Fine needle aspiration of an intranodal follicular dendritic cell sarcoma: A case report with molecular analysis and review of the literature.
Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm of follicular dendritic cell origin which can present a diagnostic challenge. Due to the rarity of this neoplasm, its molecular pathogenesis has not been fully elaborated. A previous series of 13 cases reported that 38% contained mutations of genes encoding proteins involved in negative regulation of NF-κB. NF-κB is a family of transcription factors regulated through multiple cellular processes known as the canonical and noncanonical pathways. Here we present the case of a 62-year-old man who presented with abdominal pain and systemic symptoms and was found to have a mass in the porta hepatis. Fine needle aspiration cytology demonstrated a spindle cell neoplasm with vesicular chromatin and prominent nucleoli with admixed lymphocytes. Surgical resection showed an intranodal, 7.3 × 5.5 × 3.5 cm, solid mass composed of plump, spindle to histiocytoid cells with ovoid nuclei and small, prominent nucleoli arranged in a whorled and fascicular pattern. The lesional cells stained positively for CD21, CD23, and CD35 by immunohistochemistry, consistent with a diagnosis of FDCS. Next-generation sequencing revealed pathologic mutations in three genes involved in NF-κB regulation pathways: NFKBIA, TNFAIP3, and TRAF3. A pathologic TP53 mutation was also identified. This case report supports prior associations of the NF-κB pathway dysregulation and FDCS. Additionally, it is the first reported FDCS case with TRAF3 mutation as well as the first reported case to suggest disruption in both the canonical and noncanonical NF-κB pathways in the same lesion.


Old patients with hypertension. A 25-year observational study of a geographically defined population (Dalby), aged 67 years at entry.
To evaluate the impact of hypertension and other risk factors on mortality, in particular cardiovascular mortality, in a geographically defined population of elderly subjects. An observational 25-year study of a total population. The local health centre in the village of Dalby in southern Sweden. All men and women born in 1902 or 1903, living in Dalby, were, at the age of 67, invited for medical and psychological examinations. The population comprised 188 subjects (109 men and 79 women); 156 (83%) of them took part in the first medical examination. Blood pressure, heart rate, weight and height were measured and laboratory tests performed at entry. Blood pressures were thereafter recorded six times, and this report is based on a 25-year follow-up period ending in October 1994. Survival analyses were performed, based on definition of underlying causes of death, divided into all-cause and cardiovascular. At entry, females had higher blood pressure than males, both at baseline and during the first 16 years of the study, regardless of whether they were hypertensives or not. Most men smoked but only a few women. At the end of the follow-up of the present study in 1994, 138 out of 156 (88%) subjects had died and only 18 (12%) remained alive; 78 (57%) had died of a cardiovascular disease. In men, a diagnosis of hypertension as well as increased blood pressure at entry was associated with increased mortality. In women this was the case for blood pressure and risk of cardiovascular mortality. In men, both systolic and diastolic blood pressures during the study were significant risk factors for death, whereas in women this was not the case. Elderly male hypertensives ran an increased mortality risk even though they were treated according to the then current guidelines; female hypertensives seemed to run the same risk of dying as normotensive females.


A critical evaluation of the use of mutagenesis, carcinogenesis, and tumor promotion data in a cancer risk assessment of 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Regulatory agencies in the Western Hemisphere are currently assessing the potential human health risks of environmental contamination by 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). Some U.S. agencies such as the Environmental Protection Agency (EPA) and Centers for Disease Control (CDC) have assumed that TCDD behaves as a tumor initiator in animals and have used linear low-dose mathematical extrapolation models for estimating any human risk. In contrast, the Ontario Ministry of the Environment, the State Institute of National Health of The Netherlands, and the Federal Environmental Agency of the Federal Republic of Germany have concluded that TCDD does not have initiator activity; these agencies have advocated a risk extrapolation approach which applies a safety factor to a no-observable-effect level. Estimations of the potential risk obtained by these two approaches can differ by three to four orders of magnitude and have a major impact on the allocation of resources within the affected countries. This paper critically reviews the TCDD bacterial, animal, and human data on mutagenesis, carcinogenesis, and tumor promotion and concludes that the scientific evidence does not support risk estimations which are based on TCDD as a tumor initiator. Rather, the animal data overwhelmingly support TCDD as a tumor promoter. Risk estimations which incorporate tumor promotion activity more accurately reflect the scientific understanding of TCDD's mechanism of action and provide better estimates of its risk.


Opening our eyes to Global Health; a philosophy of universal values.
Globalization is advancing at a pace. As we strive to introduce 'Global Health' into clinical curricula we risk fundamental misunderstandings unless we clearly define what we aim to achieve. Clinicians must be prepared for a life time of uncertainty, change and challenge. The fluctuating world arena will undoubtedly impact on their future work in ways we cannot predict. Population migration, climate change and shifts in cultural dominance are already at play. Global health risks being translated through the eyes of Western ideology as disease-based curricula focused paternalistically on 'helping' the developing world. We must not lack humility to open eyes to learning within the context of increasingly diverse environments and patient populations. Global health is as 'local' as it is 'international'. It should be viewed, I argue, as a philosophy based on the values and expectations found within ourselves and our communities. Responding to globalization lies not only in knowledge but embraces human rights, justice and, most importantly, self-awareness. Knowledge is more easily translated into curriculum objectives. We risk letting future clinicians and their patients down if we ignore the other universal values.


Prosthetic Joint Infections and Cost Analysis?
Prosthetic joint infection is a devastating complication of arthroplasty surgery that can lead to debilitating morbidity for the patient and significant expense for the healthcare system. With the continual rise of arthroplasty cases worldwide every year, the revision load for infection is becoming a greater financial burden on healthcare budgets. Prevention of infection has to be the key to reducing this burden. For treatment, it is critical for us to collect quality data that can guide future management strategies to minimise healthcare costs and morbidity / mortality for patients. There has been a management shift in many countries to a less expensive 1-stage strategy and in selective cases to the use of debridement, antibiotics and implant retention. These appear very attractive options on many levels, not least cost. However, with a consensus on the definition of joint infection only clarified in 2011, there is still the need for high quality cost analysis data to be collected on how the use of these different methods could impact the healthcare expenditure of countries around the world. With a projected spend on revision for infection at US$1.62 billion in the US alone, this data is vital and urgently needed.


The functional exercise capacity is correlated with global functioning in patients with schizophrenia.
The 6-minute walk test (6MWT) is commonly used to measure the functional exercise capacity in chronic patients with cardiovascular diseases. The purpose of this study was to determine whether the 6MWT is associated with the global assessment of functioning (GAF) score in patients with schizophrenia. A total of 68 male and 25 female in-patients with schizophrenia (34.6 ± 9.7 years; body mass index = 24.9 ± 4.4) performed a 6MWT and were assessed with the GAF scale and the Psychosis Evaluation tool for Common use by Caregivers (PECC). The mean distance walked on the 6MWT was 587.3 ± 98.4 m, while the mean GAF score was 52.0 ± 10.4. The Pearson's correlation coefficient between the 6MWT and the GAF score was 0.59 (P < 0.001), indicating a moderate association between both measures. The 6MWT was also significantly related to negative (r = -0.45, P < 0.001), depressive (r = -0.48, P < 0.001) and cognitive (r=, P) symptoms and with body mass index (r = -0.31, P < 0.005), smoking behaviour (r = -0.36, P < 0.001)) and dose of antipsychotic medication (r = -0.38, P < 0.001). Next to the GAF scale, clinicians in in-patient settings should consider incorporating the 6MWT into their test battery to measure the functional consequences of schizophrenia and its treatment.


