Cytotoxic activity in the coelomic fluid of the annelid Eisenia foetida Sav.
The annelid Eisenia foetida not only causes hemolysis of red blood cells of several vertebrate species, but also has a toxic effect on a variety of cell types, such as chicken fibroblasts, guinea-pig polymorphonuclear leukocytes and insect hemocytes. However, it has no influence on the vitality of the coelomocytes of Lumbricus terrestris and other lumbricides, nor on the hemocytes of the snail Helix pomatia, the mussels Anodonta cygnea and Unio tumidus, free cells of the turbellarian Euplanaria sp. or whole Rhabditis oxycerca (nematode) and the protozoons Paramaecium caudatum and an amoeba of the Proteus-type. By electrofocussing the hemolytic activity of pooled coelomic fluid was separated into 7 hemolytic bands. Three of them are cytotoxic. The cytotoxic effect is a result of the destruction of the cell membrane, as shown by measuring the release of lactate dehydrogenase (LDH). The bacteriostatic and bacteriocidal action of the coelomic fluid of E. foetida against a broad spectrum of gram positive and gram negative bacteria was tested. An antibacterial activity could be observed only against Proteus vulgaris and Bacillus megaterium. It was noted that the so-called Eisenia foetida-factor acts on an antigenic structure at the cell surface when anti-sheep-E-antibody was used under competitive conditions. The binding between the Eisenia foetida-factor and this membrane structure is relatively strong as it cannot be removed by subsequent treatment with anti-sheep-E-antibody or 2 M KCl.


The 5XFAD mouse model of Alzheimer's disease displays age-dependent deficits in habituation to a novel environment.
Habituation is a form of learning characterized by a decrement in responsiveness to a stimulus that is repeated or prolonged. In rodents, habituation to a novel environment is characterized by a decrease in locomotion over time spent in a novel environment. Habituation to a novel environment is dependent on hippocampal function, suggesting that habituation behavior may be a relevant readout for hippocampal-dependent memory deficits that are characteristic of Alzheimer's disease (AD). Current assays that measure hippocampal-dependent memory in preclinical animal models of AD have not accurately predicted the cognitive protection of novel interventions in human trials. Here, we tested whether a behavioral habituation paradigm could detect age-associated changes in a common preclinical mouse model of AD-like amyloid pathology, the 5XFAD mouse. We exposed 5XFAD mice and age-matched wild-type (WT) littermates at 3, 6, and 9 months of age to a novel environment over two sessions separated by 24 h and measured their locomotion. WT mice habituated to the novel environment over time, while 5XFAD mice displayed age-dependent deficits in behavioral habituation. We replicated our results using publicly available open field data from 5XFAD and late-onset AD mouse models with TREM2*R47H and APOE4 mutations. Overall, we present behavioral habituation as a potentially sensitive task to assess age-associated behavioral deficits in 5XFAD mice and other mouse models of AD that could be used to test the preclinical efficacy of novel AD therapeutics.


Post Pelvic Radiotherapy Affectation of the Lower Urinary Tract Peripheral Innervation in Men.
The periurethral electromyography (EMGs) alterations in men who underwent pelvic radiotherapy (RT), either isolated or combined with surgery, have not been frequently described in the literature. The study aimed to compare the EMG's data in men undergoing RT versus the non-irradiated control group. The study included 61 consecutive males, who had undergone RT (27 of them had been operated) and 99 control consecutive patients who underwent a retrospective assessment. The EMGs were performed using a concentric electrode needle perineally, localizing the sphincter by visual and auditory signal (electromyograph MMS Solar Active). 14.8% denervation, 62.9% reinnervation, 14.9% denervation + reinnervation and 7.4% EMG normal. The age (p < 0.001) and neurogenic bladder data (p < 0.001) are risk factors. The smaller the prostate size (obtained by rectal examination) post-RT, the more the chance for an abnormal EMG (p < 0.001). The fact of having had received RT (p < 0.001) is the only risk factor. RT produces lesions over the pudendal nerve, showing denervation even in late periods. The surgery did not behave as a risk factor.


Aziridine-2,3-dicarboxylate-based cysteine cathepsin inhibitors induce cell death in Leishmania major associated with accumulation of debris in autophagy-related lysosome-like vacuoles.
The papain-like cysteine cathepsins expressed by Leishmania play a key role in the life cycle of these parasites, turning them into attractive targets for the development of new drugs. We previously demonstrated that two compounds of a series of peptidomimetic aziridine-2,3-dicarboxylate [Azi(OBn)(2)]-based inhibitors, Boc-(S)-Leu-(R)-Pro-(S,S)-Azi(OBn)(2) (compound 13b) and Boc-(R)-Leu-(S)-Pro-(S,S)-Azi(OBn)(2) (compound 13e), reduced the growth and viability of Leishmania major and the infection rate of macrophages while not showing cytotoxicity against host cells. In the present study, we characterized the mode of action of inhibitors 13b and 13e in L. major. Both compounds targeted leishmanial cathepsin B-like cysteine cathepsin cysteine proteinase C, as shown by fluorescence proteinase activity assays and active-site labeling with biotin-tagged inhibitors. Furthermore, compounds 13b and 13e were potent inducers of cell death in promastigotes, characterized by cell shrinkage, reduction of mitochondrial transmembrane potential, and increased DNA fragmentation. Transmission electron microscopic studies revealed the enrichment of undigested debris in lysosome-like organelles participating in micro- and macroautophagy-like processes. The release of digestive enzymes into the cytoplasm after rupture of membranes of lysosome-like vacuoles resulted in the significant digestion of intracellular compartments. However, the plasma membrane integrity of compound-treated promastigotes was maintained for several hours. Taken together, our results suggest that the induction of cell death in Leishmania by cysteine cathepsin inhibitors 13b and 13e is different from mammalian apoptosis and is caused by incomplete digestion in autophagy-related lysosome-like vacuoles.


Placement of cast restorations over direct pulp capping procedures: a decision analytic approach.
A review of the literature shows a significant amount of controversy regarding the success of pulp capping procedures, with the average clinically evaluated pulp capping success being 81%, and 75% when evaluated histologically. This study evaluated the costs and benefits of a pulp cap versus endodontic therapy for a tooth that is to receive a cast restoration, and determined what level of success is needed for pulp capping to be the preferred treatment.


Circular dichroism of the non-enzymatic browning products of poly-L-lysine and albumin.
Poly-L-lysine (PLL) and bovine serum albumin were used as models in the investigation of non-enzymatic glycation and browning reaction by circular dichroism measurements. Different sugars (glucose, glucose-6-P and ribose) induced different extents of reaction and produced different chromophores that absorbed light in the near u.v. region. All glycated samples gave a common spectral feature in absorption and blue fluorescence, but they gave distinctly different near u.v. c.d. features, indicating that the browning products containing yellow chromophores are different for glycated samples and may have rigid moieties. The ribocated PLL (at pH 11.0, alpha-helix) and albumin were unable to convert completely to beta-conformation upon heating, indicating that browning reaction may have changed the tertiary structure.


Large-scale isolation and purification of geniposide from the fruit of Gardenia jasminoides Ellis by high-speed counter-current chromatography.
High-speed counter-current chromatography (HSCCC) was applied to the isolation and purification of geniposide from Gardenia jasminoides Ellis. Analytical HSCCC was used for the preliminary selection of a suitable solvent system composed of ethyl acetate-n-butanol-water (2:1:3, v/v/v). According to the above solvent system, preparative HSCCC was successfully performed with the optimal solvent system composed of ethyl acetate-n-butanol-water (2:1.5:3, v/v/v) yielding 389 mg of geniposide at over 98% purity from 1g of the partially purified extract with 38.9% recovery in a one-step separation.


Mortality on the waiting list for coronary artery bypass grafting: incidence and risk factors.
Insufficient capacity for coronary artery bypass grafting results in waiting times before operation, prioritization of patients and, ultimately, death on the waiting list. We aimed to calculate waiting list mortality and to identify risk factors for death on the waiting list. The study included 5,864 consecutive patients accepted for elective coronary artery bypass grafting (78% male; mean age, 66 +/- 9 years). The patients were categorized at acceptance into three priority groups: imperative (39%), urgent (36%), or routine (25%). Waiting list mortality was calculated and compared between groups, and risk factors were identified by Poisson regression. Median waiting time for the whole population was 55 days. Seventy-seven patients (1.3%) died, corresponding to a mortality rate of 5.8 deaths per 100 patient-years. The mortality rate per 100 patient-years was highest for those in the imperative group, 15.1 deaths, compared with 5.3 deaths in the urgent group and 3.2 in the routine group (p < 0.001). Independent risk factors were male sex (p = 0.032), Cleveland Clinic risk score (p = 0.005), impaired left ventricular ejection fraction (p = 0.007), unstable angina pectoris (p = 0.001), concomitant aortic valve disease (p = 0.002), priority group (p < 0.001), and time after acceptance (p = 0.019). The mortality risk increased with time after acceptance by 11% a month. Long waiting lists for coronary artery bypass grafting are associated with considerable mortality. The risk of death increases significantly with waiting time. Sex, unstable angina, perioperative risk, impaired left ventricular function, and concomitant aortic valve disease are independent risk factors and should be considered at triage.


A newly identified photolyase from Arthrospira platensis possesses a unique methenyltetrahydrofolate chromophore-binding pattern.
Cyclobutane pyrimidine dimers (CPD), as a common DNA damage caused by UV radiation, often lead to skin cancer. Here, we identified a photolyase from the alga Arthrospira platensis (designated as Ap-phr), which has been regarded as a safe organism for humans for centuries, that can efficiently repair CPD lesions in ssDNA and dsDNA in vitro. The 1.6 Å resolution crystal structure of Ap-phr revealed that it possesses a unique methenyltetrahydrofolate chromophore-binding pattern with high energy transfer efficiency. Our study of Ap-phr highlights its potential use in cosmetic, industrial and aesthetic medicine applications.


Comprehensive metabolomic analysis of Mangifera indica leaves using UPLC-ESI-Q-TOF-MSE for cell differentiation: An in vitro and in vivo study.
The comprehensive metabolic profiling was performed in the leaf extracts of Mangifera indica and assessed for their significant therapeutic application in tissue engineering and regenerative medicine in both in vitro and in vivo studies. About 147 compounds were identified in the ethyl acetate and methanol extracts of M. indica using MS/MS fragmentation analysis and the selected compounds were quantified using LC-QqQ-MS analysis. The in vitro cytotoxic activity showed that the M. indica extracts enhance the proliferation of mouse myoblast cells in concentration-dependent manner. As well, the extracts of M. indica induce the myotube formation by generating oxidative stress in the C2C12 cells was confirmed. The western blot analysis clearly showed that the M. indica induce myogenic differentiation by upregulating the myogenic marker proteins such as PI3K, Akt, mTOR, MyoG, and MyoD. The in vivo studies showed that the extracts expedites the acute wound repair by formation of crust, wound closure and improves the blood perfusion towards the wound area. Together, the leaves of M. indica can be used as excellent therapeutic agent for tissue repair and wound healing applications.


