemically complex structures and their wide range of often clinically relevant biological activities, nonaromatic polyketide natural products have for decades attracted an enormous amount of attention from synthetic chemists and played an important role in the development of modern asymmetric synthesis. Often, such compounds are not available in quantity from natural sources, rendering analogue synthesis and drug development efforts extremely resource-intensive and time-consuming. In this arena, the quest for ever more step-economical and efficient methods and strategies, useful and important goals in their own right, takes on added importance, and the most useful syntheses will combine high levels of step-economy with efficiency and scalability. The nonaromatic polyketide natural product zincophorin methyl ester has attracted significant attention from synthetic chemists due primarily to the historically synthetically challenging C(8)-C(12) all-anti stereopentad. While great progress has been made in the development of new methodologies to more directly address this problem and as a result in the development of more highly step-economical syntheses, a synthesis that combines high levels of step economy with high levels of efficiency and scalability has remained elusive. To address this problem, we have devised a new synthesis of zincophorin methyl ester that proceeds in just nine steps in the longest linear sequence and proceeds in 10% overall yield. Additionally, the scalability and practicability of the route have been demonstrated by performing all of the steps on a meaningful scale. This synthesis thus represents by a significant margin the most step-economical, efficient, and practicable synthesis of this stereochemically complex natural product reported to date, and is well suited to facilitate the synthesis of analogues and medicinal chemistry development efforts in a time- and resource-efficient manner.


The role of diffusion tensor imaging in establishing the proximity of tumor borders to functional brain systems: implications for preoperative risk assessments and postoperative outcomes.
Diffusion Tensor Imaging (DTI) is a new MRI imaging technique sensitive to directional movements of water molecules, induced by tissue barriers. This provides a new form of contrast that allows the identification of functional white matter tracts within the brain, and has been proposed as a technique suitable for presurgical planning in brain tumor patients. Resection of primary brain tumors improves survival, functional performance, and the effectiveness of adjuvant therapies, provided that surgically-induced neurological deficits can be avoided. Diffusion Tensor Imaging (DTI) has the potential to establish spatial relationships between eloquent white matter and tumor borders, provide information essential to preoperative planning, and improve the accuracy of surgical risk assessments preoperatively. We present our experience in a series of 28 brain tumor patients where the integration of functional magnetic resonance imaging (fMRI) and DTI data was used to determine key anatomic spatial relationships preoperatively. Twice as many functional systems were localized to within 5 mm of tumor borders when DTI and fMRI were utilized for preoperative planning, compared to that afforded by fMRI alone. Our results show that the combined use of fMRI and DTI can provide a better estimation of the proximity of tumor borders to eloquent brain systems sub-serving language, speech, vision, motor and premotor functions. Additionally, a low regional complication rate (4%) observed in our series suggests that preoperative planning with these combined techniques may improve surgical outcomes compared to that previously reported in the literature. Larger studies specifically designed to establish the accuracy and predictive value of DTI in brain tumor patients are warranted to substantiate our preliminary observations.


Effectiveness of applying flipped learning to clinical nursing practicums for nursing students in Korea: A randomized controlled trial.
The purpose of this study was to develop flipped learning models for clinical practicums and compare their effectiveness regarding learner motivation toward learning, satisfaction, and confidence in performing core nursing skills among undergraduate nursing students in Korea. This study was a randomized clinical trial designed to compare the effectiveness of 2 flipped learning models. Data were collected for 3 days from October 21 to 23, 2015 before the clinical practicum was implemented and for 2 weeks from October 26 to December 18, 2015 during the practicum period. The confidence of the students in performing core nursing skills was likely to increase after they engaged in the clinical practicum in both study groups. However, while learner confidence and motivation were not affected by the type of flipped learning, learner satisfaction did differ between the 2 groups. The findings indicate that applying flipped learning allows students to conduct individualized learning with a diversity of clinical cases at their own level of understanding and at their own pace before they participate in real-world practicums.


Alcohol Outlet Clusters and Population Disparities.
Alcohol outlet clusters are an important social determinant of health in cities, but little is known about the populations exposed to them. If outlets cluster in neighborhoods comprised of specific racial/ethnic or economic groups, then they may function as a root cause of urban health disparities. This study used 2016 liquor license data (n = 1204) from Baltimore City, Maryland, and demographic data from the American Community Survey. We defined alcohol outlet clusters by combining SaTScan moving window methods and distances between outlets. We used multiple logistic regression to compare census block groups (CBGs) (n = 537) inside and outside of four types of outlet clusters: total, on-premise, off-premise, and LBD-7 (combined on-/off-premise). The most robust predictor of alcohol outlet cluster membership was a history of redlining, i.e., racially discriminatory lending policies. CBGs that were redlined had 7.32 times the odds of being in an off-premise cluster, 8.07 times the odds of being in an on-premise cluster, and 8.60 times the odds of being in a LBD-7 cluster. In addition, level of economic investment (marked by vacant properties) appears to be a key characteristic that separates CBGs in on- and off-premise outlet clusters. CBGs with racial/ethnic or socioeconomic advantage had higher odds of being in on-premise clusters and CBGs marked by disinvestment had higher odds of being in off-premise clusters. Off-premise clusters deserve closer examination from a policy perspective, to mitigate their potential role in creating and perpetuating social and health disparities. In addition to addressing redlining and disinvestment, the current negative effects of alcohol outlet clusters that have grown up in redlined and disinvested areas must be addressed if inequities in these neighborhoods are to be reversed.


A modified keyhole technique for correction of macroglossia.
The enlarged tongue, or macroglossia, may compromise vital function to the point that surgical correction is necessary. Although earlier procedures simply aimed at reducing tongue bulk, contemporary techniques attempt to decrease lingual dimension yet preserve critical neurosensory function. Still, modern approaches advise a broad variety of differing incisions and propose excision of various anterior, lateral, central, or circumferential lingual tissues. The keyhole technique allows direct excision of midline musculomucosal tissue along the tongue's length. With this central tongue-reduction procedure, significant lingual resection is possible and crucial tongue function and neurovascular structure are maintained. In this article, as a supplement to our video demonstration, we describe a modified keyhole technique for macroglossia correction.


Can DMCO Detect Visual Field Loss in Neurological Patients? A Secondary Validation Study.
Unrecognized visual field loss is caused by a range of blinding eye conditions as well as serious brain diseases. The commonest cause of asymptomatic visual field loss is glaucoma. No screening tools have been proven cost-effective. Damato Multifixation Campimetry Online (DMCO), an inexpensive online test, has been evaluated as a future cost-beneficial tool to detect glaucoma. To further validate DMCO, this study aimed to test DMCO in a preselected population with neurological visual field loss. The study design was an evaluation of a diagnostic test. Patients were included if they had undergone surgery for epilepsy during 2011-2014, resulting in visual field loss. They were examined with DMCO and results were compared with those obtained with the Humphrey Field Analyzer (30:2 SITA-Fast). DMCO sensitivity and specificity were estimated with 95% confidence intervals. The cohort comprised 40 patients (25 female and 15 male) with a mean age of 39 years (range 17-60 years). The mean visual acuity was >1.0 and all eyes had an intraocular pressure <21 mm Hg. Sensitivity and specificity of DMCO compared to the reference standard were 72.7 and 96.3%, respectively. DMCO detects moderate-to-severe homonymous quadrantanopia; it can be useful in settings where the current practice is confrontation visual field examination, and where standard conventional perimetry is not available.


Microdiscectomy with and without insertion of interspinous device for herniated disc at the L5-S1 level.
The role of interspinous devices (ISD) after lumbar herniated disc surgery for the prevention of postoperative back pain is controversial. The aim of this comparative prospective study was to determine outcomes in a selective cohort with L5-S1 disc herniation and degenerative disc changes after microdiscectomy with or without insertion of an ISD. One hundred and two consecutive patients underwent an L5-S1 microdiscectomy with or without implantation of an ISD. Group 1 consisted of 47 patients, with mild (n=22), moderate (n=14) or severe (n=11) degenerative disc changes who had microdiscectomy alone. Group 2 comprised 45 patients with similar types of disc changes who underwent microdiscectomy with an ISD implant. The Visual Analogue Scale (VAS) was used to grade low-back pain and postoperative clinical status was rated according to the modified MacNab criteria. Mean VAS score for low-back pain improved significantly at 1 year follow-up from 7.3 at baseline to 2.75 (p<0.001) in Group 1 and from 6.7 to 1.5 (p=0.001) in Group 2. VAS score at 1 year showed significant improvements in 21 Group 1 patients versus 30 Group 2 patients (p=0.001). Forty four percent of Group 1 patients and 80% of Group 2 patients showed improvement using the modified MacNab criteria. Patients in both groups reported significant improvement in sciatic pain and disability after microdiscectomy with or without an ISD implant. Patients with mild degenerative disc changes were more likely to achieve improvement of their low-back pain when treated with both microdiscectomy and ISD insertion.