Signet Ring Cell Histology Confers Worse Overall Survival in Treated Esophageal Adenocarcinoma.
Signet ring cell (SRC) histology is regarded as a poor prognostic indicator for esophageal cancer. The objectives of this study were to understand the clinical presentation and stage-specific survival outcomes of patients with SRC and nonsignet adenocarcinoma (AC). From 2004 to 2016, 140,324 patients were diagnosed with esophageal and gastroesophageal junction cancers in the National Cancer Database. Demographics, tumor variables, and treatment were studied. Overall survival was shown by the Kaplan-Meier method, and random survival forest identified important predictors. SRC patients (N = 3825) comprised roughly 3% of esophageal cancers per year. SRC patients were less likely to present at early stage disease (cStage I: 10.2% vs 17.8% for AC; P < .001) and more likely to have pathologic upstaging (28% vs 16%, P < .001) and less pathologic downstaging after neoadjuvant therapy (36% vs 48%, P < .001). More SRC patients had positive margins after resection (15% vs 6.0%, P < .001). In a stage-matched comparison median survival for SRC patients was worse than for AC patients (cStage I: 60 vs 113 months; cStage II: 31 vs 40 months; cStage III: 22 vs 30 months). Clinical tumor and nodal stage, chemotherapy sequence, and age were important predictors of survival. SRC patients had worse survival than their AC counterparts. Worse biology and higher rates of incomplete resection in SRC should steer patients away from undergoing limited resection, such as endoscopic submucosal dissection, even when identified at very early stages. In future esophageal cancer staging iterations, separating SRC from AC appears to be indicated because of their different clinical behavior and response to therapy.


Adenine Modification at C7 as a Viable Strategy to Potentiate the Antimalarial Activity of Quinolones.
Although many quinolones have shown promise as potent antimalarials, their clinical development has been slow due to poor performance in vivo. Insights into structural modifications that can improve their therapeutic potential will be very valuable in this vibrant area of research. Our studies involving a library of quinolones which vary in substitution pattern at N1, C3, C6 and C7 positions have shown that the presence of adenine moiety at C7 can bring a noticeable improvement in activity compared to other heterocyclic groups at this location. The most potent compound emerged from this study showed IC50 values of 0.38 μM and 0.75 μM against chloroquine-sensitive and -resistant (W2) strains, respectively. Docking analysis in the Qo site of cytochrome bc1 complex revealed the contribution of a key H-bonding interaction from the adenine unit in target binding. This corroborates with compound-induced loss of mitochondrial functions. These findings not only open avenues for further exploration of antimalarial potential of adenine-modified quinolones, but also suggests broader opportunities during lead-optimization against other antimalarial targets.


Peroral Endoscopic Myotomy for Type III Achalasia of Chicago Classification: Outcomes with a Minimum Follow-Up of 24 Months.
There are only few studies about the outcomes of peroral endoscopic myotomy (POEM) for type III achalasia in a relatively large population to date. The purpose of this study was to explore the long-term efficacy of POEM for patients with type III achalasia. There were a total of 32 consecutive patients with type III achalasia undergoing POEM in our hospital from July 2012 to October 2014. Clinical date of general characteristics, procedure-related parameters and adverse events, symptom relief, and the high-resolution manometry outcomes before and during the periodic follow-up were retrospectively collected and analyzed. All of the 32 patients underwent POEM successfully with a median operation time of 34.9 min (range 17.9-88.6 min). No serious complications related to POEM were encountered. Treatment success was achieved in 90.6% cases during a median follow-up period of 27.0 months (range 24-51 months). The mean pretreatment and post-treatment Eckardt scores were 7.2 and 1.4, respectively (P < 0.001), and mean LES pressure also decreased from a mean of 39.2 to 19.0 mmHg after the procedure (P < 0.001). Both of the gas-related complication and clinical reflux complication rates were 18.8%. Our results confirm that POEM for type III achalasia of Chicago Classification is effective with a long-term symptom relief in 90.6% cases. But a further, prospective study is needed to evaluate whether POEM outcome could be correlated with manometric subtypes according to Chicago Classification.


The anaerobic degradation of L-serine and L-threonine in enterobacteria: networks of pathways and regulatory signals.
The mechanisms controlling the biosynthesis and degradation of l-serine and l-threonine are remarkably complex. Their metabolism forms a network of pathways linking several amino acids, central primary metabolites such as pyruvate, oxaloacetate and 3-phosphoglycerate, and C1 metabolism. Studies on the degradation of these amino acids in Escherichia coli have revealed the involvement of fascinating enzymes that utilise quite diverse catalytic mechanisms. Moreover, it is emerging that both environmental and metabolic signals have a major impact in controlling enzyme synthesis This is exemplified by the anaerobically regulated tdc operon, which encodes a metabolic pathway for the degradation of serine and threonine. Studies on this pathway are beginning to provide insights into how an organism adapts its genetic makeup to meet the physiological demands of the cell.


Erdosteine prevents doxorubicin-induced cardiotoxicity in rats.
The clinical use of doxorubicin (Dxr) is limited by its cardiotoxic effects which are mediated by oxygen radicals. The purpose of this study was to investigate in vivo protective effects of erdosteine, an antioxidant agent because of its secondary active metabolites in vivo, against the cardiotoxicity induced by Dxr in rats. Three groups of male Sprague-Dawley rats (60 days old) were used. Group 1 was untreated group used as control; the other groups were treated with Dxr (single i.p. dosage of 20 mg kg(-1) b.wt.) or Dxr plus erdosteine (10 mg kg(-1) day(-1), orally), respectively. Erdosteine or oral saline treatment was done starting 2 days before Dxr for 12 days. The analyses were done at the 10th day of Dxr treatment. The protein carbonyl content, the activities of myeloperoxidase, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase (CK) as well as heart rate and blood pressures were significantly increased in Dxr group in comparison with the other groups. However, pulse pressure was decreased in Dxr group. The body and heart weights were decreased in both Dxr administered groups in comparison with control group. Disorganization of myocardial histology, picnotic nuclei, edema, and increase in collagen content around vessels were seen in the slides of Dxr group, whereas normal myocardial microscopy was preserved in Dxr plus erdosteine group. Collectively, these in vivo hemodynamic, enzymatic and morphologic studies provide an evidence for a possible prevention of cardiac toxicity in Dxr-treated patients.


PAH related effects on fish in sedimentation ponds for road runoff and potential transfer of PAHs from sediment to biota.
Road runoff is an important source of pollution to the aquatic environment, and sedimentation ponds have been installed to mitigate effects on the aquatic environment. The purpose of this study was to investigate if a) fish from sedimentation ponds were affected by road pollution and; b) the transfer of PAHs from road runoff material to aquatic organisms was substantial. Minnow from a sedimentation pond (Skullerud) near Oslo (Norway) had higher levels of CYP1A enzyme and DNA stand breaks than minnow from the nearby river, but high concentrations of PAH-metabolites in bile revealed that both populations were highly exposed. Principal component analysis revealed that CYP1A and age of fish were correlated, while levels of PAH-metabolites were not correlated to CYP1A or DNA damage. Minnow from a lake un-affected by traffic had much lower levels of PAH-metabolites than the exposed fish, and also an improved condition. The latter results indicate that fish health was affected by road runoff. A closer investigation of PAH levels of the ecosystems of two sedimentation ponds (Skullerud and Vassum) and nearby environments were conducted. The concentration of the 16 EPA PAHs in sediments of the sedimentation ponds were high (1900-4200ngg(-1)), and even higher levels were observed in plants. Principal component analysis of selected ion chromatograms of PAHs showed a clear separation of plants vs. sediments. The plants preferentially accumulated the high molecular PAHs, both from sedimentation ponds with a petrogenic PAH isomer ratio in sediments; and from a lake with pyrogenic PAH isomer ratio in sediments.