East Asian summer monsoon enhanced by COVID-19.
Anthropogenic emissions decreased dramatically during the COVID-19 pandemic, but its possible effect on monsoon is unclear. Based on coupled models participating in the COVID Model Intercomparison Project (COVID-MIP), we show modeling evidence that the East Asian summer monsoon (EASM) is enhanced by 2.2% in terms of precipitation and by 5.4% in terms of the southerly wind at lower troposphere, and the amplitude of the forced response reaches about 1/3 of the standard deviation for interannual variability. The enhanced EASM during COVID-19 pandemic is a fast response to reduced aerosols, which is confirmed by the simulated response to the removal of all anthropogenic aerosols. The observational evidence, i.e., the anomalously strong EASM observed in 2020 and 2021, also supports the simulated enhancement of EASM. The essential mechanism for the enhanced EASM in response to COVID-19 is the enhanced zonal thermal contrast between Asian continent and the western North Pacific in the troposphere, due to the reduced aerosol concentration over Asian continent and the associated latent heating feedback. As the enhancement of EASM is a fast response to the reduction in aerosols, the effect of COVID-19 on EASM dampens soon after the rebound of emissions based on the models participating in COVID-MIP. The online version contains supplementary material available at 10.1007/s00382-022-06247-8.


How much the leg length has changed after the MOUKA through measurement of the full length radiographs? Beware of splicing error.
Leg length change after knee arthroplasty is one of the most concerned problems for patients and doctors. However, as there was only one literture focused on the leg length change after unicompartmental knee arthroplasty, we aimed to clarify the leg length change after medial mobile-bearing unicompartmental knee arthroplasty (MOUKA) using a novel double calibration method. We enrolled patients who underwent MOUKA and had taken full-length radiographs in a standing position prior to and at 3 months after the operation. We eliminated the magnification by a calibrator and corrected the longitudinal splicing error by measuring the femur and tibia lengths before and after operation. Perceived leg length change was collected 3 months after operation. Bearing thickness, preoperative joint line convergence angle, preoperative and postoperative varus angles, flexion contracture and Oxford knee score (OKS) were also collected. From June 2021 to February 2022, 87 patients were enrolled.76 (87.4%) of them showed an increase with an average of 0.32 cm (range from -0.30 cm to 1.05 cm) in leg length change. The lengthening was strongly correlated with the degree of varus deformity and its correction value (r = 0.81&0.92, P < 0.01). Only 4 (4.6%) patients perceived leg length lengthening after operation. There was no difference in OKS between the patients who had an increase in leg length and those who had a decrease (P = 0.99). Majority of patients only experienced a slight increase in leg length after MOUKA, and such an increase did not affect patients' perception and short-term function.


Interferon induction in turkeys by oral administration of the imidazoquinolinamine S-28828 and modulation of the pathogenesis of Escherichia coli.
A synthetic imidazoquinolinamine, S-28828, has been shown to be an effective antiviral and antitumor agent in mammals. This immune modifier induces a number of cytokines such as interferons, tumor necrosis factor-alpha, interleukins and granulocyte-macrophage colony-stimulating factors in mammals. We showed that when turkeys were given S-28828 orally, high serum titers of IFN were induced in a dose-dependent manner. Turkeys, once stimulated by S-28828, became refractory to IFN production by repeated stimulation. S-28828 induced spleen, bone marrow and peripheral leukocytes to produce IFN in vitro. Splenic adherent cells were the main producers of IFN after in vitro stimulation. S-28828-induced IFN was identified as type I IFN that was pH-resistant but heat-labile. We examined the effect of a high dose (100 mg kg(-1) body weight) of S-28828 on the pathogenesis of E. coli in turkeys. Treatment with S-28828 increased mortality in infected birds and impaired E. coli clearance from the liver. The enhancement of the pathogenicity of E. coli by S-28828 may have been due to the massive release of cytokines inducing a shock-like syndrome in infected turkeys.


Cloning and expression of the carbaryl hydrolase gene mcbA and the identification of a key amino acid necessary for carbaryl hydrolysis.
Carbamate hydrolase is the initial and key enzyme for degradation of carbamate pesticides. In the present study, we report the isolation of a carbaryl-degrading strain Pseudomonas sp. XWY-1, the cloning of its carbaryl hydrolase gene (mcbA) and the characterization of McbA. Strain XWY-1 was able to utilize carbaryl as a sole carbon source and degrade it using 1-naphthol as an intermediate. Transposon mutagenesis identified a mutant of XWY-1M that was unable to hydrolyze carbaryl. The transposon-disrupted gene mcbA was cloned by self-formed adaptor PCR, then expressed in Escherichia coli BL21(DE3) and purified. McbA was able to hydrolyze carbamate pesticides including carbaryl, isoprocarb, fenobucarb, carbofuran efficiently, while it hydrolyzed aldicarb, and propoxur poorly. The optimal pH of McbA was 7.0 and the optimal temperature was 40°C. The apparent Km and kcat values of McbA for carbaryl were 77.67±12.31μM and 2.12±0.10s-1, respectively. Three amino acid residues (His467, His477 and His504) in the predicted polymerase/histidinol phosphatase-like domain were shown to be closely related to the activity of McbA, with His504 being the most important, as a replacement of His504 led to the complete loss of activity. This is the first study to identify key amino acids in McbA.


An autopsy case of massive pulmonary tumor embolism due to undiagnosed prostatic adenocarcinoma.
Adenocarcinoma of the prostate is occasionally associated with pulmonary embolism, occurring as a result of secondary hypercoagulable states or cancer-associated emboli. The objective of this study was to provide a review of clinical, histopathological and immunohistochemical features of poorly differentiated prostatic adenocarcinoma, emphasizing the relevance of undiagnosed malignancy as a cause of pulmonary embolism. The current study describes the case of a 78-year-old male who experienced remarkable clinical symptoms suggestive of pulmonary embolism. Following several diagnostic examinations, the patient was diagnosed with pulmonary embolism, which led to the detection of prostatic adenocarcinoma. Poorly differentiated adenocarcinoma with a Gleason's score of nine was set as a definite diagnosis. Multiple tumor emboli within small and medium-sized pulmonary blood vessels were found in all specimens taken from lung tissue. Immunohistochemical analysis showed diffuse and strong positivity of tumor cells within pulmonary arteries. Hidden malignancy is a diagnostic challenge that should be considered in the differential diagnosis of pulmonary embolism. Laboratory and radiological findings with additional histopathological evaluation are needed for the definite diagnosis.


Effects of plastic film residues on occurrence of phthalates and microbial activity in soils.
Plastic film mulching has played an important role in Chinese agriculture, especially in vegetable production, but large amounts of film residues can accumulate in the soil. The present study investigated the effects of plastic film residues on the occurrence of soil PAEs and microbial activities using a batch pot experiment. PAE concentrations increased with increasing plastic film residues but the soil microbial carbon and nitrogen, enzyme activities and microbial diversity decreased significantly. At the end of the experiment the PAE concentrations were 0-2.02 mg kg(-1) in the different treatments. Soil microbial C and N, enzyme activities, AWCD value, and Shannon-Weaver and Simpson indices declined by about 28.9-76.2%, 14.9-59.0%, 4.9-22.7%, 23.0-42.0% and 1.8-18.7%, respectively. Soil microbial activity was positively correlated with soil PAE concentration, and soil PAE concentrations were impacted by plastic color and residue volume. Correlations among, and molecular mechanisms of, plastic film residues, PAE occurrence and microbial activity require further study.


Determination of piroxicam by solid-phase spectrophotometry in a continuous flow system.
A simple flow injection UV spectrophotometric method was developed for the determination of piroxicam. The method is based on its transient retention and concentration on Sephadex DEAE-A-25 anion-exchange gel beads packed in the flow cell and the continuous monitoring of its native absorbance on the solid phase at 354 nm. The sample was injected into a 0.1 M NaCl carrier stream at pH 9.5 by using a simple monochannel FIA manifold. When the analytical signal reached a maximum value, piroxicam was eluted from the solid support by means of a desorbing solution (0.2 M, pH 4.5). The response of the sensor was linear in the concentration range 0.5-10 microg ml(-1) with a R.S.D. (%) of 1.8, a detection limit (3 sigma criterion) of 0.1 microg ml(-1) and a sampling rate of 13 h(-1). Application to the analysis of pharmaceutical samples testifies to the utility of this sensor. The accuracy of the proposed method was better than 5%.


[Magnetic resonance spectroscopy. Part 2: Application in diagnosis and clinical research].
MR spectroscopy creates a noninvasive window into the metabolism of normal and diseased tissue in vivo. The physics and the measurement techniques being described in part I, this contribution presents the potential use of MRS in patient healthcare and clinical research. We discuss applications of MRS to neurooncology, to oncology outside the central nervous system and to nononcological diseases.


YouTube as a Potential Training Resource for Laparoscopic Fundoplication.
To analyze the surgical proficiency and educational quality of YouTube videos demonstrating laparoscopic fundoplication (LF). In this cross-sectional study, a search was performed on YouTube for videos demonstrating the LF procedure. The surgical and educational proficiency was evaluated using the objective component rating scale, the educational quality rating score, and total video quality score. Statistical significance was determined by analysis of variance, receiver operating characteristic curve, and odds ratio analysis. A total of 71 videos were included in the study; 28 (39.4%) videos were evaluated as good, 23 (32.4%) were moderate, and 20 (28.2%) were poor. Good-rated videos were significantly longer (good, 22.0 ± 5.2min; moderate, 7.8 ± 0.9min; poor, 8.5 ± 1.0min; p = 0.007) and video duration was predictive of good quality (AUC, 0.672 ± 0.067; 95% CI: 0.541-0.802; p = 0.015). For good quality, the cut-off video duration was 7:42 minute. This cut-off value had a sensitivity of 67.9%, a specificity of 60.5%, and an odds ratio of 3.23 (95% CI: 1.19-8.79; p = 0.022) in predicting good quality. Videos uploaded from industrial sources and with a higher views/days online ratio had a higher objective component rating scale and total video quality score. In contrast, the likes/dislikes ratio was not predictive of video quality. Many videos showing the LF procedure have been uploaded to YouTube with varying degrees of quality. A process for filtering LF videos with high surgical and educational quality is feasible by evaluating the video duration, uploading source, and the views/days online ratio. However, alternative videos platforms aimed at professionals should also be considered for educational purposes.