Central serous chorioretinopathy after blunt trauma.
The authors report a case of a 46-year-old Hispanic male with central serous chorioretinopathy (CSC) following blunt trauma to the left eye. The patient presented with a complaint of throbbing headache and blurry vision in left eye. The patient was diagnosed with diabetes mellitus 1 year previous to the event. On examination, uncorrected visual acuity was 20/20 OD, 20/200 OS. No anisocoria or afferent pupillary defect was present. Intraocular pressure was normal. Subconjunctival haemorrhage and lid ecchymosis were present in OS and fundus examination showed serous macular detachment and central retinal pigment epithelium detachment, and no evidence of diabetic retinopathy. Optical coherence tomography OS showed subretinal fluid and fluorescein angiography demonstrated the typical 'smokestack' pattern of leakage into the subretinal space. The patient received observational therapy for 4 months and the CSC spontaneously resolved with visual acuity of 20/20 in left eye.


A rapid PCR-based DNA test for enterotoxic Bacillus cereus.
The occurrence of DNA sequences encoding the hemolysin HblA complex and Bacillus cereus enterotoxin BceT, which have recently been confirmed as enterotoxins, was studied in Bacillus spp. To amplify these DNA sequences, PCR primer systems for the B component of hblA and for bceT DNA sequences were developed. The results from the amplification of hblA sequences correlated well with results obtained with the B. cereus enterotoxin (diarrheal type) test kit (RPLA kit), but not with the results of the Bacillus diarrheal enterotoxin visual immunoassay (BDE kit). Except for two thermophilic strains, all strains that were positive in PCR amplification assays with the hblA primers were also positive when tested with the RPLA kit. The hblA DNA sequence was found in 33 strains, and these strains were closely related according to 16S rDNA-RFLP analysis, except B. pasteurii. In PCR amplifications with the bceT primers only the model strain gave a positive signal. It is concluded that screening of the hemolysin HblA complex by the PCR method allows faster detection of enterotoxin production than does testing with the RPLA enterotoxin kit.


CD20-Specific Immunoligands Engaging NKG2D Enhance γδ T Cell-Mediated Lysis of Lymphoma Cells.
Human γδ T cells are innate-like T cells which are able to kill a broad range of tumour cells and thus may have potential for cancer immunotherapy. The activating receptor natural killer group 2 member D (NKG2D) plays a key role in regulating immune responses driven by γδ T cells. Here, we explored whether recombinant immunoligands consisting of a CD20 single-chain fragment variable (scFv) linked to a NKG2D ligand, either MHC class I chain-related protein A (MICA) or UL16 binding protein 2 (ULBP2), could be employed to engage γδ T cells for tumour cell killing. The two immunoligands, designated MICA:7D8 and ULBP2:7D8, respectively, enhanced cytotoxicity of ex vivo-expanded γδ T cells against CD20-positive lymphoma cells. Both Vδ1 and Vδ2 γδ T cells were triggered by MICA:7D8 or ULBP2:7D8. Killing of CD20-negative tumour cells was not induced by the immunoligands, indicating their antigen specificity. MICA:7D8 and ULBP2:7D8 acted in a dose-dependent manner and induced cytotoxicity at nanomolar concentrations. Importantly, chronic lymphocytic leukaemia (CLL) cells isolated from patients were sensitized by the two immunoligands for γδ T cell cytotoxicity. In a combination approach, the immunoligands were combined with bromohydrin pyrophosphate (BrHPP), an agonist for Vδ2 γδ T cells, which further enhanced the efficacy in target cell killing. Thus, employing tumour-directed recombinant immunoligands which engage NKG2D may represent an attractive strategy to enhance antitumour cytotoxicity of γδ T cells.


Osteomyelitis and septic arthritis complicating hand injuries and infections: pathogenesis of roentgenographic abnormalities.
Osteomyelitis and pyarthrosis may complicate hand injuries and soft-tissue infections, resulting in characteristic radiographic findings. Evaluation of 78 patients revealed bone or joint abnormalities in 10% of individuals. Distinct pathways are available for spread of bacteria which become lodged in the soft tissues of the hand. Such routes include tendon sheaths, fascial planes and lymphatics. An understanding or pertinent anatomy allows the radiologist to predict the site and pattern of soft tissue, articular and osseous alterations.


Influence of Polarizability on the Structure, Dynamic Characteristics, and Ion-Transport Mechanisms in Polymeric Ionic Liquids.
We used atomistic simulations and compared the prediction of three different implementations of force fields, namely, the original full partial charge system, the scaled partial charge system, and the Drude oscillator polarizable force field and its effect on the structural and dynamic properties of a polymeric ionic liquid, poly(1-butyl-3-methyl-imidazolium hexafluorophosphate). We found that both the scaled and the polarizable force field models yield comparable predictions of structural and dynamic properties, although the scaled charge model artificially lowers the first-neighbor peak of the radial distribution function and therefore leads to a slight reduction in density. The full charge model was not accurate in its prediction of the dynamic properties but could reproduce the structural properties. With a refined analysis method for the ion-hopping mechanisms, we found that all three methods produce very similar conclusions, namely, that the mobile anion is associated with three cations from two distinct polymer chains and that the fractions of inter- and intramolecular hopping events are comparable. Our results demonstrate that the scaled charge force fields provide a computationally efficient means to capture polarizability effects on both the structural and dynamic properties of polymeric ionic liquid systems.


Entamoeba histolytica: a snapshot of current research and methods for genetic analysis.
Entamoeba histolytica represents one of the leading causes of parasitic death worldwide. Although identified as the causative agent of amebiasis since 1875, the molecular mechanisms by which the parasite causes disease are still not fully understood. Studying Entamoeba reveals insights into a eukaryotic cell that differs in many ways from better-studied model organisms. Thus, much can be learned from this protozoan parasite on evolution, cell biology, and RNA biology. In this review we discuss selected research highlights in Entamoeba research and focus on the development of molecular biological techniques to study this pathogen. We end by highlighting some of the many questions that remain to be answered in order to fully understand this important human pathogen.


Feasibility of measuring 5-fluorouracil catabolic potential by oral loading.
The efficacy of 5-fluorouracil (5-FU) treatment and the incidence of adverse events differ among patients and depend to some extent on individual variations in drug catabolism. This feasibility study aimed to determine the optimum conditions for a 5-FU oral load test, which would allow the simple evaluation of individual differences in 5-FU catabolism. Patients with colon cancer were given oral 5-FU (200 mg/day) for 3 days (n = 36) or a single 100 mg dose (n = 14). Serum concentrations of uracil, dihydrouracil, 5-FU and 5-fluoro-5,6-dihydrouracil were measured before and after 5-FU administration. The results suggested that a decline in 5-FU metabolism was associated with continuous administration and increasing age. We conclude that a continuous load of 5-FU is necessary in order to predict the efficacy and side-effects of the drug. The 3-day regimen, with its ease of administration, merits further study to assess its possible clinical application.


A new cis-acting motif is required for the axonal SMN-dependent Anxa2 mRNA localization.
Spinal muscular atrophy (SMA) is caused by mutations and/or deletions of the survival motor neuron gene (SMN1). Besides its function in the biogenesis of spliceosomal snRNPs, SMN might possess a motor neuron specific role and could function in the transport of axonal mRNAs and in the modulation of local protein translation. Accordingly, SMN colocalizes with axonal mRNAs of differentiated NSC-34 motor neuron-like cells. We recently showed that SMN depletion gives rise to a decrease in the axonal transport of the mRNAs encoding Annexin A2 (Anxa2). In this work, we have characterized the structural features of the Anxa2 mRNA required for its axonal targeting by SMN. We found that a G-rich motif located near the 3'UTR is essential for axonal localization of the Anxa2 transcript. We also show that mutations in the motif sequence abolish targeting of Anxa2 reporter mRNAs in axon-like structures of differentiated NSC-34 cells. Finally, localization of both wild-type and mutated Anxa2 reporters is restricted to the cell body in SMN-depleted cells. Altogether, our studies show that this G-motif represents a novel and essential determinant for axonal localization of the Anxa2 mRNA mediated by the SMN complex.