[Fluid overload and arterial hypertension in hemodialysis patients].
The water sodium overload is a factor of morbi-mortality and its treatment is one of the markers of adequacy of the hemodialysis treatment. Its first clinical assessment was improved by tools such as echocardiography and ultrasonography of the inferior vena cava, the per-dialytic curve of plasma volume, measuring BNP or proBNP and by impedancemetry. The combination of the evaluation of these parameters and of the clinical situation allows one to assess the extracellular overload, the state of the blood volume and the potential of plasma refilling. The latter is a key factor of the per-dialytic hemodynamic tolerance. It is itself a determining factor in weight can be achieved at the end of the session. Getting the "dry" weight can require modifications of the prescriptions of the hemodialysis sessions, a filling by albumin even a drugs support. Finally, the overload treatment is the central part of the treatment of arterial hypertension, which has to benefit however often from antihypertensive treatment the profit of which is demonstrated.


Simulated weightlessness and bone metabolism: decrease of alkaline phosphatase activity in the femoral diaphysis of rats.
The effect of simulated weightlessness on bone metabolism was investigated in the skeletal unloading for up to 9 days. The skeletal unloading was designed by using the model of hindlimb hang in rats. The food ingestion of rats with the skeletal unloading was not altered in comparison to that of normal rats. Calcium concentration in the serum was not significantly altered by the skeletal unloading for 9 days, while the serum inorganic phosphorus concentration was significantly decreased at 6 and 9 days. Calcium content in the femoral diaphysis was not altered by the skeletal unloading for 9 days. However, the activities of alkaline and acid phosphatases in the femoral diaphysis were markedly decreased by the skeletal unloading. The decrease in bone alkaline phosphatase activity was seen at 2 days with the skeletal unloading. The present results demonstrate that the skeletal unloading with hindlimb hang can induce the disorder of bone metabolism. This model is useful for studying the effects of simulated weightlessness on bone metabolism.


Gut microbiota in nonalcoholic fatty liver disease: a PREDIMED-Plus trial sub analysis.
To evaluate the changes in the gut microbiota associated with changes in the biochemical markers of nonalcoholic fatty liver disease (NAFLD) after a lifestyle intervention with the Mediterranean diet. Participants (n = 297) from two centers of PREDIMED-Plus trial (Prevención con Dieta Mediterránea) were divided into three different groups based on the change tertile in the Hepatic Steatosis Index (HSI) or the Fibrosis-4 score (FIB-4) between baseline and one year of intervention. One-year changes in HSI were: tertile 1 (T1) (-24.9 to -7.51), T2 (-7.5 to -1.86), T3 (-1.85 to 13.64). The most significant differences in gut microbiota within the year of intervention were observed in the T1 and T3. According to the FIB-4, participants were categorized in non-suspected fibrosis (NSF) and with indeterminate or suspected fibrosis (SF). NSF participants showed higher abundances of Alcaligenaceae, Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Peptostreptococcaceae, Verrucomicrobiaceae compared to those with SF. Then, participants were divided depending on the FIB-4 tertile of change: T1 (-89.60 to -5.57), T2 (-5.56 to 11.4), and T3 (11.41 to 206.24). FIB-4 T1 showed a decrease in Akkermansia and an increase in Desulfovibrio. T2 had an increase in Victivallaceae, Clostridiaceae, and Desulfovibrio. T3 showed a decrease in Enterobacteriaceae, and an increase in Sutterella, Faecalibacterium, and Blautia. A relation between biochemical index changes of NAFLD/NASH (HSI and FIB-4) and gut microbiota changes were found. These observations highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations.


High-flow catheter ventilation during major tracheobronchial reconstruction.
Anesthetic management during tracheobronchial reconstruction is a concern to the anesthetist, who must maintain satisfactory gas exchange while ensuring adequate exposure to the trachea. The technique for high-flow catheter ventilation was first described for bronchoscopy, and it involves positive-pressure breathing with a high flow (40 to 60 L/min) of oxygen. This flow is directed to a semirigid catheter inserted in the endotracheal tube and around which the tracheobronchial anastomosis can be done without interruption. The value of the technique was tested in 18 patients undergoing tracheobronchial reconstructions. Patients' ages ranged from 22 to 69 years and the average duration of catheter ventilation was 35 minutes. Regardless of the duration of high-flow catheter ventilation good arterial blood gas values were maintained in all patients. In six patients, the average oxygen tension (measured at 5 minute intervals) was 416 mm Hg and the average carbon dioxide tension was 34 mm Hg. One patient developed surgical emphysema during the procedure. The high-flow catheter ventilation provides specific advantages during tracheobronchial procedures: avoidance of endotracheal manipulations, unobstructed field during surgical reconstruction, and good oxygenation throughout the procedure.


Evaluation of the clinical application of cystatin C, a new marker of the glomerular filtration rate, for the initial dose-setting of arbekacin.
Recent studies have shown that serum cystatin C is a better marker for measuring the glomerular filtration rate (GFR) than the conventional method, using serum creatinine concentration. The purpose of this study is to evaluate the clinical application of serum cystatin C as a marker of GFR to determine the initial dosage of arbekacin, an antibiotic primarily excreted via the kidneys. In this study, the predictability of serum arbekacin peak and trough concentrations were assessed using estimated population mean GFR values calculated from either serum creatinine (Cockcroft-Gault equation) or cystatin C (Sjöström equation) concentrations. Ninety-five patients treated with arbekacin for methicillin-resistant Staphylococcus aureus infection were divided into three groups according to their GFR values estimated by the serum cystatin C concentration as follows: normal to mild (GFR > 70 mL/min, n = 40), moderate (30 </= GFR </= 70 mL/min, n = 41) and severe (GFR < 30 mL/min, n = 14) renal impairment. The mean GFR (+/-SD) of 95 patients predicted by serum cystatin C concentration (64.6 +/- 30.6 mL/min) was significantly lower (P < 0.001) than predicted by serum creatinine concentration (77.4 +/- 43.9 mL/min). Prediction (difference of mean prediction error, DeltaME) of the serum arbekacin concentration using the estimated GFR based on the serum cystatin C concentration was significantly less biased at the peak and trough concentrations than those determined using serum creatinine concentration. The accuracy of prediction (difference of the mean absolute error, DeltaMAE) using serum cystatin C concentration was significantly better than with serum creatinine for both serum peak and trough concentrations in patients with moderately decreased GFR. However, there were no significant differences in the DeltaMAE of normal to mild and severe renally impaired patients. These results suggest that serum cystatin C is a useful marker of GFR for determining the initial dosage of arbekacin, especially in patients with moderate impairment of renal function.


Complex regional pain syndrome: a review.
Complex regional pain syndrome (CRPS), formerly known as "reflex sympathetic dystrophy," is a chronic neurological disorder characterized by disabling pain, swelling, vasomotor instability, sudomotor abnormality, and impairment of motor function. The disorder usually develops after minor trauma or surgery. No specific diagnostic test is available and, hence, diagnosis is based mainly on history, clinical examination, and supportive laboratory findings. This review gives a synopsis of CRPS and discusses the principles of management based on the limited available literature in the area. A literature search was conducted using electronic bibliographic databases (Medline, Embase, Pubmed, CENTRAL) from 1970 to 2006. Keywords complex regional pain syndrome, reflex sympathetic dystrophy, neuropathic pain, and causalgia were used for the search. Relevant articles from the reference lists in retrieved articles were also studied. There were 3,771 articles published in the area. Seventy-six randomized controlled trials were identified. Most studies were on the role of sympathetic blockade in the treatment of CRPS (n = 13). The role of sympathectomy is unclear, with some studies showing transient benefit and others showing no beneficial effects, with most studies containing only a small number of patients. Nine studies were on bisphosphonates or calcitonin. Studies involving bisphosphonates showed benefit, but studies involving calcitonin showed no definite benefit. Four studies were on cognitive behavioral therapy, physiotherapy, or occupational therapy, all of which demonstrated a potential beneficial effect. Three studies on spinal cord stimulation and two studies each on acupuncture, vitamin C, and steroid all showed a potential beneficial effect in pain reduction. The remaining studies were on miscellanous therapy or combination therapy, making it difficult to draw any conclusions on the effect of treatment. There is very little good evidence in the literature to guide treatment of CRPS. Early recognition and a multidisciplinary approach to management seems important in obtaining a good outcome. Treatments aimed at pain reduction and rehabilitation of limb function form the mainstay of therapy. Comorbidities, such as depression and anxiety, should be treated concurrently.