Three-dimensional printing in spine surgery: a review of current applications.
In recent years, the use of three-dimensional printing (3DP) technology has gained traction in orthopedic spine surgery. Although research on this topic is still primarily limited to case reports and small cohort studies, it is evident that there are many avenues for 3DP innovation in the field. This review article aims to discuss the current and emerging 3DP applications in spine surgery, as well as the challenges of 3DP production and limitations in its use. 3DP models have been presented as helpful tools for patient education, medical training, and presurgical planning. Intraoperatively, 3DP devices may serve as patient-specific surgical guides and implants that improve surgical outcomes. However, the time, cost, and learning curve associated with constructing a 3DP model are major barriers to widespread use in spine surgery. Considering the costs and benefits of 3DP along with the varying risks associated with different spine procedures, 3DP technology is likely most valuable for complex or atypical spine disorder cases. Further research is warranted to gain a better understanding of how 3DP can and will impact spine surgery.


Effect of Coronary Slow Flow on the Longitudinal Left Ventricular Function Assessed by 2-Dimensional Speckle-Tracking Echocardiography.
The coronary slow flow phenomenon is defined as the slow progression of an angiographic contrast agent to the distal part of the coronary arteries on selective coronary angiography in the absence of stenosis. There are some studies with different results about the effect of this phenomenon on left ventricular (LV) function. The aim of our study was to evaluate the longitudinal LV function in the coronary slow flow phenomenon using 2-dimensional (2D) speckle-tracking echocardiography. In a study with a patient-to-patient matched design, 36 patients with the coronary slow flow phenomenon and 36 individuals with normal coronary flow matched for age (±5 years), sex, hypertension, and diabetes mellitus were compared in terms of the longitudinal LV systolic and diastolic functions by pulsed wave tissue Doppler echocardiography and 2D speckle-tracking echocardiography-derived indices. Lateral s' and e' waves were lower in the patients with the coronary slow flow phenomenon, but there were no statistically significant differences between the groups regarding the other tissue Doppler echocardiographic indices and longitudinal systolic strain and systolic and diastolic strain rates derived by 2D speckle-tracking echocardiography. Our results showed that the coronary slow flow phenomenon could not impair the longitudinal LV systolic and diastolic functions.


Circadian optimisation of irinotecan and oxaliplatin efficacy in mice with Glasgow osteosarcoma.
The relevance of circadian rhythms in irinotecan and oxaliplatin tolerability was investigated with regard to antitumour activity. Mice bearing Glasgow osteosarcoma (GOS) received single agent irinotecan (50 or 60 mg kg(-1) per day) or oxaliplatin (4 or 5.25 mg kg(-1) per day) at one of six dosing times expressed in hours after light onset (3, 7, 11, 15, 19 or 23 hours after light onset). Irinotecan (50 mg kg(-1) per day) and oxaliplatin (4 or 5.25 mg kg(-1) per day) were given 1 min apart at 7 or 15 hours after light onset, or at their respective times of best tolerability (7 hours after light onset for irinotecan and 15 hours after light onset for oxaliplatin) or worst tolerability (15 hours after light onset for irinotecan and 7 hours after light onset for oxaliplatin). Tumour growth rate was nearly halved and per cent increase in estimated life span (% ILS) was - doubled in the mice receiving irinotecan at 7 hours after light onset as compared to 15 hours after light onset (P<0.05). Results of similar magnitude were obtained with oxaliplatin for both endpoints, yet with 7 hours after light onset corresponding to least efficacy and 15 hours after light onset to best efficacy (P<0.05). Irinotecan addition to oxaliplatin proved therapeutic benefit only if the schedule consisted of irinotecan administration at 7 hours after light onset and oxaliplatin delivery at 15 hours after light onset, i.e. when both drugs were given near their respective "best" circadian times. These would correspond to the middle of the night for irinotecan and the middle of the day for oxaliplatin in humans.


Ruptured Spinal Aneurysms: Diagnosis and Management Paradigms.
Spinal aneurysms (SA) are rare neurovascular pathologies with an unclear natural history and management strategy. We review the clinical and radiologic manifestations, management, and outcome of patients who presented with spinal subarachnoid hemorrhage (SAH) secondary to ruptured spinal aneurysms over a 10-year period. We provide a literature review about this condition and its management. All patients diagnosed with nontraumatic spinal SAH were collected from a single-center prospectively maintained database of patients with SAH between January 2010 and January 2020. Patients diagnosed with spinal aneurysms were reviewed. For each patient, demographic data, clinical presentation, imaging findings, management strategies, and outcomes are reviewed and discussed. Between January 2010 and January 2020, ten patients were diagnosed with nontraumatic spinal SAH (3 patients presented with isolated spinal SAH and 7 patients with concomitant spinal and posterior fossa SAH). Among those, 4 patients were found to have a spinal aneurysm as the cause of SAH. The aneurysms were located in the cervical regions in 3 patients (75%) and at the thoracic level in 1 patient. Two aneurysms (50%) involved the anterior spinal artery, and 2 aneurysms (50%) involved a radiculomedullary artery. One aneurysm was a flow-related aneurysm of the anterior spinal artery in the setting of bilateral vertebral artery occlusion and was treated by surgical clipping with good outcome. Three aneurysms were idiopathic pseudoaneurysms with a negative diagnostic evaluation for secondary causes. These pseudoaneurysms were treated conservatively; 2 patients did well and 1 patient passed away from severe intracranial vasospasm. Two aneurysms resolved on diagnostic angiogram, and 1 aneurysm was absent on initial angiogram and appeared on follow-up diagnostic imaging 3 months later. Spinal aneurysms are rare neurovascular pathologies that should be considered in the setting of spinal and/or posterior fossa subarachnoid hemorrhage. Conservative treatment may be a potential safe alternative to interventional treatment. Before the initiation of surgical or endovascular treatment, spinal angiography should be repeated because of the potential for spontaneous resolution.


Reduced hepatic ischemia/reperfusion injury by IL-4: potential anti-inflammatory role of STAT6.
The ability of interleukin-4 (IL-4) to modulate activation of the transcription factors, NF-kappaB and STAT6, reduce proinflammatory cytokine expression and protect against liver injury induced by ischemia/reperfusion was assessed. C57BL/6 mice underwent 90 minutes of partial hepatic ischemia followed by 1 or 8 h of reperfusion with or without intravenous administration of 1 microg (0.5 microg just prior to ischemia, 0.5 microg at reperfusion) recombinant murine IL-4. Liver expression of TNFalpha mRNA was determined by RT-PCR. Activation of NF-kappaB and STAT6 in liver nuclear extracts was assessed by mobility shift assay. Hepatic ischemia/reperfusion increased hepatic expression of tumor necrosis factor-alpha (TNFalpha), induced significant neutrophil accumulation and liver injury. Treatment with IL-4 greatly suppressed liver TNFalpha mRNA expression, neutrophil accumulation and liver injury. IL-4 had no effect on liver NF-kappaB activation, but greatly increased the activation of STAT6. The data suggest that STAT6 activation by IL-4 may be responsible for the protective effects of this cytokine.


An integrated qualitative and quantitative study on sexual and reproductive health problems faced by women with disabilities in Chandigarh, India.
To estimate the prevalence of sexual and reproductive health (SRH) problems among women with disabilities (WWD) in Chandigarh, India, and to ascertain the difficulties experienced by WWD in accessing hospital services. This cross-sectional study was conducted during 2014 to 2017 in Chandigarh, India. The study participants were women 15 years and older with at least 40% disability. A pretested questionnaire and in-depth interview were used to determine sociodemographic profile, medical history, sexual and reproductive morbidity, treatment-seeking behavior, and the type, extent, and course of the disability. Verbatim responses of the participants were noted. Data were manually coded and collated into possible themes. Postpolio residual paralysis (80; 30.7%) was the main reported disability, followed by severe sight impairment (52; 19.9%). A majority (170; 65%) of participants were unmarried. Of them, 66 (39%) were not willing to get married. The prevalence of SRH problems was high (151; 57.9%) among WWD, and only 82 (54%) took treatment. Dysmenorrhea (47; 31.1%), irregular periods (36; 23.8%), and vaginal discharge (17; 11.3%) were the main problems reported. The WWD in this study were likely to hide their SRH problems from others out of shame or fear. Among WWD, the prevalence of SRH problems is high and obtaining relief is difficult.


A randomized control trial of a virtual reality learning environment in obstetric medical student teaching.
Virtual reality learning environments (VRLE) have the potential to transform the delivery of teaching in obstetrics. Medical students often find it difficult to conceptualize fetal lie and presentation. We conducted a single-centre randomized control trial of medical students using VRLE (n = 35) to depict fetal lie and presentation, compared with a control group (n = 34) using traditional 2-dimensional images. The VRLE, delivered using a mounted display headset, created an immersive experience exploring fetal lie and presentation. Clinical examination skills were then assessed using an obstetric abdominal model. The primary outcome was knowledge, as assessed by determination of fetal lie and presentation on an obstetric model. Secondary outcomes were time taken to successfully complete the task, and the student experience. There was a non-significant trend towards improved knowledge outcomes using the VRLE compared to traditional methods with 70 % (n = 23) in the VRLE group determining the correct fetal lie and presentation compared with 56 % (n = 19) in the control group (OR.551 CI 0.202-1.504, p = 0.242). Students in the intervention group more efficiently completed the task (45 s ± 12.95 vs 38 s ± 10.83 CI 1.701,13.367p = 0.012) and better enjoyed the virtual learning experience with student confidence and satisfaction scores significantly higher (p = 0.02). It is feasible to use VRLE to teach medical students clinical skills such as fetal lie and presentation, enhancing the learning experience in both student satisfaction and confidence, with positive trends towards improved knowledge outcomes demonstrated.


Does endogenous GLP-1 affect resting energy expenditure and fuel selection in overweight and obese adults?
To investigate the association between fasting glucagon-like peptide 1 (GLP-1) levels and resting energy expenditure (REE), and respiratory quotient (RQ) in overweight and obese adults. Study participants were enrolled at the Dietetic and Metabolic Unit, University of Pavia, Italy. Inclusion criteria were age ≥ 25 and ≤ 45 years, and body mass index (BMI) ≥ 25 and ≤ 35 kg/m2. Diabetic subjects were excluded. Body composition was measured by dual-energy X-ray absorptiometry. REE was evaluated using indirect calorimetry, and RQ was calculated from respiratory gas exchanges. Fasting GLP-1, glucose, insulin and free fatty acid (FFA) levels, and 24-h norepinephrine urinary excretion were measured. Homeostasis model assessments of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β) were calculated. Thirty-seven participants were included (age 43.4 ± 1.6 years; BMI 30.6 ± 0.5 kg/m2). REE was not associated with fasting GLP-1 levels (p = 0.98) after adjustment for age, sex, fat-free mass (FFM), and fat mass (FM). Similarly, no association was observed between RQ and GLP-1 levels (p = 0.95), after adjustment for age, sex, and body fat. In adults subjects with increased adiposity fasting, GLP-1 levels do not seem to play a role in the regulation of energy metabolism and in fuel selection.