Effect of perioperative glucocorticoid administration on postoperative complications following esophagectomy: A meta-analysis.
Perioperative corticosteroid administration is a controversial therapy for improving the short-term prognosis following surgery. The objective of the current meta-analysis was to evaluate the effects of the perioperative use of corticosteroids during esophagectomy for esophageal carcinoma. A comprehensive study was performed using references selected from the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE (Ovid databases), EMBASE and three Chinese databases (Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure and VIP Database for Chinese Technical Periodicals). Eligible studies were restricted to randomized clinical trials that reported data from patients undergoing esophagectomy. In addition, treated groups of patients received perioperative corticosteroid administration and control groups received a placebo infusion, such as saline water. The studies evaluated the incidence of postoperative complications and the variation of inflammatory mediators. All extracted data underwent meta-analysis using Review Manager 5.1 software. Only six studies were eligible for selection. The following parameters were found to be reduced following the use of methylprednisolone: Interleukin (IL)-6 immediately following surgery and on postoperative days (PODs) 1 and 3; IL-8 immediately following surgery; and PaO2/FiO2 on POD 3. Moreover, organ failure, cardiovascular complications and pulmonary morbidity were all reduced in patients with corticosteroid usage. Certain factors showed no significant differences between the treated and control groups, including IL-8 on POD 1, IL-6 prior to surgery and on POD 5, PaO2/FiO2 following surgery, mortality, anastomotic leakage, severe infection and renal and hepatic failure. Prophylactic administration of methylprednisolone during the perioperative period may reduce the incidence of specific types of postoperative complications and inhibit the postoperative inflammatory reaction. Additional randomized controlled trials must be performed.


Training of emergency dispatch-center personnel in Sweden.
The ability to recognize symptoms, to make priority decisions, to dispatch suitable ambulance transport and inform the crews, and finally, to initiate first aid via the caller is essential for optimum care of severely injured or ill patients outside the hospital. In Sweden, a special job-related course trains dispatch-center personnel to think in terms of symptoms and evolution of the victim's status, and to assess the level of seriousness.


[Specifics of activation of cortex by stimulation of support receptors in healthy subjects and in patients with lesions of CNS].
Results of basic studies in space medicine revealed the mechanism of motor disorders and the importance of support input in regulation of the tone and posture system of the mammals. Progress in functional magnetic resonance tomography (fMRT) enabled in vivo estimation of activity of various parts of the brain during stimulation of support afferent pathways. The goal of our study was to detect specific activation of the cortex during stimulation of support input in healthy subjects and in patients with lesions of CNS. The study included 19 healthy volunteers (mean age of 38 ± 15, 13 years) and 23 patients with cortical-subcortical ischemic stroke (mean age 53 ± 9.07); all subjects underwent fMRT. During scanning of each subject, support areas of the foot soles were stimulated to imitate slow walking using the block design. In healthy volunteers, primary somatosensory cortex, premotor and dorsolateral cortex, and insula were significantly activated (corrected <0.05 at cluster level). In patients with stroke, pattern of activation of the supraspinal systems of locomotion control clearly depended on the stage of the disease. In patients with cortical-subcortical stroke undergoing motility rehabilitation, the sensomotor locomotion module was predominantly activated as the contralateral pattern.


Feedback-Driven Sensory Mapping Adaptation for Robust Speech Activity Detection.
Parsing natural acoustic scenes using computational methodologies poses many challenges. Given the rich and complex nature of the acoustic environment, data mismatch between train and test conditions is a major hurdle in data-driven audio processing systems. In contrast, the brain exhibits a remarkable ability at segmenting acoustic scenes with relative ease. When tackling challenging listening conditions that are often faced in everyday life, the biological system relies on a number of principles that allow it to effortlessly parse its rich soundscape. In the current study, we leverage a key principle employed by the auditory system: its ability to adapt the neural representation of its sensory input in a high-dimensional space. We propose a framework that mimics this process in a computational model for robust speech activity detection. The system employs a 2-D Gabor filter bank whose parameters are retuned offline to improve the separability between the feature representation of speech and nonspeech sounds. This retuning process, driven by feedback from statistical models of speech and nonspeech classes, attempts to minimize the misclassification risk of mismatched data, with respect to the original statistical models. We hypothesize that this risk minimization procedure results in an emphasis of unique speech and nonspeech modulations in the high-dimensional space. We show that such an adapted system is indeed robust to other novel conditions, with a marked reduction in equal error rates for a variety of databases with additive and convolutive noise distortions. We discuss the lessons learned from biology with regard to adapting to an ever-changing acoustic environment and the impact on building truly intelligent audio processing systems.


Saliva is Comparable to Nasopharyngeal Swabs for Molecular Detection of SARS-CoV-2.
The continued need for molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the potential for self-collected saliva as an alternative to nasopharyngeal (NP) swabs for sample acquisition led us to compare saliva to NP swabs in an outpatient setting without restrictions to avoid food, drink, smoking, or tooth-brushing. A total of 385 pairs of NP and saliva specimens were obtained, the majority from individuals presenting for initial evaluation, and were tested on two high-sensitivity reverse transcriptase PCR (RT-PCR) platforms, the Abbott m2000 and Abbott Alinity m (both with limits of detection [LoD] of 100 copies of viral RNA/ml). Concordance between saliva and NP swabs was excellent overall (Cohen's κ = 0.93) for both initial and follow-up testing, for both platforms, and for specimens treated with guanidinium transport medium as preservative as well as for untreated saliva (κ = 0.88 to 0.95). Viral loads were on average 16× higher in NP specimens than saliva specimens, suggesting that only the relatively small fraction of outpatients (∼8% in this study) who present with very low viral loads (<1,600 copies/ml from NP swabs) would be missed by testing saliva instead of NP swabs when using sensitive testing platforms. Special attention was necessary to ensure leak-resistant specimen collection and transport. The advantages of self-collection of saliva, without behavioral restrictions, will likely outweigh a minor potential decrease in clinical sensitivity in individuals less likely to pose an infectious risk to others for many real-world scenarios, especially for initial testing. IMPORTANCE In general, the most accurate COVID-19 testing is hands-on and uncomfortable, requiring trained staff and a "brain-tickling" nasopharyngeal swab. Saliva would be much easier on both fronts, since patients could collect it themselves, and it is after all just spit. However, despite much interest, it remains unclear how well saliva performs in real-world settings when just using it in place of an NP swab without elaborate or cumbersome restrictions about not eating/drinking before testing, etc. Also, almost all studies of COVID-19 testing, whether of NP swabs, saliva, or otherwise, have been restricted to reporting results in the abstruse units of "CT values," which only mean something in the context of a specific assay and testing platform. Here, we compared saliva versus NP swabs in a real-world setting without restriction and report all results in natural units-the amount of virus being shed-showing that saliva is essentially just as good as NP swabs.


A competitive ELISA for the anti-intercellular adhesion molecule-1 (anti-ICAM-1) binding activity of monoclonal antibody R6.5 in serum.
A competitive ELISA was developed to measure serum concentrations of immunoreactive R6.5, a mouse IgG2a monoclonal antibody which binds to and inhibits the interactions of human intercellular adhesion molecule-1 with glycoproteins of the CD18 complex and with rhinoviruses. The assay design permitted quantitative measurement of the functional activity of the antibody in serum. The working range of the assay was from 2.15 to 215 ng ml-1, and intra-assay and inter-assay relative standard deviations averaged 13 and 20%, respectively. Serum caused interferences with the assay when spiked in vitro, but authentic serum samples obtained from intravenously dosed animals did not exhibit these interferences. Characteristics of the assay, as well as results of a pharmacokinetic study in rabbits, are presented.


Oxygen metabolites from lavage and interstitial lung cells after inhalation of endotoxin in guinea pigs.
Airborne endotoxins play a role in a variety of occupational diseases such as byssinosis and humidifier's disease and are associated with pulmonary and systemic symptoms. An excess generation of oxygen free radicals (including superoxide anion, O2-) by inflammatory cells has been suggested in endotoxemia. We have studied the release of superoxide from guinea-pig lung lavage and interstitial cells and blood monocytes (BMs) at different times after an acute inhalation exposure to bacterial endotoxin. O2- generation was measured by the O2- dismutase-inhibitable reduction of ferricytochrome c, after stimulation with phorbol-myristate-acetate (PMA) or opsonized zymosan (OZ). After endotoxin exposure, the spontaneous release of O2- remained unchanged for the three cell types. From 4 h after exposure until 48 h afterwards, lung lavage cells produced more O2- after PMA or OZ stimulation than did cells from unexposed guinea pigs. The pattern of O2- generation by interstitial cells followed that of lung lavage macrophages. O2- production remained unchanged in BMs at all times. These results suggest that endotoxin inhalation induced a priming of lavage and interstitial cells, mainly macrophages, associated with an increase in O2- production. As O2- production by BMs remained unchanged, this cell is unlikely to be responsible for the systemic symptoms seen after endotoxin inhalation.