Distribution of arsenic and oxidative stress in mice after rice ingestion.
This study evaluated the effects of rice naturally contaminated with arsenic (As) and the same As-species added as solubilized-salt on the redox state and the As distribution in male mice. The total As amount in the Brazilian polished rice used in this study was 169.81±6.12ngg-1. Indeed, the concentrations of As species were 40.77ngg-1 (arsenite, As3+), 65.71ngg-1 (dimethylarsinic acid, DMA), 11.90ngg-1 (monomethylarsonic acid, MMA), and 25.96ngg-1 (arsenate, As5+). In this sense, animals were randomly divided into seven groups with six mice per group: I) control: habitual food; II) rice I: diet containing 10% of rice naturally containing As (4.08μg As3+/kg diet, 6.57μg DMA/kg diet, 1.19μg MMA/kg diet, and 2.60μg As5+/kg diet); III) rice II: diet containing 20% of rice naturally containing As (8.15μg As3+/kg diet, 13.14μg DMA/kg diet, 2.38μg MMA/kg diet, and 5.19μg As5+/kg diet); IV) rice III: diet containing 40% of rice naturally containing As (16.31μg As3+/kg diet, 26.28μg DMA/kg diet, 4.76μg MMA/kg diet, and 10.38μg As5+/kg diet); V) spiked feed I: diet containing As species as solubilized-salt (concentration equivalent to group II); VI) spiked feed II: diet containing As species as solubilized-salt (concentration equivalent to group III); VII) spiked feed III: diet containing As species as solubilized-salt (concentration equivalent to group IV). The time of treatment was 100days. After euthanasia, it was observed an increase in total As concentration in tissue samples of groups treated with diet containing rice naturally contaminated and diet containing As species. For instance, the highest As concentrations (higher than 330ngg-1) was observed in the bladder of animals belonging to Rice II and III and spiked feed III groups. Furthermore, it was verified the highest As concentrations in bladder > hair > lung > kidney > liver > blood. We also observed the presence of DMA and As5+ in liver and kidneys. Regarding oxidative stress biomarkers, we observed significant reduction of Glutathione (GSH) concentration in blood of animals belonging to groups IV, V, VI and VII. Besides, the antioxidant enzymes activities, Glutathione Peroxidase (GSH-Px), Catalase (CAT) and superoxide dismutase (SOD), increased significantly in blood of animals belonging to group VII. On the other hand, it was not observed differences in nitric oxide (NO) levels among all the groups used in this study and the control group. Thus, we conclude that some minor effects were found in mice exposed to the diet containing the highest amount of rice naturally contaminated with As species. These findings contribute to evaluate the safety of human dietary consumption.


How Enclosure and Spatial Organization Affect Residents' Use and Experience of a Dementia Special Care Unit: A Case Study.
We aim to gain insight into how a dementia special care unit is used and experienced by its residents and what design aspects are important therein. In Flanders, housing for people with dementia evolves toward small-scale, homelike environments. As population aging challenges the affordability of this evolution, architects and other designers are asked to design dementia special care units that offer the advantages of small scaleness within the context of large-scale residential care facilities. How these units are used and experienced is not systematically evaluated. A case study was conducted in a recently built residential care facility where a dementia special care unit was foreseen on the ground floor, yet after a few months was moved to the top floor. The case study combined architectural analysis, participant observation, and qualitative interviews with residents and care staff. Comparing the original situation on the ground floor with the new situation on the top floor highlights how enclosure (physical and visual access to outside and the rest of the facility) and spatial organization affect how residents use and experience a dementia special care unit. Depending on the type and stage of dementia, residents may have different needs for space to move, sensory stimuli, and social contact. In order to meet these different needs, confining residents to a dementia special care unit to the top floor should be avoided unless it is carefully designed, providing sufficient freedom of movement and connection with the outside world.


Neural changes in the ventral and dorsal visual streams during pattern recognition learning.
The learning process related to pattern and object recognition is difficult to study because the human brain has a remarkable capacity to recognise complex visual forms from early infancy. In the present study, we investigated on-going neural changes underlying the learning process of visual pattern recognition by means of a device substituting audition for vision. Functional MRI evidenced the gradual pattern recognition-induced recruitment of the ventral visual stream, bilaterally, from learning session 1 to session 3, and a slight decrease in these activation foci from session 3 to session 4. The initial increase in activation is thought to reflect the gradually enhanced visualisation of patterns in the subjects' mind across sessions. By contrast the subsequent decrease reported at the end of the training period is interpreted as the progressive optimisation of neuronal responses elicited by the task. Our results, in accordance with previous observations, suggest that the succession of activation increase and decrease in sensori-motor areas could be a general rule in sensory and sensori-motor learning.


Radioautographic study of 3H-GABA uptake in the oculomotor nucleus of the cat.
The uptake of tritiated gamma-aminobutyric acid (3H-GABA) in the oculomotor nucleus of the cat was studied, using light and electron microscopic examination of radioautograms after intracerebral in vivo administration of the amino-acid. A glial uptake by oligodendrocytes was seen together with a neuronal uptake of the tracer in a certain type of axon terminals found in synaptic contact with both dendrites and soma, some of them exhibiting all the ultrastructural features of motoneurons. Previous neurochemical, electrophysiological and immunocytochemical studies indicate that GABA might well be the inhibitory neurotransmitter in the vestibuloocular reflex arc. The present results show that a morphological substrate exists for the presumed postsynaptic GABAergic inhibition of ocular motoneurons, at least in the oculomotor nucleus of the cat.


HPTLC fingerprinting and quantification of lignans as markers in sesame oil and its polyherbal formulations.
Sesamum (Sesamum indicum) seed and its oil have been in use in Indian traditional medicine, 'Ayurveda' since antiquity. However, there has been no attempt to standardize the polyherbal formulations containing sesamum oil as the main ingredient in terms of its active principle or marker compound. Biologically active lignans in sesamum oil are identified as the marker compound for the oil and its formulations. In this report, a simple, rapid and sensitive HPTLC method is described for the first time to identify and quantify sesamin and sesamolin, the major lignans of the sesamum oil and the method was applied to polyherbal formulations containing the oil for their quantitative estimation. The method was validated in terms of its calibration curve, limits of detection and quantification, precision, accuracy and robustness following standard protocols. The method thus developed was applied to sesamum oil and its commercial herbal formulations to quantify sesamin and sesamolin. The method for fingerprints of the formulations in the form of densitogram following charring of the chromatographic plate was also developed that could be useful for marker-based quality assurance of the polyherbal products containing sesamum oil.


Morroniside regulates hair growth and cycle transition via activation of the Wnt/β-catenin signaling pathway.
Hair loss is characterized by a shortened hair anagen phase and hair follicles (HF) miniaturization. Morroniside is the most abundant iridoid glycoside extracted from Cornus officinalis and has various bioactivities in different cell functions and tissue regeneration. In this study, we investigated the effects and the underlying mechanism of morroniside on hair growth and regulation of HF cycle transition. Morroniside treatment significantly enhanced outer root sheath cell (ORSC) proliferation and migration in vitro. Additionally, morroniside upregulated Wnt10b, β-catenin and lef1. The enhanced ORSC proliferation and migration due to morroniside treatment were partly rescued by a Wnt/β-catenin signaling inhibitor, DKK1. Furthermore, in a hair-induced mouse model, morroniside injection accelerated the onset of anagen and delayed HF catagen, as shown by histological examination. Immunohistochemical analyses revealed that Wnt/β-catenin signaling pathway expression was upregulated in the HFs. These findings suggest that morroniside regulates HF growth and development partly through the Wnt/β-catenin signaling pathway and may be a potential treatment for hair loss.