Oral immunization with bacterial lysate against infection with Streptococcus pneumoniae in mice.
The protective effect of oral immunization against infection with Streptococcus pneumoniae was investigated in mice. Two bacterial lysates, one with an additional lysate of Candida albicans, were investigated. Intranasal inoculation of adult Balb-C mice with a S. pneumoniae type I strain resulted in a lethal infection, with deaths occurring from the 2nd until the 6th day after infection. Oral immunization resulted in a significant decrease in mortality rate (18-48% reduction). No significant difference in mortality rates was observed between the groups immunized with different lysates in the same concentrations.


Population-based study of esophageal and small intestinal atresia/stenosis.
The aim of this study was to describe the prevalence of esophageal atresia/stenosis and small intestinal atresia/stenosis in Nagano, Japan, together with associated anomalies, prenatal diagnosis and survival. A population-based cohort study of the prevalence of esophageal atresia/stenosis and small intestinal atresia/stenosis was conducted in Nagano in January 1993-December 2011. The Mann-Whitney test, χ(2) test and Kruskal-Wallis test were used to compare variables. P < 0.05 was considered statistically significant. In total, 74 cases of esophageal atresia/stenosis and 87 cases of small intestinal atresia/stenosis (31 duodenal, 56 jejuno-ileal) were identified. Prevalences were 1.97 for esophageal atresia/stenosis and 2.23 for small intestinal atresia/stenosis (0.83 for duodenal atresia/stenosis and 1.49 for jejuno-ileal atresia/stenosis) per 10,000 births, respectively. The prevalence of esophageal atresia/stenosis increased significantly from 1993-2001 to 2002-2011 (relative risk [RR], 1.6), as did the prevalences of duodenal atresia/stenosis (RR, 2.2) and jejuno-ileal atresia/stenosis (RR, 3.1). Chromosomal anomalies, particularly trisomy 21, were seen significantly more often in association with duodenal atresia/stenosis (55%) than with esophageal atresia/stenosis (28%, P < 0.01) or jejuno-ileal atresia/stenosis (2%, P < 0.01). The proportion of patients associated with prenatally diagnosed chromosomal anomaly was higher compared to postnatal diagnosis (P < 0.01) in the esophageal atresia/stenosis group. The prevalence of esophageal and small intestinal atresia/stenosis increased significantly from 1993-2001 to 2002-2011. Prenatally diagnosed esophageal atresia/stenosis is associated with multiple anomalies, particularly chromosomal anomalies, compared to other small intestine atresia/stenosis.


Pathologic features of familial visceral myopathy.
Familial visceral myopathy is the most common cause of chronic primary (idiopathic) intestinal pseudo-obstruction. We studied four family groups with this disease and found that it has a characteristic morphologic appearance. Grossly, there is segmental dilatation of the alimentary tract, often involving multiple sites and most commonly producing a megaduodenum. Microscopically, the involved areas show a characteristic change consisting of degenerating muscle cells and fibrosis, which may involve the full thickness of the muscularis propria but is often more prominent in or limited to the external layer. Degenerating muscle cells appear pale, poorly defined, and fragmented. As residual thread-like remnants become surrounded by collagen or as muscle cells are destroyed, leaving apparent spaces surrounded by collagen, the longitudinal and circular muscles take on a vacuolated appearance easily recognized at low magnifications. Recognition of this change is greatly facilitated by use of a trichrome stain, and mild lesions may be recognized only with such stains. The nondilated segments of intestine show similar changes but of a less severe degree. Neural and vascular structures are apparently normal. Although the lesion most closely resembles progressive systemic sclerosis, the degenerating muscle cells and vacuolated appearance of the muscle serve to distinguish familial visceral myopathy from the latter entity.


Conjunctivitis as a manifestation of Wegener's Granulomatosis.
To report a case of prolonged conjunctivitis as the manifestation of Granulomatosis with polyangiitis (GPA). A 37-year-old man presented with prolonged conjunctivitis which had persisted for one month. He was taking medication for his conjunctivitis without any response. A slit-lamp examination revealed conjunctivitis and scleritis in the right eye. Conjunctivitis, 360-degree peripheral corneal thinning, corneal perforation, and scleritis were seen in the left eye. Emergency penetrating keratoplasty was performed to treat the patient's corneal perforation. After a consultation with the Internal Medicine Department, the patient was suspected of having GPA with positive cytoplasmic anti-neutrophil cytoplasmic antibodies (C-ANCA). Functional endoscopic sinus surgery was performed to treat right maxillary sinusitis, and a biopsy of the maxillary sinus mucosa was obtained. The pathology report showed granuloma and vasculitis with severe acute and chronic inflammation and few eosinophils; thus, the diagnosis was confirmed. Because prolonged conjunctivitis occurs only rarely in association with systemic disease, ophthalmologists should be aware of this potential, particularly in patients with GPA.


A qualitative study of religious practices by chronic mentally ill and their caregivers in South India.
Socio-cultural explanatory factors for mental health problems determine help seeking behaviors. The study aimed to understand the reasons mentally ill patients and their families in India choose to seek help from a religious site. Persons with mental illness and their families were interviewed at religious sites using a guideline questionnaire. Issues such as significant life events, explanations for perceived abnormal behavior and reasons for choosing a specific religious site for 'treatment' were explored. Seeking religious help for mental disorders is often a first step in the management of mental disorders as a result of cultural explanations for the illness. This behavior also has social sanctions.


Determinants of periodontopathogens in microbiological monitoring of diabetic patients with periodontitis.
To determine and analyze the frequency of periodontopathogens in microbiological monitoring of diabetic patients with periodontitis. This cross-sectional study included 352 diabetic patients with periodontitis who were registered at Riyadh Armed Forces Hospital, King Faisal Specialist Hospital and Research Centre, King Abdul Aziz Medical City, Naval Base Hospital, and Sultan Bin Adulaziz Humanitarian City, Riyadh, Kingdom of Saudi Arabia from July 2004 to August 2008. Microbiological analysis comprised the detection of Bacteroides forsythus (Bf), Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Prevotella intermedia (Pi) by polymerase chain reaction method. The mean age of patients was 54.4 +/- 0.67 (range: 21-80 years). There were 214 (61%) males and 138 (39%) females. Among the study population, 36 (10%) had type 1, and 316 (90%) patients had type 2 diabetes. The results showed that 55.6% of patients had Bf, 51.7% had Aa, 63.7% had Pg, and 6.1% had Pi. The frequencies of periodontopathogens were higher in males than females in all age groups. The risk of periodontopathogens Bf were found higher level in 41-50 age group, Aa in 51-60, Pg in 51-60, and Pi in 31-40 age groups. This study found that the frequencies of periodontal pathogens Bf, Aa, and Pg were higher than Pi in diabetic patients with periodontitis.


Data on assessment and exploratory statistical correlation data analysis of sintered Nd:YAG laser welded 2507 duplex stainless steel.
The effect Spark Plasma Sintering (SPS) parameters and Nd:YAG laser welding parameters such as sintering temperature, sintering time, welding power, welding speed, on Vickers hardness mechanical properties of the Weld Zone(WZ) was statistically investigated. Rectangular plates of 2507 Duplex Stainless Steel (DSS) fabricated by SPS were joined by Nd: YAG laser welding process. Linear regression analysis was performed on the data, followed by Pearson correlation analysis to relate hardness with other predicting variables and show their statistical significance to hardness value of the weld zone.The evaluated R 2 which is 49%% was used to measure the closeness of the data to the regression fitted line.


Contributi scientifici in memoria di Antonio Fusco.
Come si leggerà nell'Introduzione della sezione propriamente scientifica del Volume, il presente testo nasce dalla volontà e, soprattutto, dall'esigenza culturale di omaggiare il fu Prof. Antonio Fusco. Un debito scientifico ed umano che trova il suo locus naturale in questa prima parte del testo stesso, cui farà poi seguito la parte propriamente scientifica. In siffatta parentesi dovuta per le ragioni appena menzionate, il lettore, l'amico o l'allievo dell'opera del Prof. Fusco potranno trovare un suo sintetico Curriculum Vitae, correlato da una specifica ed accurata prosa, svolta dal già Magnifico Rettore Carlo Cipolli; il quale, oltre che evidenziare, ricordando, i meriti del collega oramai scomparso, aggiunge alsuo scritto un elemento che sarebbe imprescindibile a non trasformare lo stesso in una mera sequenza di parole: l'amicizia e l'affetto per un amico che, oramai, non c'è più. A fine lettura, evidente risuonerà il fatto che la vita di ognuno, se mossa dalla passione per ciò per cui si è predisposti cognitivamente e psicologicamente, può essere ricca di riconoscimenti, riconoscenze e soddisfazioni che, lungi dal divenire un cuscino di allori su cui adagiarsi, per una mente creativa come quella del Prof. Fusco hanno funto solo da motivazioni ad agire instancabilmente guardando sempre al futuro. Il lavoro di una vita che, materialmente, è sancito da un supporto poco più di cm 25x15: una targa. Una materialità evidente che, con grande commozione e riconoscenza, è stata affissa il 25 ottobre 2019 sull'aula fronte l'Aula Magna del Campus "La Folcara", a testimonianza che quello spirito creativo in continua evoluzione non si ferma; non si arresta neppure con la fine biologica di chi lo ha "posseduto". Rimangono le opere ed il pensiero del Prof. Fusco e restano gli affetti. A tal proposito, il lettore troverà una breve e sentita sezione su Testimonianze; coloro i quali hanno avuto modo, nell'arco della vita accademica ed umana, personale, di Fusco di conoscerlo. Ecco, allora, che i ricordi saranno i veri protagonisti di questa parentesi. Dopo di ciò, prima dei contributi prettamente scientifici dei lavori, tenutisi in occasione del Convegno Internazionale Psicologia, Arte, Letteratura. Antiche e Nuove Tendenze, seguiranno i saluti delle autorità che in quei due giorni si sono succedute a rappresentare non solo l'istituzione affiliata, ma anche la relazione di stima e di affetto che le legava al compianto Professore. Si passerà, infine, al volume tradizionalmente inteso.


Motor cortex excitability in patients with focal epilepsy.
We studied the excitability of the motor cortex using, transcranial magnetic stimulation (TMS) in patients with temporal and extratemporal epilepsy. We applied single and paired-pulse TMS to 15 patients with temporal (n = 7), extratemporal (n = 6) and focal epilepsy lateralised to one hemisphere (n = 2). Patients had no antiepileptic drugs in the last 48 h and were seizure free for 4 h prior to testing. We determined the threshold for EMG responses at rest (RMT), the cortically evoked silent period (CSSP) and intracortical inhibition (ICI, intervals of 2-4 ms) and facilitation (ICF, 7-15 ms) and compared the results to those obtained in 17 normal controls. ICI and ICF was reduced in both hemispheres (P < 0.01. ANOVA) compared to the controls. In the hemisphere of seizure origin ('abnormal') there was a reduction of ICF (P < 0.01) and normal ICI, in the 'normal' hemisphere there was a reduced ICI (P < 0.01) and a slight reduction of ICF (P < 0.05). ICF on the 'abnormal' side was reduced (P < 0.05) compared to the 'normal' hemisphere. RMT was increased in two patients, but group comparison of RMT and CSSP showed no significant differences between patients and controls. The results suggest a remote effect of epileptic activity onto the motor cortex leading to an alteration of activity in local inhibitory circuits.