Selective cysteine-->serine replacements in p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens allow the unambiguous assignment of Cys211 as the site of modification by spin-labeled p-chloromercuribenzoate.
p-Hydroxybenzoate hydroxylase from Pseudomonas fluorescens contains five sulfhydryl groups per subunit. Cysteine-->serine replacements show that the thiols are not essential for catalysis. The increased dissociation constant for FAD in mutant Cys158Ser suggests that Cys158 is important for the solvation of the pyrophosphate moiety of the prosthetic group. Wild-type p-hydroxybenzoate hydroxylase is rapidly inactivated by mercurial compounds. Inactivation by a spin-labeled derivative of p-chloromercuribenzoate is fully abolished in mutant Cys211Ser. Incorporation of the spin label in the other Cys-->Ser mutants strongly impairs substrate binding without affecting the catalytic properties of the FAD. The results are discussed with respect to previous tentative assignments from chemical modification studies and in light of the 3-D structure of the enzyme-substrate complex.


Silencing long non-coding RNA SNHG6 restrains proliferation, migration and invasion of Wilms' tumour cell lines by regulating miR-15a.
Wilms' tumour (WT) is a frequent primary malignant tumour of urinary system in children. LncRNAs small nucleolar RNA host gene 6 (SNHG6) modulates kinds of biological procedures of cancer cells. Our research is to explore the effect and associated regulatory mechanism of SNHG6 in WT. CCK8 assays and bromodeoxyuridine were used to determine cell viability and cell proliferation, respectively. Flow cytometric analysis was performed to measure cell apoptosis rate. Cell mobility was tested through transwell and migration assays. Western blotting was employed to test the expression of proteins related to cell proliferation, cell apoptosis and signal pathways. In the results, overexpression of SNHG6 was found in WT tissues. The knockdown of SNHG6 suppressed cell proliferation, migration and incursion, but promoted apoptosis. Further study found that the knockdown of SNHG6 elevated the expression of miR-15a. Then, the combination of miR-15a inhibitor abolished the inhibiting effect of si-SNHG6 on WT progression. We also found that the TAK1/JNK and Wnt/β-catenin signal pathways were inactivated by the knockdown of SNHG6 through elevating the expression of miR-15a. In summary, SNHG6 is an oncogene of WT development by targeting miR-15a.


Determinants of HIV/AIDS-related information needs and media use: beyond individual-level factors.
Despite the centrality of information and communication in the fight against HIV/AIDS, little research has investigated the factors associated with HIV/AIDS-related information needs and media use in hard-hit Sub-Saharan Africa. This study explored individual-level and socioecological determinants among urban and rural residents in northwest Ethiopia. Urbanity versus rurality, education, direct experience with HIV/AIDS, perceived salience of HIV/AIDS-related information, and personal health concern were tested as predictors. Regression analyses showed that urbanity versus rurality and education are the major determinants of HIV/AIDS-related information needs and media use. Being urbanite and educated were associated with high concern about and information needs on HIV/AIDS and HIV/AIDS-related mass media use. Moreover, urbanity versus rurality and education significantly predicted preferences for specific types of HIV/AIDS-related information. While rurality and low education were associated with a preference for basic HIV transmission and prevention information, urbanity was associated with a preference for information on HIV/AIDS-related care and support. In most cases, urbanity versus rurality emerged as a substantial predictor and also significantly moderated the effects of other variables. Given the evolving nature of the pandemic and its expansion to rural areas, ruralites' low information needs and media use deserve due attention. Equally, communication interventions targeting urban contexts need to move beyond providing only the ABCs of HIV transmission and prevention and should attend to urbanites' progressive information needs, which seem to have now become more on care and support so as to live and deal with the pandemic.


Three-dimensional bioprinting in ophthalmic care.
Three-dimensional (3D) bioprinting is widely used in ophthalmic clinic, including in diagnosis, surgery, prosthetics, medications, drug development and delivery, and medical education. Articles published in 2011-2022 into bioinks, printing technologies, and bioprinting applications in ophthalmology were reviewed and the strengths and limitations of bioprinting in ophthalmology highlighted. The review highlighted the trade-offs of printing technologies and bioinks in respect to, among others, material type cost, throughput, gelation technique, cell density, cell viability, resolution, and printing speed. There is already widespread ophthalmological application of bioprinting outside clinical settings, including in educational modelling, retinal imaging/visualization techniques and drug design/testing. In clinical settings, bioprinting has already found application in pre-operatory planning. Even so, the findings showed that even with its immense promise, actual translation to clinical applications remains distant, but relatively closer for the corneal (except stromal) tissues, epithelium, endothelium, and conjunctiva, than it was for the retina. This review similarly reflected on the critical on the technical, practical, ethical, and cost barrier to rapid progress of bioprinting in ophthalmology, including accessibility to the most sophisticated bioprinting technologies, choice, and suitability of bioinks, tissue viability and storage conditions. The extant research is encouraging, but more work is clearly required for the push towards clinical translation of research.


Bioacoustics of human whistled languages: an alternative approach to the cognitive processes of language.
Whistled languages are a valuable heritage of human culture. This paper gives a first survey about a new multidisciplinary approach to these languages. Previous studies on whistled equivalents of languages have already documented that they can provide significant information about the role of rhythm and melody in language. To substantiate this, most whistles are represented by modulations of frequency, centered around 2000 Hz (+/- 1000 Hz) and often reach a loudness of about 130 dB (measured at 1m from the source). Their transmission range can reach up to 10 km (as verified in La Gomera, Canary Island), and the messages can remain understandable, even if the signal is deteriorated. In some cultures the use of whistled language is associated with some "talking musical instruments" (e.g. flutes, guitars, harps, gongs, drums, khens). Finally, whistles as a means of conveying information have some analogues in the animal kingdom (e.g. some birds, cetaceans, primates), providing opportunities to compare the acoustic characteristics of the respective signals. With such properties as a reference, the project reported here has two major tasks: to further elucidate the many facets of whistled language and, above all, help to immediately stop the process of its gradual disappearance.


Gene therapy in epilepsy: the focus on NPY.
Gene therapy represents an innovative and promising alternative for the treatment of epileptic patients who are resistant to conventional antiepileptic drugs. Among the various approaches for the application of gene therapy in the treatment of CNS disorders, recombinant viral vectors have been most widely used so far. Several gene targets could be used to correct the compromized balance between inhibitory and excitatory transmission in epilepsy. Transduction of neuropeptide genes such as galanin and neuropeptide Y (NPY) in specific brain areas in experimental models of seizures resulted in significant anticonvulsant effects. In particular, the long-lasting NPY over-expression obtained in the rat hippocampus using intracerebral application of recombinant adeno-associated viral (AAV) vectors reduced the generalization of seizures from their site of onset, delayed acquisition of fully kindled seizures and afforded neuroprotection. These results establish a proof-of-principle for the applicability of AAV-NPY vectors for the inhibition of seizures in epilepsy. Additional investigations are required to demonstrate a therapeutic role of gene therapy in chronic models of seizures and to address in more detail safety concerns and possible side-effects.