Informal Caregiving Provision for Disabled or Elderly in the Families and Work Productivity: Evidence from 11 Waves of an Australian Population-Based Cohort.
Informal carers are family members, friends or neighbours who care for persons in need. In 2018, around one in ten Australians offered some informal care, most of which was unpaid. It is essential to comprehend how informal caregivers' productivity at work is affected by their caregiving responsibilities. We examine the association between informal caregiving and productivity loss in Australia. We utilised 11 waves of data drawn from the Household, Income and Labour Dynamics in Australia (HILDA) survey. Longitudinal random-effects logistic regression and random-effects Poisson regression techniques were used to assess the between-person differences in the association between informal caregiving and productivity loss (absenteeism, presenteeism and working hour tension). The results suggest informal caregiving is associated with a higher rate of absenteeism, presenteeism and working hour tension. We reveal that absence/leave rates at work are greater for those with lighter, moderate and intensive care responsibilities than those without caregiving responsibilities, given other covariates reference categories remain constant. Our findings also indicate that workers with intensive, moderate, and light caregiving responsibilities have considerably higher rates of working hour tension than their peers without caregiving commitments if other covariate reference categories are held constant. The result further shows that, on average, an individual with lighter, moderate and intensive caregiving roles had incurred AUD 276.13, AUD 246.81, and AUD 1927.16, respectively, in absenteeism costs annually compared with their counterparts without caregiving duties. Our study reveals that working-age caregivers experience greater absenteeism, presenteeism and working hour tension. Adverse effects of informal caregiving are required to perform the cost effectiveness of an intervention given to caregivers to improve carer and patient health. Our findings will assist health technology assessment (HTA) practitioners in performing an economic evaluation of interventions given to caregivers by providing the indirect cost (productivity loss) of caregiving.


Preoperative evaluation of the biliary tract.
When clinically suspected, obstructive jaundice presents the clinician with the problem of selecting the most suitable tests and determining the order in which they should be performed. Technology has provided a number of highly specific and quite expensive procedures. The studies most appropriately performed are ultrasonography, percutaneous transhepatic cholangiography, ERCP, flexible choledochoscopy, CT scan of the abdomen, HIDA scan, and intravenous cholangiography. The algorithmic approach is clinically helpful in this situation and is recommended as a useful guide.


Evaluation of Semen Self-Sampling Yield Predictors and CTC Isolation by Multi-Color Flow Cytometry for Liquid Biopsy of Localized Prostate Cancer.
Liquid biopsy (LB) for prostate cancer (PCa) detection could represent an alternative to biopsy. Seminal fluid (SF) is a source of PCa-specific biomarkers, as 40% of ejaculate derives from the prostate. We tested the feasibility of an SF-based LB by evaluating the yield of semen self-sampling in a cohort of >750 patients with clinically localized PCa. The overall SF collection yield was 18.2% (39% when considering only compliant patients), with about a half of the patients (53.15%) not consenting to SF donation. Independent favorable predictors for SF collection were younger age and lower prostate volume. We implemented a protocol to enrich prostate-derived cells by multi-color flow cytometry and applied it on SF and urine samples from 100 patients. The number of prostate-enriched cells (SYTO-16+ PSMA+ CD45-) was variable, with higher numbers of cells isolated from SF than urine (p value < 0.001). Putative cancer cells (EpCAMhigh) were 2% of isolated cells in both specimens. The fraction of EpCAMhigh cells over prostate-enriched cells (PSMA+) significantly correlated with patient age in both semen and urine, but not with other clinical parameters, such as Gleason Score, ISUP, or TNM stage. Hence, enumeration of prostate-derived cells is not sufficient to guide PCa diagnosis; additional molecular analyses to detect patient-specific cancer lesions will be needed.


Evolution of matrinic ethanol derivatives as anti-HCV agents from matrine skeleton.
Twenty-two novel 12N-substituted matrinic ethanol derivatives were synthesized and evaluated for their antiviral activities against HCV taking compound 1 as the lead. The SAR study indicated that the shortening of the 11-butyl chain to ethyl chain did not affect the activity significantly. Out of the target compounds, matrinic ethanol 6a demonstrated a potential anti-HCV effect with an EC50 value of 3.2μM and a SI value of 96.6. The free hydroxyl arm in 6a made it possible as a parent structure to prepare pro-drug for the potential application in HCV treatment. This study provided powerful information on further strategic optimization and development of this kind of compounds into a novel family of anti-HCV agents.


From multidimensional neuropsychological outcomes to a cognitive complication rate: the International Subarachnoid Aneurysm Trial.
The neuropsychological arm of the International Subarachnoid Aneurysm Trial (N-ISAT) evaluated the cognitive outcome of 573 patients at 12 months following subarachnoid haemorrhage (SAH). The assessment included 29 psychometric measures, yielding a substantial and complex body of data. We have explored alternative and optimal methodologies for analysing and summarising these data to enable the estimation of a cognitive complication rate (CCR). Any differences in cognitive outcome between the two arms of the trial are not however reported here. All individual test scores were transformed into z-scores and a 5th percentile cut-off for impairment was established. A principal components analysis (PCA) was applied to these data to mathematically transform correlated test scores into a smaller number of uncorrelated principal components, or cognitive 'domains'. These domains formed the basis for grouping and weighting individual patients' impaired scores on individual measures. In order to increase the sample size, a series of methods for handling missing data were applied. We estimated a 34.1% CCR in all those patients seen face-to-face, rising to 37.4% CCR with the inclusion of patients who were unable to attend assessment for reason related to the index SAH. This group demonstrated significantly more self and carer/relative rated disability on a Health Related Quality of Life questionnaire, than patients classified as having no functionally significant cognitive deficits. Evaluating neuropsychological outcome in a large RCT involves unique methodological and organizational challenges. We have demonstrated how these problems may be addressed by re-classifying interval data from 29 measures into a dichotomous CCR. We have presented a 'sliding scale' of undifferentiated individual cognitive impairments, and then on the basis of PCA-derived cognitive 'domains', included consideration of the distribution of impairments in these terms. In order to maximize sample size we have suggested ways for patients who did not complete the entire protocol to be included in the overall CCR. ISAT TRIAL REGISTRATION: ISRCTN49866681.


Technical considerations for the implementation of the multi-attribute-method by mass spectrometry in a quality control laboratory.
Multi-attribute methods employing mass spectrometry are applied throughout the biopharmaceutical industry for product and process characterization purposes but are not yet widely accepted as a method for batch release and stability testing under good manufacturing practice (GMP) due to limited experience and level of comfort with the technical, compliance and regulatory aspects of its implementation at quality control (QC) laboratories. Here, current literature related to the development and application of the multi-attribute method by peptide mapping liquid chromatography mass spectrometry (MAM) is compiled with the aim of providing guidance for the implementation of MAM in a QC laboratory. This article, focusing on technical considerations, is the first part of a two-tiered publication, whereby the second part will focus on GMP compliance and regulatory aspects. This publication has been prepared by a group of industry experts representing 14 globally acting major biotechnology companies under the umbrella of the European Federation of Pharmaceutical Industries and Associations (EFPIA) Manufacturing & Quality Expert Group (MQEG).