Nanocarriers for effective delivery: modulation of innate immunity for the management of infections and the associated complications.
Innate immunity is the first line of defense against invading pathogens. Innate immune cells can recognize invading pathogens through recognizing pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). The recognition of PAMPs by PRRs triggers immune defense mechanisms and the secretion of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. However, sustained and overwhelming activation of immune system may disrupt immune homeostasis and contribute to inflammatory disorders. Immunomodulators targeting PRRs may be beneficial to treat infectious diseases and their associated complications. However, therapeutic performances of immunomodulators can be negatively affected by (1) high immune-mediated toxicity, (2) poor solubility and (3) bioactivity loss after long circulation. Recently, nanocarriers have emerged as a very promising tool to overcome these obstacles owning to their unique properties such as sustained circulation, desired bio-distribution, and preferred pharmacokinetic and pharmacodynamic profiles. In this review, we aim to provide an up-to-date overview on the strategies and applications of nanocarrier-assisted innate immune modulation for the management of infections and their associated complications. We first summarize examples of important innate immune modulators. The types of nanomaterials available for drug delivery, as well as their applications for the delivery of immunomodulatory drugs and vaccine adjuvants are also discussed.


Revascularization and healing of onlay particulate allogeneic bone grafts in primates.
Particle size of allogeneic bone grafts was investigated to determine its effect on revascularization and healing. Freeze-dried chips of different sizes were placed on the monkey lateral mandibular cortex, and the subsequent healing and revascularization were studied by histologic, autoradiographic, and microangiographic techniques. It appears that allogeneic bone is a reasonable substitute for autologous bone in mandibular ridge augmentation procedures.


Localization of smg p25A/rab3A p25, a small GTP-binding protein, at the active zone of the rat neuromuscular junction.
smg p25A is a small G protein which has been suggested to regulate neurotransmitter release from the synapses. We investigated here the ultrastructural localization of this small G protein in the rat neuromuscular junction by an immunoperoxidase method. The results showed that smg p25A was distributed non-uniformly on the presynaptic plasma membrane and among the synaptic vesicles with the focal accumulation on the discrete presynaptic sites which corresponded to the active zones, the regions of the presynaptic plasma membrane specialized for the exocytosis of the synaptic vesicles. This unique distribution of smg p25A suggests that it plays an important role in the attachment and fusion of the synaptic vesicles with the active zones.


Mechanism of PbI2 in Situ Passivated Perovskite Films for Enhancing the Performance of Perovskite Solar Cells.
Perovskite solar cells (PSCs) have gained tremendous research interest because of their tolerance of defects, low cost, and facile processing. In PSC devices, PbI2 has been utilized to passivate defects at perovskite film surfaces and GBs; however, a systematic mechanism of PbI2 in situ passivation for enhancing the solar cells efficiency has not been fully explored. Here, this work, we systematically studies the effect of the precise PbI2 ratio and the PbI2 in situ passivation mechanism based on trap density, carrier lifetime, Fermi level, and so forth. This study finds the appropriate ratio of I/Pb to be around 2.57:1 using energy-dispersive spectroscopy. After the moderate excess PbI2 in situ passivation, the trap density is reduced from 6.12 × 1016 to 3.38 × 1016 cm-3, and the carrier lifetime is extended from 168.35 to 368.77 ps by using fs-TA spectroscopy. This result indicates that the moderate excess PbI2 in situ passivation can reduce the trap density and suppress the nonradiative recombination. The efficiency of solar cell has shown a nearly 11.3% improvement of 19.55% for an I/Pb ratio of 2.57:1 compared with 2.69:1. It also demonstrates that the efficiency of PSCs can be enhanced effectively by PbI2 in situ passivation.


Pregnancy-associated plasma protein A (PAPP-A) specifically inhibits the third component of human complement (C3).
Pregnancy-associated plasma protein A (PAPP-A), a macromolecular glycoprotein associated with pregnancy, was shown to inhibit complement-induced haemolysis and to bind heparin reversibly. Because of the inhibitory effects of heparin on the complement cascade it was not clear if the inhibition of complement activity observed with PAPP-A (isolated from heparin plasma) was attributable to the heparin moiety bound to PAPP-A. This work demonstrates that heparin exerts an inhibitory effect on complement activity but that heparin-free PAPP-A is also inhibitory. PAPP-A specifically inhibits C3 by binding to this complement subcomponent and not by inhibiting C3 convertase as demonstrated for C3 inactivator.


Anterior knee pain.
Anterior knee pain is a common symptom, especially in adolescence, and often no specific cause is sought or identified. Physicians who treat patients with knee pain should understand the normal anatomic features and the biomechanics of the patellofemoral joint. We review this information and discuss important aspects of the physical examination and roentgenographic evaluation in patients with anterior knee pain. Once the clinical cause of anterior knee pain has been established, directed nonoperative treatment including physical therapy should be initiated. Surgical intervention is generally reserved for patients in whom nonoperative management is unsuccessful and identifiable abnormalities exist.


Optimal Trend Tests for Genetic Association Studies of Heterogeneous Diseases.
The Cochran-Armitage trend test is a standard procedure in genetic association studies. It is a directed test with high power to detect genetic effects that follow the gene-dosage model. In this paper, the author proposes optimal trend tests for genetic association studies of heterogeneous diseases. Monte-Carlo simulations show that the power gain of the optimal trend tests over the conventional Cochran-Armitage trend test is striking when the genetic effects are heterogeneous. The easy-to-use R 3.1.2 software (R Foundation for Statistical Computing, Vienna, Austria) code is provided. The optimal trend tests are recommended for routine use.


gamma-Hexachlorocyclohexane stimulation of macrophage phospholipid hydrolysis and leukotriene production.
gamma-Hexachlorocyclohexane stimulates arachidonic acid release from macrophage phospholipids. It is also a powerful stimulator of leukotriene C4 production, yet (by comparison with zymosan) produces only a small effect on prostaglandin production. This suggests that synthesis of leukotrienes and prostaglandins can be independently regulated. The most likely mechanism of action of gamma-hexachlorocyclohexane is through its effect on phosphatidylinositol metabolism.


Sulfated modification of the water-soluble polysaccharides from Polyporus albicans mycelia and its potential biological activities.
In this study, three chemically sulfated polysaccharides (SPAPs) were derived from one water-soluble polysaccharide (PAP) of Polyporus albicans mycelia by chlorosulfonic acid-pyridine method. The effects of polysaccharides on the immune function were examined after the mice were intragastrical administrated with polysaccharides at three doses of 100, 200, and 300 mg/kg body weight for 7 days. The results showed that both the lymphocytes proliferation and macrophage function were significantly enhanced by SPAP in all groups along with the increase of the substitution degree and dose (P<0.01). It indicated that SPAP could be a potential immunostimulants used in the food and pharmaceutical industry.


Adhesion and growth of rat aortic smooth muscle cells on lactide-based polymers.
Biodegradable materials based on polymers of hydroxy acids are studied for application in artificial vascular substitutes. Polymers with functional surfaces are being developed, carrying specific recognition structures to affect selectively the adhesion and proliferation of endothelial cells (EC) and vascular smooth muscle cells (VSMC). This preliminary study focuses on evaluation of adhesion and growth of VSMC on surfaces of polylactide polymers and those modified by amphiphilic polylactide/poly(ethylene oxide) copolymers. Poly(L-lactic acid), PLLA, and poly(DL-lactic acid), PDLLA, and a block copolymer of lactide with a carboxylated poly(ethylene oxide) segment, PLLA-b-PEO-COOH, were synthesized by controlled polymerization of L and D,L-lactide, respectively, and using delta-hydroxy-Z-carboxymethyl-PEO as a macroinitiator for the copolymer. Films of polymers were deposited on glass coverslips by a spin-coating method. Uncoated glass coverslips and Falcon dishes were used as control substrates. VSMC were obtained from the thoracic aorta of young adult male Wistar rats by explantation method and seeded in Dulbecco-Modified Eagle MEM with 10% foetal bovine serum. The number of adhering cells, their shape, size of cell-material contact area and cell population doubling time were evaluated from day 1 to 7 after seeding. It was found that both PLLA and especially PDLLA relatively well supported adhesion and growth of VSMC. However, on carboxylated surfaces of the PLLA-b-PEO-COOH copolymer, a lower number of initially adhering cells (by 37% than on Falcon dishes, pdelta0.05), smaller cell spreading area (by 45% and 37% than on glass and Falcon dishes, respectively, pdelta0.01) and longer doubling time (by 49% and 31% than on glass and Falcon dishes, pdelta0.001). Thus, surfaces coated by a PLA/PEO-COOH copolymer can be used as minimum background surface to reveal the effect of other more specific adhesion structures.


New Findings in Early-Stage Keratoconus: Lamina Cribrosa Curvature, Retinal Nerve Fiber Layer Thickness, and Vascular Perfusion.
Our aim was to investigate the involvement of posterior pole structures in eyes affected by keratoconus (KC). Optical coherence tomography (OCT) and OCT angiography (OCTA) were used to determine the status of lamina cribrosa (LC), peripapillary retinal nerve fiber layer (RNFL), macular and peripapillary microvasculature. Observational, cross-sectional, case-control analysis. Single-center investigation involving patients with KC and healthy control subjects. Enrolled subjects underwent anterior segment OCT combined with Placido-disk topography, macular and optic nerve head swept-source OCT and swept-source OCTA scans, and 3D wide glaucoma module for peripapillary RNFL thickness measurement. The LC curvature index was used to express the degree of LC posterior bowing. We calculated the vessel density and vessel length density at the macular superficial capillary plexus, deep capillary plexus, choriocapillaris, and nerve radial peripapillary capillary plexus. Overall, 32 eyes with KC and an equal number of age- and axial length-matched control eyes were included in the analysis. Almost all (97%) of eyes with KC were classified as early stage. KC displayed a reduction in peripapillary RNFL thickness (104.8 ± 11.9 µm vs 110.7 ± 10.5 µm; P = .039) and nerve radial peripapillary capillary plexus vessel density (46.31% ± 3% vs 43.82% ± 4%; P = .006) when compared with control subjects; these differences were more evident in the temporal sector and were associated with a higher LC curvature index (9.9% ± 2.6% vs 8.48% ± 1.7%; P = .012). Mean macular superficial capillary plexus vessel density was 3 percentage points lower in eyes with KC than in healthy controls (P < .001). Early-stage KC may be characterized by a posterior bowing of the LC along with a subtle peripapillary RNFL thinning and vascular impairment. These findings support the hypothesis that KC may be a corneal manifestation of a more generalized "eye collagen disease."