Correlations of GDF-15 with sST2, MMPs, and worsening functional capacity in idiopathic dilated cardiomyopathy: Can we gain new insights into the pathophysiology?
Growth and differentiation factor-15 (GDF-15) has been implicated in fibrosis, inflammation, and ventricular remodeling. The role of GDF-15 in the regulation of cardiac remodeling in idiopathic dilated cardiomyopathy (DCM) remains poorly defined. This study attempts to analyze the molecular interactions between GDF-15 and markers of fibrosis as well as its positive correlations with worsening functional capacity. The study population consisted of 24 DCM patients and 8 control subjects. All DCM patients had normal coronary angiographic studies. Plasma levels of GDF-15, matrix metalloproteinase-2 (MMP2), MMP3, MMP9, tissue inhibitor of MMP 1 (TIMP1), and soluble suppression of tumorigenicity-2 protein (sST2) were determined by enzyme-linked immunosorbent assays. Brain Natriuretic Peptide (BNP) was measured as per core laboratory protocol assay at Scott and White Memorial Hospital core laboratory. Correlation analysis was performed between GDF-15 and each of the MMPs-MMP2, MMP3, MMP9, and TIMP as well as New York Heart Association (NYHA) class and echocardiographic parameters (left ventricular ejection fraction (LVEF) and left ventricular internal dimension in diastole (LVIDd)). LVEF and LVIDd were obtained by two-dimensional echocardiography. The protocol was approved by Scott and White Memorial Hospital Institutional Review Board (S&W IRB). Correlation analysis of control versus all DCM patients showed a strong correlation of GDF-15 with TIMP1 (r = 0.83, p < 0.0001) and weaker correlation with MMP3 (r = 0.41, p = 0.011) and MMP2 (r = 0.47, p = 0.003). MMP9 showed poor correlation with GDF-15 (r = 0.3036, p = 0.046). GDF-15 correlated negatively with MMP2/TIMP1 ratio (r = -0.47, p = 0.006). sST2 correlated strongly with GDF-15 (r = 0.7, p < 0.0001). GDF-15 correlated negatively with LVEF (r = -0.49, p = 0.004) and positively with LVIDd (r = 0.58, p = 0.0006). GDF-15 showed significant positive correlation with NYHA functional class (r = 0.71, p < 0.00001) and BNP (r = 0.86, p < 0.00001). Significant associations of GDF-15 with MMPs, sST2, LVIDd, LVEF, and NYHA class reported here for the first time in nonischemic dilated hearts may open up new avenues of investigations to better understand molecular mechanisms controlling cardiac remodeling. This study is limited by its small size and needs validation in larger populations.


Syntheses, antibacterial, cytotoxic and antifungal effects of new 3-carboxy-l-phenacylpyridinium salts.
Thirteen pyridine-3-carboxylic acid salt derivatives with various substituted phenacyl residues were prepared and their cytotoxicity, antibacterial and antifungal activities tested. Compounds 5 and 11 proved to be active in the brine shrimp bioassay, compounds 7, 9-12 and 14 showed promising antibacterial activities, whereas none of the compounds tested against 15 fungal cultures proved to be active. Extensive spectroscopic techniques were employed to confirm the structure of the synthetic products.


Implications of Resveratrol on Glucose Uptake and Metabolism.
Resveratrol-a polyphenol of natural origin-has been the object of massive research in the past decade because of its potential use in cancer therapy. However, resveratrol has shown an extensive range of cellular targets and effects, which hinders the use of the molecule for medical applications including cancer and type 2 diabetes. Here, we review the latest advances in understanding how resveratrol modulates glucose uptake, regulates cellular metabolism, and how this may be useful to improve current therapies. We discuss challenges and findings regarding the inhibition of glucose uptake by resveratrol and other polyphenols of similar chemical structure. We review alternatives that can be exploited to improve cancer therapies, including the use of other polyphenols, or the combination of resveratrol with other molecules and their impact on glucose homeostasis in cancer and diabetes.


Modeling the charge distribution at metal sites in proteins for molecular dynamics simulations.
Almost half of the proteome of living organisms is constituted of metalloproteins. Unfortunately, the ability of the current generation of molecular dynamics pairwise-additive forcefields to properly describe metal pockets is severely lacking due to the intrinsic difficulty of handling polarization and charge transfer contributions. In order to improve the description of metalloproteins, a simple reparameterization strategy is proposed herein that does not involve artificial constraints. Specifically, a non-bonded quantum mechanical-based model is used to capture the mean polarization and charge transfer contributions to the interatomic forces within the metal site. The present approach is demonstrated to provide enough accuracy to maintain the integrity of the metal pocket for a variety of metalloproteins during extended (multi-nanosecond) molecular dynamics simulations. The method enables the sampling of small conformational changes and the relaxation of local frustrations in NMR structures.


A simple and rapid in vitro test for large-scale screening of fungal endophytes from drought-adapted Australian wild plants for conferring water deprivation tolerance and growth promotion in Nicotiana benthamiana seedlings.
Some fungal endophytes confer novel phenotypes and enhance existing ones in plants, including tolerance to water deprivation stress. A range of fungal endophytes was isolated from wild Nicotiana plants growing in arid parts of northern Australia. These were screened for ability to enhance water deprivation stress tolerance by inoculating seedlings of the model plant N. benthamiana in two in vitro tests. Sixty-eight endophyte isolates were co-cultivated with N. benthamiana seedlings on either damp filter paper or on agar medium before being subjected to water deprivation. Seventeen isolates were selected for further testing under water deprivation conditions in a sand-based test in a glasshouse. Only two fungal isolates, Cladosporium cladosporioides (E-162) and an unknown fungus (E-284), significantly enhanced seedling tolerance to moisture deprivation consistently in both in vitro and sand-based tests. Although a strongly significant correlation was observed between any two screening methods, the result of filter paper test was more strongly reflected (r = 0.757, p < 0.001) in results of the glasshouse test, indicating its relative suitability over the agar-based test. In another experiment, the same 17 isolates carried forward to the sand-based test used in the glasshouse screening test were inoculated to N. benthamiana plants in pots in a nutrient-limiting environment to test their influence on growth promotion. Isolates related to C. cladosporioides, Fusarium equiseti, and Thozetella sp. promoted seedling growth by increasing shoot length and biomass. The fungal isolate E-162 (C. cladosporioides) significantly enhanced moisture deprivation tolerance as well as promoted seedling growth.


"Ecstasy" to addiction: Mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA.
This study aimed to address the mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA commonly reported in "Ecstasy" formulations: methylone, butylone, and pentylone. Whole-cell patch clamp techniques were used to assess the mechanism of each compound at the dopamine and serotonin transporters. Separate groups of rats were trained to discriminate methamphetamine, DOM, or MDMA from vehicle. Substitution studies were performed in each group and antagonism studies with SCH23390 were performed against each compound that produced substitution. Self-administration of each compound was evaluated under a progressive ratio schedule of reinforcement. Each compound produced an inward current at the serotonin transporter, but little or no current at the dopamine transporter. Each of the test compounds substituted fully for the discriminative stimulus effects of methamphetamine, methylone and butylone substituted partially for DOM and fully for MDMA, whereas pentylone failed to substitute for DOM and substituted only partially for MDMA. SCH23390 fully and dose-dependently attenuated methamphetamine-appropriate responding produced by each test compound, but was least potent against pentylone. MDMA-appropriate responding was minimally affected by SCH23390. Each test compound was robustly self-administered with pentylone producing the greatest self-administration at the doses tested. Given the prevalence of synthetic cathinones in "Ecstasy" formulations, these data indicate that adulterated "Ecstasy" formulations may drive more compulsive drug use than those containing only MDMA.


Low serum triglyceride levels as predictors of cardiac death in heart failure patients.
Understanding the influence of sex differences on predictors of cardiac mortality rates in chronic heart failure might enable us to lengthen lifetimes and to improve lives. This study describes the influence of sex on cardiovascular mortality rates among chronic heart failure patients. From January 2003 through December 2009, we evaluated 637 consecutive patients (409 men and 228 women) with chronic heart failure, who ranged in age from 18 through 94 years (mean age, 64 ± 13 yr) and ranged in New York Heart Association (NYHA) functional class from II through IV. The mean follow-up period was 38 ± 15 months, the mean age was 64 ± 13 years, and the mean left ventricular ejection fraction was 0.27 ±0.11. By the end of the study, both sexes had similar cardiovascular mortality rates (36% men vs 37% women, P=0.559). In Cox regression analysis, NYHA functional class, triglyceride level, and history of coronary artery disease were independent predictors of cardiovascular death for women with chronic heart failure. For men with chronic heart failure, the patient's age, ejection fraction, and sodium level were independent predictors of cardiovascular death. In a modern tertiary referral heart failure clinic, decreased triglyceride levels were, upon univariate analysis, predictors of poor outcomes for both men and women. However, upon Cox regression analysis, reduced triglyceride levels were independent predictors of cardiac death only in women.


Probability of the moiré effect in barrier and lenticular autostereoscopic 3D displays.
The probability of the moiré effect in LCD displays is estimated as a function of angle based on the experimental data; a theoretical function (node spacing) is proposed basing on the distance between nodes. Both functions are close to each other. The connection between the probability of the moiré effect and the Thomae's function is also found. The function proposed in this paper can be used in the minimization of the moiré effect in visual displays, especially in autostereoscopic 3D displays.