[Gorlin syndrome (nevoid basal cell carcinoma syndrome)].
A 77 year-old male patient with Parkinson's disease and senile dementia had many facial basal cell carcinomas and an ectropion of the left eye. When he experienced respiratory difficulty he was diagnosed to have an ameloblastoma in left nostril requiring surgery. Gorlin syndrome is an autosomal dominant condition characterized by basal cell carcinomas, and skeletal and neurological anomalies. The presence of multiple basal cell carcinomas on the eyelids in a child or in a young patient should alert ophthalmologists to the possibility of this syndrome.


Arterial impulse model for the BOLD response to brief neural activation.
The blood oxygen level dependent (BOLD) signal evoked by brief neural stimulation, the hemodynamic response function (HRF), is a critical feature of neurovascular coupling. The HRF is directly related to local transient changes in oxygen supplied by cerebral blood flow (CBF) and oxygen demand, the cerebral metabolic rate of oxygen (CMRO2). Previous efforts to explain the HRF have relied upon the hypothesis that CBF produces a non-linear venous dilation within the cortical parenchyma. Instead, the observed dynamics correspond to prompt arterial dilation without venous volume change. This work develops an alternative biomechanical model for the BOLD response based on the hypothesis that prompt upstream dilation creates an arterial flow impulse amenable to linear description. This flow model is coupled to a continuum description of oxygen transport. Measurements using high-resolution fMRI demonstrate the efficacy of the model. The model predicts substantial spatial variations of the oxygen saturation along the length of capillaries and veins, and fits the varied gamut of measured HRFs by the combined effects of corresponding CBF and CMRO2 responses. Three interesting relationships among the hemodynamic parameters are predicted. First, there is an offset linear correlation with approximately unity slope between CBF and CMRO2 responses. Second, the HRF undershoot is strongly correlated to the corresponding CBF undershoot. Third, late-time-CMRO2 response can contribute to a slow recovery to baseline, lengthening the HRF undershoot. The model provides a powerful mathematical framework to understand the dynamics of neurovascular and neurometabolic responses that form the BOLD HRF.


Comparison of cestode antigens in an enzyme-linked immunosorbent assay for the diagnosis of Echinococcus granulosus, Taenia hydatigena and T ovis infections in sheep.
Nine antigens, prepared from somatic tissue, cyst fluids or produced during in vitro culture of Echinococcus granulosus, Taenia hydatigena, T ovis or T crassiceps were tested for their suitability for the diagnosis of larval cestode infections in sheep by the enzyme-linked immunosorbent assay (ELISA). The sensitivity and specificity of each of these antigens were assessed using sera from sheep experimentally infected with graded monospecific infections of E granulosus, T hydatigena or T ovis eggs and sera from naturally infected aged sheep. The ability of eight of the antigens to detect the antibody response to larval cestode infection was also compared over 12 months using sera from serial bleedings. Using the ELISA, all of the antigens were able to detect the presence of larval cestodes, even in sheep with only one or two cysts. Over 12 months, the antibody responses were not generally statistically related to the total number of cysts present in the animals. None of the antigens was able to detect specific infections only. The antigen with least non-specific background activity, which consistently detected the highest antibody titres in the sera of all infected animals was the secretion from T ovis worms cultured in vitro, and is, therefore, the antigen of choice for the detection of non-specific infections with larval cestodes in sheep.


Effect of psychotherapy on recurrence of events and quality of life in patients with vasovagal syncope.
Emotional distress is related to recurrence of syncope compromising patient's quality of life (QoL). The aim of this study was to determine if weekly sessions of psychotherapy reduce recurrence of events and improve QoL by SF-36 among patients with refractory vasovagal syncope. A randomised controlled pilot trial including 10 patients with recurrent vasovagal syncope and positive tilt table test was conducted. Known cardiac disease and ongoing psychotherapeutic interventions were the main exclusion criteria. All patients received standard of care treatment. Additionally, after randomisation, half of the patients underwent weekly sessions of psychotherapy for 12 months. Analysis of recurrence of events and QoL showed no significant change in the control group but, in the intervention group, there was a significant reduction in the rate of near-syncope episodes per month (5.7 ± 1.4 × 1.7 ± 1.0; P < 0.01), syncope in 1 year (4.6 ± 0.9 × 1.0 ± 0.7; P < 0.01) and a significant improvement in the overall assessment of QoL (44.1 ± 10.0 vs. 70.3 ± 10.3, P < 0.01). In conclusion, patients with refractory vasovagal syncope undergoing regular psychotherapeutic intervention had less recurrence of events and improved their quality of life in 1 year.Trial Registration: ClinicalTrials.gov number, NCT04252729.


Coordination-driven self-assembly of supramolecular cages: heteroatom-containing and complementary trigonal prisms.
The self-assembly of three nanoscopic prisms of approximate size 1 x 4 nm is reported. Tetrahedral carbon, silicon, and phosphorus were used as structure-defining elements in these coordination-based cages. A carbon-based assembly completes a pair of nanoscopic complementary 3-D structures. The formation of the structures is supported by multinuclear NMR, ESI FT-ICR mass spectrometry, and elemental analysis data.


Minimally Invasive Glaucoma Surgery-to Remove or Preserve the Trabecular Meshwork: That is the Question?
How to cite this article: Dada T, Mahalingam K, Bhartiya S. Minimally Invasive Glaucoma Surgery-to Remove or Preserve the Trabecular Meshwork: That is the Question? J Curr Glaucoma Pract 2021;15(2):47-51.


Mutations affecting the ability of the Escherichia coli UmuD' protein to participate in SOS mutagenesis.
The products of the SOS-regulated umuDC operon are required for most UV and chemical mutagenesis in Escherichia coli, a process that results from a translesion synthesis mechanism. The UmuD protein is activated for its role in mutagenesis by a RecA-facilitated autodigestion that removes the N-terminal 24 amino acids. A previous genetic screen for nonmutable umuD mutants had resulted in the isolation of a set of missense mutants that produced UmuD proteins that were deficient in RecA-mediated cleavage (J. R. Battista, T. Ohta, T. Nohmi, W. Sun, and G. C. Walker, Proc. Natl. Acad. Sci. USA 87:7190-7194, 1990). To identify elements of the UmuD' protein necessary for its role in translesion synthesis, we began with umuD', a modified form of the umuD gene that directly encodes the UmuD' protein, and obtained missense umuD' mutants deficient in UV and methyl methanesulfonate mutagenesis. The D39G, L40R, and T51I mutations affect residues located at the UmuD'2 homodimer interface and interfere with homodimer formation in vivo. The D75A mutation affects a highly conserved residue located at one end of the central strand in a three-stranded beta-sheet and appears to interfere with UmuD'2 homodimer formation indirectly by affecting the structure of the UmuD' monomer. When expressed from a multicopy plasmid, the L40R umuD' mutant gene exhibited a dominant negative effect on a chromosomal umuD+ gene with respect to UV mutagenesis, suggesting that the mutation has an effect on UmuD' function that goes beyond its impairment of homodimer formation. The G129D mutation affects a highly conserved residue that lies at the end of the long C-terminal beta-strand and results in a mutant UmuD' protein that exhibits a strongly dominant negative effect on UV mutagenesis in a umuD+ strain. The A30V and E35K mutations alter residues in the N-terminal arms of the UmuD'2 homodimer, which are mobile in solution.


Magnetic fingerprint of individual Fe4 molecular magnets under compression by a scanning tunnelling microscope.
Single-molecule magnets (SMMs) present a promising avenue to develop spintronic technologies. Addressing individual molecules with electrical leads in SMM-based spintronic devices remains a ubiquitous challenge: interactions with metallic electrodes can drastically modify the SMM's properties by charge transfer or through changes in the molecular structure. Here, we probe electrical transport through individual Fe4 SMMs using a scanning tunnelling microscope at 0.5 K. Correlation of topographic and spectroscopic information permits identification of the spin excitation fingerprint of intact Fe4 molecules. Building from this, we find that the exchange coupling strength within the molecule's magnetic core is significantly enhanced. First-principles calculations support the conclusion that this is the result of confinement of the molecule in the two-contact junction formed by the microscope tip and the sample surface.


Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ).
Follicular lymphoma is the most common form of lymphoma in Europe and the USA. In this prospective, single-arm, open-labelled, multicentre non-randomised phase II trial (FLUMIZ [FLUdarabine, MItoxantrone, Zevalin] trial) we aimed to assess the efficacy and safety of fludarabine and mitoxantrone plus radioimmunotherapy in untreated patients with follicular non-Hodgkin lymphoma (NHL). Patients with stage III or IV untreated indolent follicular NHL were enrolled between June 1, 2004, and April 15, 2006, at 13 Italian institutions, and were treated with oral fludarabine (40 mg/m2 on days 1 to 3) and intravenous mitoxantrone (10 mg/m2 on day 1) every 28 days for six cycles. Patients who had at least a partial response (PR) with normal platelet counts (>100x10(9)/L) and granulocyte counts (1.5x10(9)/L), and bone-marrow infiltration less than 25% 4-6 weeks after completion of the sixth cycle of chemotherapy were deemed eligible for consolidation treatment 6-10 weeks after the sixth cycle with one course of yttrium-90 ((90)Y)-labelled ibritumomab tiuxetan (Zevalin), which consisted of an initial infusion of intravenous rituximab (250 mg/m2) on day 1 followed by a second 250 mg/m2 infusion on day 7, 8, or 9. The second infusion was followed by a weight-based dose of 90Y-ibritumomab tiuxetan, administered as a slow intravenous push over 10 min. Primary endpoints were complete response (CR) and haematological toxic effects and secondary endpoints were overall survival and progression-free survival. Responses were classified according to the International Workshop for Response Criteria for non-Hodgkin's lymphomas. Analysis was per protocol. This trial is registered as a European Standard Controlled Trial on the EudraCT website http://oss-sper-clin.agenziafarmaco.it, number 2004-002211-92. 61 patients were enrolled in the trial and received six cycles of fludarabine and mitoxantrone, after which an overall response was noted in 98% (60 of 61) of patients (43 of 61 patients had CR and 17 of 61 patients had PR). 57 patients (43 with CR and 14 with PR) were deemed eligible for subsequent (90)Y-ibritumomab tiuxetan. Of the 14 patients who had PR after the initial treatment, 12 obtained CR after (90)Y-ibritumomab tiuxetan. By the end of the entire treatment regimen 55 of 57 patients achieved CR. With a median follow-up of 30 months (range 21-48), 3-year progression-free survival was estimated to be 76% (95% CI 72.3-82.4) and 3-year overall survival 100%. 36 of 57 patients had grade 3 or 4 haematological toxic effects, and blood transfusions were given to 21 of 57 patients. This trial has provided evidence for the feasibility, tolerability, and efficacy of fludarabine and mitoxantrone plus (90)Y-ibritumomab tiuxetan in untreated patients with follicular NHL.


Hypothalamic Regulation of Obesity.
Obesity has now reached pandemic proportions and represents a major socioeconomic and health problem in our societies [...].


Single-fraction proton beam stereotactic radiosurgery for cerebral arteriovenous malformations.
To evaluate the obliteration rate and potential adverse effects of single-fraction proton beam stereotactic radiosurgery (PSRS) in patients with cerebral arteriovenous malformations (AVMs). From 1991 to 2010, 248 consecutive patients with 254 cerebral AVMs received single-fraction PSRS at our institution. The median AVM nidus volume was 3.5 cc (range, 0.1-28.1 cc), 23% of AVMs were in critical/deep locations (basal ganglia, thalamus, or brainstem), and the most common prescription dose was 15 Gy(relative biological effectiveness [RBE]). Univariable and multivariable analyses were performed to assess factors associated with obliteration and hemorrhage. At a median follow-up time of 35 months (range, 6-198 months), 64.6% of AVMs were obliterated. The median time to total obliteration was 31 months (range, 6-127 months), and the 5-year and 10-year cumulative incidence of total obliteration was 70% and 91%, respectively. On univariable analysis, smaller target volume (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.86-0.93, P<.0001), smaller treatment volume (HR 0.93, 95% CI 0.90-0.96, P<.0001), higher prescription dose (HR 1.16, 95% CI 1.07-1.26, P=.001), and higher maximum dose (HR 1.14, 95% CI 1.05-1.23, P=.002) were associated with total obliteration. Deep/critical location was also associated with decreased likelihood of obliteration (HR 0.68, 95% CI 0.47-0.98, P=.04). On multivariable analysis, critical location (adjusted HR [AHR] 0.42, 95% CI 0.27-0.65, P<.001) and smaller target volume (AHR 0.81, 95% CI 0.68-0.97, P=.02) remained associated with total obliteration. Posttreatment hemorrhage occurred in 13 cases (5-year cumulative incidence of 7%), all among patients with less than total obliteration, and 3 of these events were fatal. The most common complication was seizure, controlled with medications, both acutely (8%) and in the long term (9.1%). The current series is the largest modern series of PSRS for cerebral AVMs. PSRS can achieve a high obliteration rate with minimal morbidity. Post-treatment hemorrhage remains a potentially fatal risk among patients who have not yet responded to treatment.


Embolisation of silicone rubber catheters used for intravenous feeding; a preventable complication.
The advantages of silicone rubber central venous catheters are widely recognised, but embolisation of the whole catheter can occur due to malfunction of the hub which is used to clamp the catheter to the female luer connector. Two cases are described in which silicone rubber catheters were successfully removed from the heart using percutaneous techniques. A modification is suggestion to prevent this complication.


'Make the Most of the Situation'. Older Adults' Experiences during COVID-19: A Longitudinal, Qualitative Study.
The COVID-19 pandemic restrictions have been associated with increased social isolation and reduced participation in older adults. This longitudinal qualitative study drew on life course theory to analyse data from a series of four sequential semi-structured interviews conducted between May 2020-February 2021 with adults aged 65+ (n = 12) to explore older adults' experiences adjusting to the COVID-19 pandemic. We identified three themes: (1) Struggling 'You realize how much you lost' describes how older adults lost freedoms, social connections and activities; (2) Adapting 'whatever happens, happens, I'll do my best', revealing how older adults tried to maintain well-being, participation and connection; and (3) Appreciating 'enjoy what you have', exploring how older adults found pleasure and contentment. Engagement in meaningful activities and high-quality social interactions supported well-being during the COVID-19 pandemic for older adults. This finding highlights the need for policies and services to promote engagement during longstanding global crises.


Effects of exercise tolerance, age, and gender on the specificity of radionuclide angiography: sequential ejection fraction analysis during multistage exercise.
We investigated the factors that determine the left ventricular ejection fraction response to exercise in 57 middle-aged, untrained patients with angiographically normal coronary arteries. The ejection fraction was measured by blood pool radionuclide angiography during each stage of exercise. Stepwise regression analysis was applied to 39 variables, and the resulting significant variables were then included in a logistic regression model to determine which of them would predict a normal ejection fraction response. By stepwise regression analysis, the best model (F = 5.6, p = 0.0004) was obtained by combining four variables: achieving 85% of maximal predicted heart rate, peak heart rate, number of exercise stages performed, and resting pulse pressure. Only the latter two variables were significant by logistic regression analysis. The specificity of greater than or equal to 5 ejection fraction unit increase at peak exercise was 42%, 75%, and 100% in patients who exercised one, two, or three stages, respectively. Furthermore, the increase in ejection fraction during each exercise stage was independent of age or gender. Thus the standard criteria of normality during exercise radionuclide angiography have high specificity only when applied to patients with good exercise performance, regardless of age or gender.