Interaction of rabbit muscle enolase and 3-phosphoglycerate mutase studied by ELISA and by batch gel filtration.
The interaction of rabbit skeletal muscle enolase and 3-phosphoglycerate mutase was detected by an ELISA test, a batch gel-filtration technique, and fluorescence anisotropy measurements, and the activity of enolase was determined to be a function of mutase concentration. The apparent dissociation constant of this enzyme complex is approximately 1 microM. This value seems to be independent of the presence (in fluorescence anisotropy measurements) or the absence (in activity as well as in ELISA experiments) of fluorescein isothiocyanate used widely as a label for determining the complex formation between enzymes in fluorescence anisotropy measurements.


Does pneumatic dilatation affect the outcome of laparoscopic cardiomyotomy?
Controversy surrounds the choice of laparoscopic cardiomyotomy as the primary treatment for achalasia or a second-line treatment following the failure of nonsurgical treatment. Laparoscopic cardiomyotomy can be more difficult technically following pneumatic dilatations. The aim of this study was to compare the outcome obtained with primary laparoscopic cardiomyotomy to that achieved when the procedure is performed following failed pneumatic dilatation. Laparoscopic cardiomyotomy was performed in seven patients following a median of four pneumatic dilatations (group A) and in five patients as their primary treatment (group B). Outcome was measured using manometry, a modified DeMeester symptom scoring system, and a quality-of-life questionnaire. There were no significant differences between groups A and B in sex, age, preoperative modified DeMeester score, or mean barrier pressure. Six of seven group A patients had evidence of periesophageal and submucosal fibrosis at surgery, but this condition was not seen in group B patients. The operative time was slightly longer in group A patients. There was no difference in complication rates (one primary hemorrhage in group A and one esophageal perforation in group B), and both groups had a significantly improved modified DeMeester score at 6 weeks and at long-term follow-up (median, 26 months). Eleven of 12 patients said that they would choose laparoscopic cardiomyotomy as their primary treatment if newly diagnosed with achalasia. Laparoscopic cardiomyotomy is safe and effective as a primary or second-line treatment following pneumatic dilatations in patients with achalasia.


Association of serum lipid levels and prostate cancer severity among Hispanic Puerto Rican men.
While obesity and fat intake have been associated with an increased risk of prostate cancer (PCa) aggressiveness and mortality, the association between lipid levels and PCa phenotype remains unclear. Previous reports evaluating this association are inconsistent and highly variable when considering different racial/ethnic groups. There are scarce data regarding this association among Hispanics, and specifically Puerto Rico's Hispanic men, a population with a higher burden of PCa, metabolic syndrome and overweight. This population has a different ancestry profile than other Hispanics from Central and South America. Due to the above the researchers inquired if there is a relationship between serum lipid levels and PCa phenotype in this understudied population using a cohort of patients treated with radical prostatectomy as their first treatment. We performed an exploratory retrospective medical record review study of 199 PCa patients who underwent radical prostatectomy between 2005 and 2012. Variables analyzed included age at PCa diagnosis, Body Mass Index (BMI), preoperative serum prostate-specific antigen (PSA), lipid levels, and clinical parameters such as prostatectomy pathologic stage and Gleason Score (GS). PCa severity was defined using pathologic stage and GS. Unadjusted and adjusted logistic regression models were fitted to estimate the odds ratios (ORs) with 95 % confidence intervals (CI) to define the relationship among clinical characteristics and PCa severity. Mean age for the cohort was 58.8 years (range: 40-75), 78.9 % were overweight or obese, 36.7 % had hypertriglyceridemia, and 35.2 % had low HDL levels. In the unadjusted logistic regression model, hypertriglyceridemia (OR: 2.11, 95 % CI = 1.13-3.93), low HDL (OR: 1.90, 95 % CI = 1.02-3.56-), and age (OR: 2.34, 95 % CI 1.25-4.40) were significantly associated with a diagnosis of high severity of PCa. In Puerto Rican men with PCa, elevated hypertriglyceridemia, low HDL levels, and age were statistically associated with high grade PCa on bivariate analysis. Total cholesterol level was not associated with severity of disease. Associations lost significance upon multivariate adjustment. These data generate important hypotheses regarding the potential relationship between lipid pathways and PCa development and underscore the need to perform larger scale and longitudinal studies to sort out whether, hypertriglyceridemia is associated with PCa phenotype and development.


Comparative analysis of immunization schedules using a novel adenovirus-based immunotherapeutic targeting hepatitis B in naïve and tolerant mouse models.
Development of active targeted immunotherapeutics is a rapid developing field in the arena of chronic infectious diseases. The question of repeated, closely spaced administration of immunotherapeutics to achieve a rapid impact on the replicating agent is an important one. We analyzed here, using a prototype adenovirus-based immunotherapeutic encoding Core and Polymerase from the hepatitis B virus (Ad-HBV), the influence of closely spaced repeated immunizations on the level and quality of induced HBV-specific and vector-specific immune responses in various mouse models. Ad-HBV, whether injected once or multiple times, was able to induce HBV- and adeno-specific T cells both in HBV-free mice and in a HBV tolerant mouse model. Adenovirus-specific T cell responses and titers of neutralizing anti-Ad5 antibodies increased from time of the 3rd injection. Interestingly, single or multiple Ad-HBV injections resulted in detection of Polymerase-specific functional T cells in HBV tolerant mice. Overall no modulation of the levels of HBV-specific cytokine-producing (IFNγ/TNFα) and cytolytic T cells was observed following repeated administrations (3 or 6 weekly injections) when compared with levels detected after a single injection with the exception of two markers: 1. the proportion of HBV-specific IFNγ-producing cells bearing the CD27+/CD43+ phenotype appeared to be sustained in C57BL/6J mice following 6 weekly injections; 2. the percentage of IFNγ/TNFα Core-specific producing cells observed in spleens of HLA-A2 mice as well as of that specific of Polymerase observed in livers of HBV tolerant mice was maintained. In addition, percentage of HBV-specific T cells expressing PD-1 was not increased by multiple injections. Overall these data show that, under experimental conditions used, rapid, closely spaced administrations of an adenovirus-based HBV immunotherapeutics does not inhibit induced T-cell responses including in a HBV-tolerant environment.


Development and Evaluation of a Mobile Web-based Food Allergy and Anaphylaxis Management Educational Program for Parents of School-aged Children with Food Allergy: A Randomized Controlled Trial.
This study aimed to develop a mobile web-based food allergy (FA) and anaphylaxis management educational program for parents of school-aged children with food allergies and evaluate its effectiveness. A mobile program was developed based on a web-based teaching-learning system model. Its effectiveness was subsequently evaluated using a parallel, randomized controlled pre- and post-test design. This study included 73 parents of school-aged children with food allergies. These parents were randomly assigned to either the experimental (n = 37) or control (n = 36) groups. The experimental group participated in a 2-week mobile web-based educational program that covered major topics in FA and anaphylaxis management. These topics included an understanding of food allergies and anaphylaxis, learning techniques for using an epinephrine auto-injector, and developing an emergency action plan. An educational booklet was provided to the control group. Participants completed a pre-test and two post-test questionnaires to evaluate the impact of the program. The assessment tools were the Food Allergy Knowledge Test, Food Allergy Self-Efficacy for Parents, and Food Management and Adaptation Scale. The data were analyzed using descriptive statistics, a test of homogeneity for the pre-test, an independent t-test, and repeated measures ANOVA. The experimental group experienced greater improvement in the knowledge of FA (post-intervention t = 14.51, p < .001; 2 weeks post-intervention, t = 16.15, p < .001), FA self-efficacy (post-intervention t = 77.99, p < .001; 2 weeks post-intervention, t = 76.09, p < .001), and practice behavior in FA management (post-intervention t = 28.10, p < .001; 2 weeks post-intervention, t = 27.98, p < .001) after web-based FA education. This study revealed improvements in the knowledge, self-efficacy, and practice behaviors of parents regarding FA and anaphylaxis management. Therefore, the mobile web-based educational program can contribute to the effective management of food allergies and anaphylaxis for parents of school-aged children. CRIS registration: KCT0007491.


Benzothieno and benzofurano annelated estranes.
The preparation of estrone derived benzothieno- and benzofurano fused steroids is described. Keystep is an intramolecular thienyl(/furyl)-ene-yne cyclization of 16-ethynyl-17-heterarylestra-1,3,5(10),16-tetraenes. The cyclization was carried out under Pt as well as under Ru catalysis.


The impact of HIRAID on emergency nurses' self-efficacy, anxiety and perceived control: A simulated study.
Emergency nurses must perform accurate and complete comprehensive patient assessments to establish patient treatment needs and expedite care. To evaluate the impact of a structured approach to emergency nursing assessment following triage, on novice emergency nurses' anxiety, self-efficacy and perceptions of control. Thirty eight early career emergency nurses from five Australian hospitals performed an initial patient assessment in an immersive clinical simulated scenario, before and after undertaking training in HIRAID, an evidence-informed patient assessment framework for emergency nurses. Immediately following each scenario the nurses completed a questionnaire scoring anxiety, self-efficacy and perceptions of control levels. Paired sample t-tests and effect sizes were calculated. Participant anxiety levels were lower after HIRAID training compared to before undertaking the training (Mean (SD) = 53.26 (10.76) vs 47.46 (9.96), P = 0.002). Self-efficacy levels in assessment performance increased (189.32 (66.48) vs 214.06 (51.35), P = 0.001). There was no change in perceptions of control (31.24 (7.38) vs 30.98 (8.38), P = 0.829). High levels of anxiety and low levels of self-efficacy are known to be negatively correlated with clinical reasoning skills and performance. The effect of HIRAID training on reducing anxiety and increasing self-efficacy has the potential to improve emergency nurses' assessment performance and the quality and safety of patient care.


Inhibition of human activated Factor X by antithrombin III and alpha 1-proteinase inhibitor in human plasma.
The inhibition of activated human Factor X by human plasma protease inhibitors was investigated in both purified and plasma systems. In the former, antithrombin III, alpha 1-proteinase inhibitor, and alpha 2-macroglobulin, at normal plasma concentrations, markedly inhibited activated Factor X. Significant inhibition by alpha 2-antiplasmin, however, was only achieved when present at 40 times its plasma concentration. The relative rates of inhibition of activated Factor X coagulant activity in normal human plasma, antithrombin III-deficient plasma, and alpha 1-proteinase inhibitor-deficient plasma were 1.0, 0.63, and 0.75, respectively. From these relative rates of inhibition and their measured concentrations in the 3 plasmas, it was calculated that antithrombin III, alpha 1-proteinase inhibitor, and alpha 2-macroglobulin contribute 53, 35, and 12%, respectively, to the inhibition of activated Factor X in normal human plasma. Using 125I-labeled activated Factor X and a combination of sodium dodecyl sulfate disc gel electrophoresis and immunoadsorption, it was then demonstrated that antithrombin III accounted for 45-55%, alpha 1-proteinase inhibitor, 35-40%, and alpha 2-macroglobulin, 10-15% of the inhibition of the labeled protease in normal human plasma. The values obtained with the deficient plasmas are consistent with the distribution of activated Factor X-inhibitor complexes in normal human plasma. These data show by two independent techniques, one measuring coagulant activity and the other 125I-labeled activated Factor X-inhibitor complexes, that both antithrombin III and alpha 1-proteinase inhibitor are the major inhibitors of activated Factor X in normal human plasma.