Evaluation of a physical activity program for pathological gamblers in treatment.
It has been demonstrated that craving for gambling is associated with anxiety and depression in pathological gamblers. Exercise has been shown to reduce anxiety and depression, as well as positively influence abstinence rates in individuals with substance use disorders. In this study, we examined the impact of a physical activity program in 33 pathological gamblers. We also analyzed the association between craving and plasmatic levels of stress hormones (adrenocorticotropic hormone, cortisol, and prolactin). The program involved eight 50-min sessions. Craving was assessed 24 h before, immediately before, and immediately after each session, as well as on a weekly basis. Before and after the program, we evaluated gambling behavior, depressive symptoms, anxiety, and plasma levels of stress hormones. We identified a significant reduction in craving following each session and at the end of the program. There was improvement in anxiety, depressive symptoms, and gambling behavior. The post-session reduction in craving was accompanied by post-program reductions in craving and anxiety but not by a post-program reduction in depressive symptoms. The craving reduction was associated with a variation in prolactin levels but not with variations in levels of cortisol or adrenocorticotropic hormone.


[A case of liver metastasis from esophageal cancer treated with stereotactic body radiation therapy].
A 70-year-old woman was diagnosed as having advanced lower thoracic esophageal cancer with abdominal lymph node metastases(T3N1M0, Stage III). After administering 2 courses of neoadjuvant chemotherapy with 5-fluorouracil(5- FU)( 800 mg/m2)and cisplatin(80 mg/m2), we performed curative surgery with D2 lymph node dissection. The patient could not receive adjuvant chemotherapy because of her poor performance status. After curative surgery, liver metastasis appeared in segment 8. The liver metastasis(S8)was treated with stereotactic body radiation therapy(SBRT)( 60 Gy/3 Fr). After SBRT, we administered systemic chemotherapy with docetaxel and nedaplatin as second-line chemotherapy. The patient had no recurrence for 12 months after SBRT. SBRT exhibited an excellent local therapeutic effect without any serious complications, suggesting that it is an effective treatment for liver metastasis from esophageal cancer.


Pd/Cu-Catalyzed tandem head-to-tail dimerization/cycloisomerization of terminal ynamides for the synthesis of 5-vinyloxazolones.
An attractive and novel methodology involving Pd/Cu-catalyzed tandem head-to-tail dimerization/cycloisomerization of terminal ynamides for the synthesis of 3,5-disubstituted oxazolones was developed. Under Pd(PPh3)2Cl2/CuI cooperative catalyzed reaction conditions, it provided efficient access to 5-vinyloxazolones with exceptional functional group tolerance and good chemoselectivity. The control experiments demonstrated that Pd(PPh3)2Cl2 serves a key role in the dimerization of terminal ynamides and shows low catalytic activity in the intramolecular cyclization. Moreover, the hetero-Diels-Alder reaction of product 5-vinyloxazolones was also described, which provided polycyclic oxazolones in good yield.


Clinical and Microbiological Characteristics of Candidemia Cases in Saudi Arabia.
Candidemia and antifungal resistance are major healthcare challenges. The aim of this study is to describe the frequency of candidemia cases, distribution of Candida spp., and the associated risk factors for mortality in an academic institution in Saudi Arabia over an 18-month period. We also evaluated the susceptibility patterns of Candida blood isolates. Candidemia cases were collected from King Fahad Hospital of the University over the period between July 1st, 2020 through December 31st, 2021. They were prospectively reviewed for the preceding risk factors and antifungal (AF) susceptibility, testing results to fluconazole (FL), voriconazole (VO), itraconazole (IT), posaconazole (PO), caspofungin (CASP), anidulafungin (AND), micafungin (MYC), flucytosine (FLC) and amphotericin B (AMPB) using a broth microdilution kit (Sensititre™ YeastOne). A total of 48 candidemia isolates were included that were isolated from 43 patients. The median age of cases was 62 ± 23.3 years (60.4% males and 83% ICU patients). Independent risk factors for mortality at 30 days in candidemia patients were age, COVID-19 co-infection, and use of tocilizumab. The most commonly isolated species were C. glabrata and C. parapsilosis (22.9% each) followed by C. albicans (18.75%). AF resistance for ≥1 antifungal was detected in 39.3% of 33 cases tested, with no cross-resistance identified. Resistance rates for each AF were as follows: FL (18%), VO (6%), IT (6%), PO (9%) and AMPB (3%). No resistance was seen for echinocandins apart from one C. krusei strain showing an intermediate result for CASP. The study showed an overall high rate of non-albicans Candida, with the predominance of C. parapsilosis and C. glabrata, representing a therapeutic challenge. AF resistance rate was high which emphasizes the importance of continuing surveillance and providing accurate and reliable tools in the laboratories for rapid speciation and susceptibility testing.


[Equations for segregation frequencies determined by Weinberg's generalized method in a model of a single autosomal 2-allelic locus with incomplete penetrance].
Equations are proposed for segregation frequencies determined by generalized Weinberg's method (SFw). The equations give an expression for SFw in terms of basic parameters of a single autosomal two-allele locus model with incomplete penetrance (SAL-2 model), namely, in terms of the frequency of one of the alleles and the penetrances of three genotypes (p, II2, II1, II0). The equations proposed are intended to be included into the system of equations to find the basic parameters of the SAL-2 model.


Comparative study of MR mTI-ASL and DSC-PWI in evaluating cerebral hemodynamics of patients with Moyamoya disease.
The aim of this study was to explore the correlation between multi-inversion time arterial spin labeling (mTI-ASL) and dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI) in assessment of hemodynamics of patients with Moyamoya disease (MMD).In this study, 24 MMD patients and 21 healthy subjects were enrolled between June 2017 and December 2017. The images of mTI-ASL and DSC-PWI in the week before revascularization surgery were retrospectively analyzed. The parameters of cerebral blood flow (CBF), time to peak (TTP), and bolus arrival time (BAT) were measured in regions of interest (ROIs) of lateral middle cerebral artery (MCA) territories, basal ganglia (BG), and cerebellum, and relative perfusion parameters (rCBF-ASL, rBAT-ASL, rCBF-DSC, and rTTP-DSC) were calculated by dividing by cerebellum value. One-way analysis of variance and Student-Newman-Keuls tests were performed to compare rCBF-ASL and rCBF-DSC in the MMD group and the control group. Unpaired t test was used to compare rBAT-ASL and rTTP-DSC in the MMD group and the control group. And we assessed the correlation between rCBF-ASL and rCBF-DSC and between rBAT-ASL and rTTP-DSC using Pearson correlation analysis.All the relative parameters were significantly different between the MMD group and the control group (all P<.05). Meanwhile, there was significant difference between rCBF-ASL and rCBF-DSC (P<.05), and there was strong correlation between rCBF-ASL and rCBF-DSC (r = 0.839, P<.001), and moderate correlation between rBAT-ASL and rTTP-DSC (r = 0.519, P<.001).Both mTI-ASL and DSC-PWI could be used to assess perfusion state in MMD patients before revascularization surgery effectively. As a noninvasive imaging technique, mTI-ASL could provide perfusion parameters without contrast medium injection, and the results were quite correlative with DSC-PWI.


Sumoylation of CCAAT-enhancer-binding protein α inhibits lung differentiation in Bronchopulmonary Dysplasia model rats.
Bronchopulmonary dysplasia (BPD) is a major cause of mortality and morbidity in premature infants, characterized by alveolar simplification, surfactant deficiency, and respiratory distress. In the present study, we have investigated the functional roles of sumoylated CCAAT/enhancer binding protein alpha (C/EBPα) in the BPD rat model. A significant increase in small ubiquitin-like modifier 1 (SUMO1) and sumoylated C/EBPα protein levels were observed in BPD rats, and the levels of the sumoylated C/EBPα were associated with the pulmonary surfactant proteins (SPs). In order to confirm the role of sumoylated C/EBPα in BPD rats, SUMO1 was knocked down by lentiviral transfection of neonatal rat lungs with SUMO1-RNAi-LV. We found that the expression of C/EBPα and surfactant proteins increased following SUMO1 knockdown. Furthermore, the relatively low decrease in the levels of C/EBPα sumoylation was correlated with reduced glycogen consumption. Besides, co-immunoprecipitation assays revealed that sumoylation is involved in the regulation of the interaction between C/EBPα and TGFβ2 in the lung. In conclusion, our findings indicate that sumoylation may act as a negative regulator of the C/EBPα-mediated transactivation in BPD rats.


Unreliable supply of potable water and elevated Aedes aegypti larval indices: a causal relationship?
We investigated the hypothesis that a deficient supply of piped water was causing a high prevalence of water storage containers, which in turn, become important aquatic habitats of Aedes aegypti in a small town in Venezuela. The House (71.2%) and Breteau indices (229) were considerably elevated. Prevalent positive containers were: metal drums, small disposable containers (bottles, tins, etc.), tires, house plants (flowers in vases and plants in pots with earth) and tanks. Most people reported frequent interruptions in the supply of piped water and considered it to be unreliable. The frequency of interruptions in the supply of water was positively correlated with the House and Container indices, and with the number of positive containers, water-storage devices and positive water-storage devices per house. Even people who considered that they had an adequate supply of water kept numerous water storage containers. Most people (60%) said they would not stop storing water even in the event of the establishment of a reliable supply of piped water.