Identification and estimation of cell types in mixed primary cell cultures of early and term human placenta.
Placental villi of early and term human placentae were dissociated with trypsin and mixed cell cultures were established. The different cell types were identified and estimated over a 14-day culture period using antibodies to keratin and vimentin filaments and their capacity to phagocytose yeast. The three main cell types were found to be epithelial-, macrophage- and fibroblast-like cells. The epithelial-like cells can be further divided into the multinucleated and the small- and medium-sized round cells, and these are most likely to be derived from the trophoblast. The cellular composition of cultures were different for early and term placentae and also varied characteristically over the 14-day cultures period.


Through-space control of the persistence of photogenerated o-quinonoid intermediates in naphthalenes containing cofacially oriented chromenes and arenes.
Remarkable modulation of the persistence of the photogenerated colored o-quinonoid intermediates via a through-space interaction has been demonstrated in chromenes 1-4 based on 1,8-diarylnaphthalenes. Polar/π interaction is shown to stabilize the closed form of 4 to such an extent that photoinduced coloration is virtually invisible, while the same stabilization in the opened form of 2 permits ready coloration with a long-lived o-quinonoid intermediate.


Purple urine bag syndrome.
The purple urine bag syndrome (PUBS) is a rare condition associated with chronic urinary catheterization. It is characterized by the purple discoloration of the urine, collecting bag, and tubing. A number of factors are involved, but not always present, in its development including female sex, urinary tract infection, constipation, indicanuria, and alkaline urine. Despite multiple theories that involve the complex tryptophan metabolism to the tubing dye, the cause remains elusive. The syndrome resolves usually after treatment of urinary tract infection or changing of the collecting bag. We present a case of a patient with purple urine bag syndrome and a pertinent literature review.


Design, synthesis, and evaluation of salicyladimine derivatives as multitarget-directed ligands against Alzheimer's disease.
A series of salicyladimine derivatives were designed, synthesized and evaluated as multi-target-directed ligands for the treatment of Alzheimer's disease (AD). Biological activity results demonstrated that some derivatives possessed significant inhibitory activities against amyloid-β (Aβ) aggregation and human monoamine oxidase B (hMAO-B) as well as remarkable antioxidant effects and low cell toxicity. The optimal compound, 5, exhibited excellent potency for inhibition of self-induced Aβ1-42 aggregation (91.3±2.1%, 25μM), inhibition of hMAO-B (IC50, 1.73±0.39μM), antioxidant effects (43.4±2.6μM of IC50 by DPPH method, 0.67±0.06 trolox equivalent by ABTS method), metal chelation and BBB penetration. Furthermore, compound 5 had neuroprotective effects against ROS generation, H2O2-induced apoptosis, 6-OHDA-induced cell injury, and a significant in vitro anti-inflammatory activity. Collectively, these findings highlighted that compound 5 was a potential balanced multifunctional neuroprotective agent for the development of anti-AD drugs.


E-cigarette or vaping product use-associated lung injury: A great COVID-19 mimicker in young adult.
EVALI and COVID-19 share similar clinical and imaging features. Assessing the vaping or e-cigarette use history and conducting urine toxicology tests for high-risk patients are important with increasing COVID-19 cases in young adults.


Effects of a combined thermochemotherapy on markers of apoptosis, differentiation and adhesion in the human mammary carcinoma MX-1. A light microscopic and immunohistochemical study.
The susceptibility to apoptotic stimuli, the degree of differentiation and the adhesive properties are important determinants of a tumor's biological behavior and of the possibility of it's being influenced by treatment. In this study we examined the effects of a combined thermochemotherapy, consisting of the administration of the alkylating agents ifosfamide or mafosfamide combined with hyperthermia at 41 degrees C for one hour, applied to the human mammary carcinoma MX-1. We concentrated our observations on the apoptosis-associated proteins bax and bcl-2, on cytokeratin and vimentin as markers of differentiation, on desmosomes and on the antiadhesive epithelial membrane antigen episialin. These proteins were visualized immunohistochemically in cultured cells in vitro as well as in xenotransplants growing in nude mice in vivo. We found that the susceptibility of the surviving cells to apoptotic stimuli, measured by the bax/bcl-2 ratio, was much higher after a combined thermochemotherapy than after chemotherapy or thermotherapy alone. Many of these cells could probably be forced into apoptosis by later applying another kind of anticancer therapy. With regard to the expression of episialin after thermochemotherapy, fewer cells possessed an antiadhesive and, therefore, potentially invasive capacity. The number of desmosomes seemed not to be affected. As to their higher expression of cytokeratin and their unchanged expression of vimentin, the surviving cells appear to be more differentiated. Since these results could be observed in vivo as well as in vitro, it seems likely that, apart from its influence on the perfusion of the tumor, the amplification of the cytostatic efficacy of the chemotherapy by hyperthermia must be mediated by a direct mechanism.


Hereditary motor-sensory, motor, and sensory neuropathies in childhood.
Hereditary neuropathies (HN) are categorized according to clinical presentation, pathogenic mechanism based on electrophysiology, genetic transmission, age of occurrence, and, in selected cases, pathological findings. The combination of these parameters frequently orients towards specific genetic disorders. Ruling out a neuropathy secondary to a generalized metabolic disorder remains the first pediatric concern. Primary, motor-sensory are the most frequent HN and are dominated by demyelinating AD forms (CMT1). Others are demyelinating AR forms, axonal AD/AR forms, and forms with "intermediate" electrophysiological phenotype. Pure motor HN represent<10% of HN but exhibit large clinical and genetic heterogeneity. Sensory/dysautonomic HN cover five classical subtypes, each one related to specific genes. However, genetic heterogeneity is largly greater than initially suspected. Syndromic HN distinguish: "purely neurological syndromes", which are multisystemic, usually AD disorders, such as spinocerebellar atrophies +, spastic paraplegias +, etc. Peripheral Neuropathy may be the presenting feature, including in childhood. Clearly degenerative, AR forms prompt to investigate a large set of pleiotropic genes. Other syndromes, expressed in the perinatal period and comprising malformative features, are mainly developmental disorders, sometimes related to specific transcription factors. Altogether, >40 genes with various biological functions have been found responsible for HN. Many are responsible for various phenotypes, including some without the polyneuropathic trait: for the pediatric neurologist, phenotype/genotype correlations constitute a permanent bidirectional exercise.


cGMP modulates Arabidopsis lateral root formation through regulation of polar auxin transport.
The phytohormone auxin participates in lateral root formation and primary root growth in plants. The auxin gradient formation is mainly regulated by the direction of polar auxin transport (PAT). PAT requires PIN family proteins, which are auxin transport facilitators and contribute to the establishment and maintenance of auxin gradients and mediate multiple developmental processes. Here, we report the effect of the 3', 5'-cyclic guanosine monophosphate (cGMP), an important second messenger, on postembryonic developmental of Arabidopsis lateral root. We find that enhanced cGMP level through the application of the membrane permeable cGMP analog 8-Br-cGMP, promotes the initiation of lateral root primordia and formation of lateral root. 6-Anilino-5,8-quinolinedione (Ly83583, the guanylate cyclase inhibitor) negatively regulates the process. cGMP also mediates acropetal auxin transport and basipetal auxin transport in the root. We further find that 8-Br-cGMP and Ly83583 change the expression of auxin transport genes and alter the polar localization and expression of PIN1 and PIN2 proteins. Moreover, Ly83583 affects actin organization and localization. Taken together, we propose that cGMP affects auxin transport and auxin gradient through modulation PINs proteins localization and expression. cGMP regulates postembryonic formation of Arabidopsis lateral root through the crosstalk with PAT.


TORP ossiculoplasty in the presence of an intact stapes superstructure.
In this series, we describe ossicular reconstruction using routine TORP in the presence of the stapes superstructure using a tympanic-membrane-to-footplate configuration. This is a case series of 12 patients who underwent TORP ossiculoplasties from 1st January 2010 to 31st October 2017. Data collected included demographics, indication for surgery, status of the middle ear and pre-operative and post-operative audiometric data (including pure tone average (PTA) and air-bone gap (ABG)). The mean pre-operative PTA was 56.5 dB and ABG was 39.8 dB. Surgical success (ABG ≤ 20 dB) was achieved in 83.3%, with an average improvement in PTA of 24.3 dB and closure of ABG of 27.1 dB. The mean post-operative ABG was 12.7 dB. TORP ossiculoplasty with tympanic-membrane-to-footplate configuration is a feasible means of ossicular reconstruction, independent of the status or spatial arrangement of the remnant ossicles. Using this technique, it is possible to achieve a consistently good outcome for improvement in hearing and closure of ABG.


Joint pains with psoriasis and long-term systemic etretinate therapy: a case report and summary of 12 cases.
We report a case of psoriasis with joint pain related to long-term etretinate therapy. In addition, our experiences with twelve additional patients with psoriasis who also received etretinate therapy are discussed.


Application of recombinant DNA techniques in the development of viral vaccines.
The wide repertoire of methods developed for the construction and manipulation of recombinant DNA molecules enable viral genomes to be cloned and their genes expressed, in whole or in part, in microbial or animal cells in culture. This provides a ready source of many viral components that are otherwise difficult to obtain and in some cases were previously unknown. Although immediate applications for vaccine development have concentrated principally upon envelope proteins, the immunological importance of other viral components is being increasingly recognized. Hepatitis B virus is used here to exemplify the application of recombinant DNA technology to the development of subunit vaccines and to illustrate their value in studies of other viral proteins with particular emphasis on the role of the core antigen in providing protection against viral infection and hence its potential in vaccine development.


[Nephroblastoma and whole-body hemihypertrophy. Relation to Wiedemann-Beckwith's syndrome].
A child with hemihypertrophy presented with Wilm's tumor at 3 years of age. History included neonatal hypoglycemia and the discovery of hepatomegaly and renal dysplasia. This case report emphasizes the close relation of body hemihypertrophy to Beckwith's syndrome, as well as the high degree to which both predispose to certain tumors.