Association of small CAB-like proteins (SCPs) of Synechocystis sp. PCC 6803 with Photosystem II.
The cyanobacterial small CAB-like proteins (SCPs) are one-helix proteins with compelling similarity to the first and third transmembrane helix of proteins belonging to the CAB family of light-harvesting complex proteins in plants. The SCP proteins are transiently expressed at high light intensity and other stress conditions but their exact function remains largely unknown. Recently we showed association of ScpD with light-stressed, monomeric Photosystem II in Synechocystis sp. PCC 6803 (Yao et al. J Biol Chem 282:267-276, 2007). Here we show that ScpB associates with Photosystem II at normal growth conditions. Moreover, upon introduction of a construct into Synechocystis so that ScpB is expressed continuously under normal growth conditions, ScpE was detected under non-stressed conditions as well, and was copurified with tagged ScpB and Photosystem II. We also report on a one-helix protein, Slr1544, that is somewhat similar to the SCPs and whose gene is cotranscribed with that of ScpD; Slr1544 is another member of the extended light-harvesting-like (Lil) protein family, and we propose to name it LilA.


Comparative study of various delivery methods for the supply of alpha-ketoglutarate to the neural cells for tissue engineering.
Delivery of growth factors or bioactive molecules plays an important role in tissue engineering, as the duration to which these are supplied can modulate the cell fate. Thus, the delivery method plays an important role, and the same is presented in this work wherein the exogenous supply of alpha-ketoglutarate ( α -KG) gave better results for fast proliferating cells as compared to delivery by microspheres or microspheres incorporated scaffolds which can be used while culturing slow growing cells. All these studies were performed in two dimensional (2D) and three dimensional (3D) setups in which chitosan-gelatin-polypyrrole has been used as 3-D scaffolds. Chitosan and gelatin microspheres alone as well as incorporated in the cryogels were characterized. MTT assay done using neuro-2a cell line showed approximately 42% and 70% increment in cellular proliferation when gelatin and chitosan microspheres were added in a 3-D setup, respectively, as compared to the control. Biochemical analysis of ammonia showed 6-fold reductions in ammonia level in a 3-D setup compared to the control. We also studied the synthesis of a neurotransmitter-like glutamate and found that its concentration increased up to 0.25 mg/ml when the microspheres were added exogenously in a 3-D system.


Late and chronic Lyme disease.
This article reviews the late and chronic manifestations of Lyme disease. Special attention is given to the chronic manifestations of the disease, detailing its pathogenesis, clinical spectrum, and laboratory criteria for the diagnosis. Based on experimental evidence and experience, approaches to the successful treatment of the late and chronic disease are outlined. Much additional work is needed to improve the understanding of the underlying pathophysiology of the disease, its diagnosis and treatment.


G-protein modulators alter the swimming behavior and calcium influx of Paramecium tetraurelia.
To assess the potential role of G-proteins in chemokinesis, Paramecium tetraurelia was pre-incubated with the G-protein modulator pertussis toxin. Pertussis toxin pretreatment significantly reduced Paramecium chemoattraction to sodium acetate and ammonium chloride in T-maze behavioral assays and depressed the frequency of avoidance reactions, indicating that heterotrimeric G-proteins may be involved with the motility response. To determine whether G-proteins exert their effect via the ciliary voltage-sensitive calcium channel, we examined responses of P. tetraurelia to the potent voltage-sensitive calcium channel agonist, deltamethrin. Pertussis toxin preincubation significantly reduced the toxic effects of deltamethrin exposure as determined by survival under depolarizing conditions and reduced the duration of backward swimming episodes in behavioral bioassays. Furthermore, non-hydrolyzable analogs of guanine nucleotides altered deltamethrin-stimulated calcium influx via calcium channels in isolated ciliary vesicles. Heterotrimeric G-protein subunits were subsequently detected in ciliary vesicles of P. tetraurelia by antibodies produced against Galpha and Gbeta subunits, and by 32P-ADP-ribosylation, indicating that proteins of the appropriate molecular weight are the target of pertussis toxin in these vesicles. These findings provide additional evidence that heterotrimeric G-proteins are associated with ciliary vesicles and that they play a role in the modulation of swimming behavior and the toxic action of deltamethrin in Paramecium.


Cutaneous lupus erythematosus with histopathologic changes restricted to the acrosyringia.
Cutaneous lupus erythematosus may present as an isolated condition or as part of a systemic disease, being acute cutaneous lupus erythematosus, the skin manifestation, more closely related to systemic involvement. The histopathologic findings may show a wide variety of features, which show overlap among different clinical presentations. The exclusive involvement of the eccrine units, including eccrine coils, dermal ducts, and acrosyringia is extremely uncommon. We present the second case of systemic lupus erythematosus (SLE) with histopathologic involvement mostly located in the acrosyringia. The patient was a 37-year-old male with multiorgan failure who, in the context of flare-up of SLE, presented cutaneous lesions consisting of erythematous and edematous macules and plaques on the face, arms, and anterior chest. Histopathologic examination demonstrated necrotic keratinocytes confined to the acrosyringia as the main finding. It was associated with sparse inflammatory infiltrate in the superficial dermis, mostly composed of lymphocytes. The epidermis between the acrosyringia was spared. Our case was clinically almost identical to the one previously described, being a patient with a severe SLE and widespread cutaneous involvement and receiving treatment in the intensive care unit. The main differential diagnosis, both clinically and histopathologically was drug-related erythema multiforme. Clinicopathologic correlation is necessary to establish a correct diagnosis. SLE with histopathologic involvement mostly of the acrosyringia is a rare histopathologic variant of the disorder.


A prospective study of hemodynamic changes associated with distal arterial bypass in the leg.
Twelve limbs with Buerger's disease were examined by measurement of segmental blood pressure, digital arterial oxygen saturation and flow velocity in the foot, before and after distal arterial bypass grafting. Eight out of 12 grafts were patent in a follow-up of 6 months to 2 years and one month. Patients with low distal blood pressure before operation obtained a small increase of the foot and toe pressures postoperatively, whereas patients with relatively good initial distal blood pressure were likely to acquire a remarkable recovery of the foot and toe blood pressures. In all 8 limbs with successful revascularization, blood flow velocity in the foot returned to normal, while the foot or the toe pressures remained pathological in 7 of the 8 limbs and digital arterial oxygen saturation did not revert to normal in 4 limbs, with ulceration after healing of the lesion. Postoperative normalization of the foot flow velocity was predictive of limb salvage. The most characteristic feature of peripheral arterial occlusive disease is a stagnation in the microvascular circulation and improvement of the reduced flow velocity is a goal of surgical or conservative treatment.


Medical treatments of elderly, French patients with type 2 diabetes: results at inclusion in the GERODIAB Cohort.
Prevalence of diabetes in the elderly increases, and half of the French diabetics are over the age of 75 years. The GERODIAB study is the first French multicentre, prospective, observational study designed to analyse over 5 years the influence of glycaemic control on morbidity-mortality in type 2 diabetics patients 70 years old and over. This study analysed the diabetic and geriatric factors associated with the treatment modalities, particularly insulin, at inclusion in the cohort. The cohort of 987 type 2 diabetics was divided into three groups according to the method of treatment. Slightly fewer than one-third of these patients (26.4%) were treated with insulin alone, 31% received insulin and oral antidiabetic drugs, and 42.7% oral antidiabetic drugs alone. The patients that received insulin alone were significantly older, had poorer glycaemic control (HbA1c = 7.9 ± 1.4, 7.8 ± 1.0 and 7.1 ± 1.2%, respectively; P < 0.001) and had greater alterations of glomerular filtration rate (GFR). HbA1c was below 6.5% in 15% of patients and 37.3% of patients had a GFR below 60 mL/min. The patients treated with insulin alone had significantly more hypoglycaemic episodes (respectively 53.3, 36.3 and 19.5%, P < 0.001), retinopathy, cardiovascular involvement and more specific geriatric complications, such as cognitive disorders (respectively 34.1, 31.4 and 23.6%, P = 0.006). In this specific population of elderly type 2 diabetic patients, diabetic and geriatric conditions significantly differed between the types of drug treatments. Considering low values of HbA1c and GFR, some patients seemed overtreated and other patients received inappropriate drugs.