LINC00657 expedites neuropathic pain development by modulating miR-136/ZEB1 axis in a rat model.
Long non-coding RNAs (lncRNAs) are involved in the progression of several diseases. The interactions among lncRNAs, microRNA (miRNAs) or their targeting genes are reported to play crucial roles in the development of diseases. LINC00657 is observed to be upregulated in several cancers. However, the biological role of LINC00657 in neuropathic pain progress is unclear. Hence, in our study, we aimed to investigate the function of LINC00657 in neuropathic pain development. A chronic constriction injury (CCI) rat model was established, and we found that LINC00657 was greatly increased in CCI rats associated with a decrease of miR-136. Inhibition of LINC00657 suppressed neuropathic pain via alleviating mechanical and thermal hyperalgesia. In addition, miR-136 overexpression can also inhibit the neuropathic pain development. MiR-136 was predicted to serve as a miRNA target of LINC00657, and dual-luciferase reporter assay confirmed the correlation between LINC00657 and miR-136. Moreover, we observed that the decrease of LINC00657 was able to inhibit the neuroinflammation of CCI rats by targeting expression of cyclooxygenase-2, tumor necrosis factor-α and interleukin-1β while miR-136 inhibitors reversed this phenomenon. Next, by using bioinformatics analysis, ZEB1 was predicted as a direct target of miR-136, and miR-136 could negatively modulate ZEB1 expression. Besides these, ZEB1 was remarkably increased in the CCI rats. Knockdown of ZEB1 can inhibit neuropathic pain development, while miR-136 inhibitors can reverse it. In conclusion, it was implied that LINC00657 can induce the neuropathic pain development via regulating miR-136/ZEB1 axis.


Type II Cytokines Fine-Tune Thymic T Cell Selection to Offset Murine Central Nervous System Autoimmunity.
Early thymic progenitors (ETPs) are bone marrow-derived hematopoietic stem cells that remain multipotent and give rise to a variety of lineage-specific cells. Recently, we discovered a subset of murine ETPs that expresses the IL-4Rα/IL-13Rα1 heteroreceptor (HR) and commits only to the myeloid lineage. This is because IL-4/IL-13 signaling through the HR inhibits their T cell potential and enacts commitment of HR+ETPs to thymic resident CD11c+CD8α+ dendritic cells (DCs). In this study, we discovered that HR+-ETP-derived DCs function as APCs in the thymus and promote deletion of myelin-reactive T cells. Furthermore, this negative T cell selection function of HR+-ETP-derived DCs sustains protection against experimental allergic encephalomyelitis, a mouse model for human multiple sclerosis. These findings, while shedding light on the intricacies underlying ETP lineage commitment, reveal a novel, to our knowledge, function by which IL-4 and IL-13 cytokines condition thymic microenvironment to rheostat T cell selection and fine-tune central tolerance.


Small-conductance, Ca2+-activated K+ channel SK3 generates age-related memory and LTP deficits.
Cognitive deficits are among the most devastating changes associated with the aging process. Age-related decrement in performance on learning tasks is correlated with substantial changes in neuronal signal processing in the hippocampus. Here we show that elevated expression of small-conductance Ca2+-activated K+ channels (SK channels) of the SK3 type in hippocampi of aged mice contributes to reduced long-term potentiation (LTP) and impaired trace fear conditioning, a hippocampus-dependent learning task.


Thyroidectomy for Graves' hyperthyroidism. Retrospective study of patients' appreciation.
To retrospectively investigate the patients' views of surgical treatment of Graves' hyperthyroidism. One hundred two patients were included in the study and submitted to extensive subtotal thyroidectomy or total thyroidectomy between 1993-2003. Data were acquired from the responses to a questionnaire, that was completed by 83 patients. Before the operation the working/studying ability and the social/emotional relations were impaired in 20% and 22% of cases. Preoperative information was adequate for 84% of patients. The perception of the hospital efficiency was favourable in 89% of cases, and the interpersonal relations with clinicians and nurses were very positive for 96% of patients. After the operation, all patients were hypothyroid on levothyroxine (l-T4); unexpected problems with l-T4 therapy occurred in 6% of cases. Voice changes or neck discomfort were reported by 29% and 8% of patients. The aesthetic appearance of the scar was very satisfactory for 70% of patients, but 11% were unsatisfied. The working/studying ability and the social/emotional relations improved in 63% and 59% of cases. Eye symptoms improved in 71% of the patients with endocrine ophthalmopathy, but got worse in 60%. The quality of life, expressed with a 0 to 10 scale, improved from a mean preoperative score of 4.7 to a mean score of 7.9 (P = 0.000). Only 5% of patients expressed hesitation to recommend surgery to a friend with similar disease. Surgery is an effective therapy for selected cases of Graves' disease and meets the expectations of the majority of patients. Nevertheless some possible factors for dissatisfaction are pointed out.


Computational identification of differentially-expressed genes as suggested novel COVID-19 biomarkers: A bioinformatics analysis of expression profiles.
COVID-19 was declared a pandemic in March 2020, and since then, it has not stopped spreading like wildfire in almost every corner of the world, despite the many efforts made to stem its spread. SARS-CoV-2 has one of the biggest genomes among RNA viruses and presents unique characteristics that differentiate it from other coronaviruses, making it even more challenging to find a cure or vaccine that is efficient enough. This work aims, using RNA sequencing (RNA-Seq) data, to evaluate whether the expression of specific human genes in the host can vary in different grades of disease severity and to determine the molecular origins of the differences in response to SARS-CoV-2 infection in different patients. In addition to quantifying gene expression, data coming from RNA-Seq allow for the discovery of new transcripts, the identification of alternative splicing events, the detection of allele-specific expression, and the detection of post-transcriptional alterations. For this reason, we performed differential expression analysis on different expression profiles of COVID-19 patients, using RNA-Seq data coming from NCBI public repository, and we obtained the lists of all differentially expressed genes (DEGs) emerging from 7 experimental conditions. We performed a Gene Set Enrichment Analysis (GSEA) on these genes to find possible correlations between DEGs and known disease phenotypes. We mainly focused on DEGs coming out from the analysis of the contrasts involving severe conditions to infer any possible relation between a worsening of the clinical picture and an over-representation of specific genes. Based on the obtained results, this study indicates a small group of genes that result up-regulated in the severe form of the disease. EXOSC5, MESD, REXO2, and TRMT2A genes are not differentially expressed or not present in the other conditions, being for that reason, good biomarkers candidates for the severe form of COVID-19 disease. The use of specific over-expressed genes, whether up-regulated or down-regulated, which have an individual role in each different condition of COVID-19 as a biomarker, can assist in early diagnosis.


Occupational exposure to asbestos and urinary bladder cancer.
By the use of transmission electron microscopy (TEM) and energy dispersion spectrometry the amount (mean value mean = 191 +/- 94 fibers/mg of tissue) and the type (chrysotile and tremolite) of asbestos fibers have been determined in tissue samples of four bladder cancer patients affected by pulmonary asbestosis, working in the same plant producing asbestos-cement pipes and boards. Similar measurements were carried out on samples of bladder cancers of eight control patients not professionally exposed to asbestos. Only five of them also revealed chrysotile fibers (mean = 151 +/- 196 fibers/mg of tissue). The paucity of the study and control cases and the small quantitative difference between them regarding the presence of infraneoplastic asbestos fibers does not consent us to hypothesize a causal relationship between tumor and occupational exposure.


Abruptio placentae in cynomolgus macaques (Macaca fascicularis): male bias.
Abruptio placentae is a serious problem with a high rate of maternal and fetal mortality and documented sexual dimorphism in reoccurrence. Macaca fascicularis is a well-described reproductive model; however, there are no data available regarding sexual dimorphism in abruptio placentae in these species. A retrospective study of pathology and medical records in a large colony of M. fascicularis was performed. Placental specimens were analyzed. The incidence of placenta abruptio in the colony was 15.7/1000 births. In the abruptio placentae group, male fetuses had lower placental disk length and increased femur length compared with female fetuses. The feto-pacental ratio and fetal weight were lower in the male fetuses in the abruption group compared with those in the stillbirth group without abruption placentae. This is the first documentation of male bias in placental and fetal development in abruptio placentae in non-human primates.


Survival and Prognostic Factors of Colorectal Liver Metastases After Surgical and Nonsurgical Treatment.
Colorectal cancer is one leading cause of cancer-related death worldwide, and distant metastases determine an unfavorable prognosis. Surgical resection of colorectal liver metastases (CRLM) improves survival and provides the chance for cure. The aim of this study was to prospectively analyze the outcome of patients with CRLM in a population-based manner, and thereby, to compare the prognosis of patients undergoing resection with those receiving nonsurgical treatment. Moreover, we set out to identify and confirm important prognostic factors after resection of CRLM. We analyzed the outcome of 506 patients diagnosed with CRLM in our institution from 1996 to 2011. Survival and the impact of clinical and pathologic factors were analyzed by univariate analysis. Important independent prognostic factors were analyzed by multivariate analysis. The 5-year overall survival rate (5y-OSR) for patients receiving resection of CRLM (n = 152) was 46% (95% confidence interval (CI), 37%-54%) compared with a 5y-OSR of 6% (95% CI, 4%-9%) for patients treated nonsurgically (n = 354). There was no perioperative mortality. Multivariate analysis revealed, among other factors, good performance status of the patient (low American Society of Anesthesiologists score), the absence of extrahepatic metastases, < 5 metastatic lesions, and a tumor-free resection margin (R0) as important, independent prognostic factors. Importantly, repeated hepatic resections of CRLM performed in 13 patients were associated with an excellent outcome (5y-OSR, 47%; 95% CI, 17%-72%). Surgical resection, which can be performed with tolerable site-effects, is the first choice for patients diagnosed with metachronous and synchronous CRLM. Of note, repeated resections should be advised in recurrent intrahepatic colorectal cancer whenever possible.


Involvement of intracellular calcium and protein phosphatases in long-term depression of A-fiber-mediated primary afferent neurotransmission.
Long-term depression (LTD) of monosynaptic and polysynaptic excitatory postsynaptic potentials (EPSPs) in substantia gelatinosa (SG) neurons can be induced by brief high-frequency electrical stimulation (HFS, 300 pulses at 100 Hz) of primary afferent fibers in dorsal roots. Here we examined the possible cellular mechanism underlying spinal LTD. Conventional intracellular recordings were made from SG neurons in a transverse slice-dorsal root preparation of the young rat lumbar spinal cord. LTD of both monosynaptic and polysynaptic EPSPs was induced in 16 of 24 SG neurons by HFS of dorsal root in either the presence or absence of the GABA(A) receptor antagonist bicuculline and the glycine receptor antagonist strychnine. Loading the postsynaptic cell with BAPTA, an intracellular Ca(2+) chelator, almost completely blocked the induction of LTD. Induction of LTD was abolished by bath application of calyculin A (100 nM), a potent inhibitor of protein phosphatases 1 and 2A. These results indicate that: (i) a rise in postsynaptic Ca(2+) is necessary for LTD induction, (ii) synaptic activation of protein phosphatases 1 and 2A plays an important role in the induction of LTD of primary afferent A-fiber neurotransmission in the young rat spinal cord, and (iii) the effect of LTD may be physiologically relevant for transmission and integration of sensory information, including nociception.