Factors associated with length of stay in hospital for suspected community-acquired pneumonia.
To determine factors associated with the length of stay (LOS) for patients with suspected community-acquired pneumonia (CAP) who required hospitalization for treatment. The authors studied a population-based prospective cohort of 2,757 adults with suspected CAP who were admitted over a two-year period. Logistic regression, multiple linear regression, and classification and regression trees were used to determine the factors associated with LOS. The study was conducted in two community and tertiary care hospitals, two community and secondary care hospitals, and two community hospitals in the Capital Health Region of Edmonton, Alberta. Symptoms such as sweats, shaking chills and wheezing were associated with an LOS of seven days or shorter, whereas weight loss, functional impairment, heart, renal or neoplastic diseases and time to first dose of antibiotic were predictive of an LOS greater than seven days. Regression tree analysis indicated that rapid achievement of physiological stability was associated with a shorter LOS. The use of an indwelling urinary catheter was found to be an important determinant of LOS. The present study found several new associations with increased LOS in patients with CAP, including functional status, time to receipt of first dose of antibiotic therapy, use of certain antibiotics, presence of a urinary catheter and the importance of time to physiological stability. An intervention targeting avoidance of urinary catheters may be associated with a shorter LOS.


The complications of male hypogonadism: is it just a matter of low testosterone?
The history of diagnosing hypogonadism and hypotestosteronemia shows us the many steps that were necessary to achieve our current knowledge and the ability to improve these patients' well-being. Moreover, so far, criteria for diagnosing hypotestosteronemia varies according to the underlying condition, and according to the consensus or guideline adopted. Furthermore, besides the many signs and symptoms, there are several complications associated with low testosterone levels such as osteoporosis, metabolic alterations, as well as cardiovascular disorders. However, data are often conflicting regarding the severity, timing or even the real clinical relevance of these complications, although these studies often lack essential information such as gonadotropin levels or the underlying cause of hypogonadism. The present review focus on the complications of male hypogonadism according to the cause of testosterone deficiency, highlighting the lack of information found in many studies investigating its effects. We thereby stress the necessity to always perform a complete evaluation of the type of hypogonadism (including at least gonadotropins and secondary causes) when investigating the effects of low testosterone levels.


[Diagnosis and treatment of primary germ cell tumors of the mediastinum. Report of six cases].
Primary germ cell tumours of the mediastinum are rare. We report a retrospective study of six cases. Sex ratio was 2/1. The tumor site was the posterior mediastinum in two patients and anterior in the remaining cases. High level serum markers was noted in two patients. At histologic exam we found two cases of seminoma, one embryonal carcinoma, one case of yolk sac tumor and two cases of composite tumor. All patients had non metastatic but locally advanced disease at diagnosis. Three patients were treated with cisplatin based chemotherapy followed by radiotherapy or surgical resection of residual masses. Only one patient is still alive. As it is often reported in the literature, the prognosis of this disease is poor especially for non seminomatous tumours.


Early and delayed evaluation of solid tumours with 64Cu-ATSM PET/CT: a pilot study on semiquantitative and computer-aided fractal geometry analysis.
The aim of this study was to analyse early and delayed acquisition on copper-64 diacetyl-bisN4-methylthiosemicarbazone (Cu-ATSM) PET/CT in a small cohort of patients by comparing semiquantitative and computer-aided fractal geometry analyses. Five cancer patients, including non-small-cell lung cancer and head and neck cancer, were investigated with Cu-ATSM PET/CT. Participants received an intravenous injection of Cu-ATSM according to body size and were imaged 60 min (early) and 16 h (delayed) later on hybrid PET/CT. Reconstructed images were visualized on advanced workstations for the definition of semiquantitative parameters: standardized uptake value (SUV)max, SUVratio-to-muscle, SUVmean, hypoxic volume (HV) and hypoxic burden (HB=HV×SUVmean). DICOM data retrieved from both scans were analysed using an ad-hoc computer program to determine the mean intensity value, SD, relative dispersion, three-dimensional histogram fractal dimension and three-dimensional fractal dimension. All tumour lesions showed increased uptake of Cu-ATSM at early evaluation, with a median SUVratio-to-muscle of 4.42 (range: 1.58-5.62), a median SUVmax of 5.3 (range: 1.9-7.3), a median SUVmean of 2.8 (range: 1.5-3.9), a median HV of 41.6 cm (range: 2.8-453.7) and a median HB of 161.5 cm (range: 4.4-1112.5). All semiquantitative data obtained at 1 h were consistent with the parameters obtained on delayed imaging (P>0.05). A borderline statistically significant difference was found only for SUVmax of the muscle (P=0.045). Fractal geometry analysis on DICOM images showed that all parameters at early imaging showed no statistically significant difference with late acquisition (P>0.05). Our findings support the consistency of Cu-ATSM PET/CT images obtained at early and delayed acquisition for the assessment of tumour lesions.


Sperm survival and transport in the female reproductive tract.
Fertilization failure, mostly due to absence of sperm in the oviducts, is a major cause of reproductive inefficiency of farm animals. Sperm may be transported to the oviducts of cattle and sheep within a few minutes after mating or insemination, but these sperm probably fertilize few ova. Slower transport, with establishment of sperm populations in each segment of the reproductive tract, requires a few to several hours. In swine, sperm capable of fertilizing ova reach the oviducts in less than 1 h. Smooth muscle contractions of the reproductive tract, ciliary beats, fluid currents, and flagellar activity of sperm are primary mechanisms of sperm transport. Sperm become hyperactive in the oviducts in association with capacitation. Most sperm in an inseminate drain from the female reproductive tract within a few minutes or hours after insemination; remaining sperm are removed from the tract by slower drainage or phagocytosis. Sperm survival and transport in estrous ewes is reduced drastically by pastures with high estrogen content and by regulating estrus with progestogen or prostaglandin F2 alpha. The cervix is the initial site of inhibition of sperm transport in ewes, and endocrine imbalances probably are the basis of inhibition. Sperm transport problems generally are associated with immobilization and death of sperm in the uterus and anterior segments of the cervix within 2 h after mating. After gilts are inseminated with frozen-thawed semen, relatively few sperm are retained in the reproductive tract, apparently accounting for lowered fertilization rates. Sperm transport has been improved by adding to semen or administering to females such compounds as prostaglandin F2 alpha, oxytocin, estradiol, phenylephrine, or ergonovine. Estradiol, prostaglandin F2 alpha, phenylephrine, and ergonovine administered to rabbits at insemination each increased fertilization rates.


Developmental competence of bovine oocytes frozen at different cooling rates.
Experiments were conducted to determine the optimal cooling conditions for improving the developmental competence of in vitro-matured bovine oocytes when frozen in 1.6 M 1,2-propanediol. Bovine oocytes were cooled from 0 degree to -5.5 degrees C at 1 degree C/min, seeded, and then cooled to -30 degrees C at different cooling rates (0.3 degree, 0.6 degree or 0.9 degree C/min) and then plunged into LN2. When frozen-thawed oocytes were fertilized in vitro, the proportions of fertilization and developmental competence did not differ among the three groups frozen at different cooling rates. The findings indicated that a cooling rate of less than 1.0 degree C/min in the freezing procedure did not affect the developmental competence of postthaw in vitro-matured bovine oocytes.


Oligomeric structure of the repressor of the bacteriophage Mu early operon.
The regulation of the lytic and lysogenic development in the life cycle of bacteriophage Mu is regulated in part by its repressor, c, which binds to three operator sites, O1, O2 and O3, overlapping two divergent promoters. The oligomeric structure of this repressor protein was investigated by hydrodynamic and biochemical methods. Size-exclusion chromatography, analytical ultracentrifugation, dynamic light scattering, crosslinking and direct electron microscopy observations suggest that c exists primarily as a hexamer with a molecular mass of 120-140 kDa at low concentrations, i.e. in the 10-microM range. This molecule undergoes a self-assembly process leading to dodecamers and higher order species as the concentration is further increased in a manner depending on the nature of the solvent. Our results also suggest that these species have an elongated structure, and a possible arrangement of the subunits within the hexamer is proposed. The implication of this unusual quaternary structure for a repressor in its interaction with the operator sites O1 and O2 remains to be elucidated.


[Operative theatment of male pseudohermaphroditism (author's transl)].
The operative treatment of two patients with male pseudohermaphroditism is reported. The patients reported were girls whose psychosexual attitude indicated a male sexual change. During several procedures the vagina was removed, the urethra was extended according to the method of Denis-Browne and a functioning penis was formed using a skin flap plasty supported by rib cartilage or an artificial prosthesis.