Bilharzial role in staging bladder carcinoma histopathological-transurethral sonography and computerized tomography.
Bilharzial bladder tumour of 28 patients staged pre-operatively by transurethral ultrasound and computerized tomography (CT). The accuracy varied from 66.6% to 77.7% in different stages as compared with pathological stage. The bilharzial reaction could be play a role in this accuracy and the histopathological study is the accurate way to express the depth of infiltration of the tumour in the bladder wall as well as the depth of vascular invasion which may be greater than the primary tumour itself.


Thermoactive Smart Electrospun Nanofibers.
The recent burst of research on smart materials is a clear evidence of the growing interest of the scientific community, industry, and society in the field. The exploitation of the great potential of stimuli-responsive materials for sensing, actuation, logic, and control applications is favored and supported by new manufacturing technologies, such as electrospinning, that allows to endow smart materials with micro- and nanostructuration, thus opening up additional and unprecedented prospects. In this wide and lively scenario, this article systematically reviews the current advances in the development of thermoactive electrospun fibers and textiles, sorting them, according to their response to the thermal stimulus. Hence, several platforms including thermoresponsive systems, shape memory polymers, thermo-optically responsive systems, phase change materials, thermoelectric materials, and pyroelectric materials, are described and critically discussed. The difference in active species and outputs of the aforementioned categories is highlighted, evidencing the transversal nature of temperature stimulus. Moreover, the potential of novel thermoactive materials are pointed out, revealing how their development could take to utmost interesting achievements.


Physical activity, self-efficacy, and quality of life in multiple sclerosis.
Quality of life (QOL) is compromised among individuals with multiple sclerosis (MS). Self-efficacy and physical activity have been positively associated with QOL in persons with MS, and based on a social cognitive perspective, the relationship between physical activity and QOL might be indirect and accounted for by self-efficacy. We tested the hypothesis that physical activity would be indirectly associated with QOL through a pathway that included self-efficacy. Participants were 133 individuals with a definite diagnosis of MS who completed the Godin Leisure-Time Exercise Questionnaire, Multiple Sclerosis Self-Efficacy scale, and Multiple Sclerosis Impact Scale. Path analysis indicated that those with MS who were more physically active had greater self-efficacy for function and control, and self-efficacy for function and control were associated with greater physical and psychological components of QOL. Our findings support physical activity as a possible modifiable behavior for mitigating reductions of QOL by improving self-efficacy in individuals with MS.


Expression of Lipoprotein associated phospholipase A2 enzyme in medical undergraduate students with metabolic syndrome.
Metabolic syndrome (MS) and atherosclerosis are chronic inflammatory conditions. Lipoprotein-associated phospholipase A2 (LpPLA2) is a circulatory marker of systemic inflammation and a risk predictor for cardiovascular diseases. This study aims to evaluate the expression of this enzyme in an effort to understand the underlying mechanism of atherosclerosis in MS. This study included twenty patients of MS and same number of healthy controls. Anthropometry and clinical examination were carried out in both groups. Real time PCR was performed for LpPLA2 mRNA and relative expression was calculated using ΔΔCT method keeping β2 microglobin and β-actin as internal controls. LpPLA2 mRNA expression was higher in patients of MS. Fold change was 5.7 when β2 microglobin was used as normaliser and 4.97 when β-actin was used. mRNA levels of LpPLA2 correlated significantly with waist circumference (r=0.462, p=0.003) and systolic blood pressure (r=0.392, p=0.015) as well as high density lipoprotein cholesterol (r=-0.453, p=0.003). High expression of LpPLA2 mRNA indicates that systemic inflammation has role in pathogenesis of atherosclerosis in patients of MS. This is evident from its direct correlation with blood pressure. The study also suggests that expression of LpPLA2 may be associated with obesity. Therefore, LpPLA2 mRNA expression levels may develop as an important risk predictor for vascular complications in MS.


A simple electromagnetic mechanical stimulator for electrophysiological recording in man.
In order to study peripheral nervous signals in response to a noxious or innocuous mechanical cutaneous stimulus we deviced an electromechanical stimulator of which stimulus duration, response frequency and delay are perfectly controlled. Using this device, stimulation of the finger has allowed us to record electrophysiological responses over the course of the median nerve.


Association of hepatitis C virus carrier state with the occurrence of hepatitis C virus core antibodies.
An enzyme immunoassay (EIA) was developed for the determination of antibodies against the "putative" core protein of hepatitis C virus (HCV). Antigens used were recombinant fragments (amino acids 6-77 or 6-143) of the HCV core protein, produced in Escherichia coli with truncated hepatitis B core (HBc) as fusion protein. Evaluation of 385 sera positive for HCV antibodies by first generation EIA, revealed 98 (25.4%) with HCV core antibodies. HCV-RNA, determined by the polymerase chain reaction (PCR), was exclusively found in the sera positive for HCV core antibodies (89 PCR positives). In random screening of 3,708 sera, 3 sera with HCV core antibodies were found PCR positive. Only 2 of these sera were positive in the first generation EIA. It is concluded that HCV core antibody determination is a reliable test for identifying HCV carriers among blood donors.


Using self-organizing maps to infill missing data in hydro-meteorological time series from the Logone catchment, Lake Chad basin.
Hydro-meteorological data is an important asset that can enhance management of water resources. But existing data often contains gaps, leading to uncertainties and so compromising their use. Although many methods exist for infilling data gaps in hydro-meteorological time series, many of these methods require inputs from neighbouring stations, which are often not available, while other methods are computationally demanding. Computing techniques such as artificial intelligence can be used to address this challenge. Self-organizing maps (SOMs), which are a type of artificial neural network, were used for infilling gaps in a hydro-meteorological time series in a Sudano-Sahel catchment. The coefficients of determination obtained were all above 0.75 and 0.65 while the average topographic error was 0.008 and 0.02 for rainfall and river discharge time series, respectively. These results further indicate that SOMs are a robust and efficient method for infilling missing gaps in hydro-meteorological time series.


A composite hydrogel membrane with shape and water retention for corneal tissue engineering.
Tissue engineering (TE) cornea is one of the most potential alternatives to the shortage of corneal donors in cornea transplantation. Sodium alginate (SA) hydrogel is commonly used as scaffold in TE. Herein, we present an approach to construct a composite hydrogel, which with SA fiber skeleton structure for shape retention and gelatin surface modification for water retention. The light transmittance, water retention rate, and swelling rate of hydrogels were characterized, and the tensile mechanical properties were also investigated. Keratinocytes were treated with material extract liquor and the results showed that the gelatin modified SA hydrogel has good cytocompatibility. Furthermore, human corneal stromal fibroblasts (HCSFs) from the lenticules were implanted on the surface of gels, and the SA-gelatin hydrogel significantly improved the adhesion and spreading of HCSFs. Finally, we discussed the improvement and application prospect of the composite hydrogel as cornea equivalents.


Right ventricular performance during left ventricular unloading conditions: the contribution of the right ventricular free wall.
Right ventricular (RV) dysfunction is a significant complication following implantation of left ventricular assist device (LVAD). However, RV performance after LVAD implantation remains unclear. We have studied the effects of preload and afterload on RV performance under left ventricular (LV) unloading. Six adult mongrel dogs were subjected to cardiopulmonary bypass. RV preload and afterload were independently regulated. Dynamic pressure-length analysis of RV free walls was performed using micromanometer catheter and sonomicrometric dimension transducers. Global RV systolic function was evaluated by the relationship between stroke volume vs. end-diastolic length (EDL) or end-diastolic pressure (EDP). We also examined the afterload dependency of RV performance at constant stroke volume. Stroke volume vs. EDP and stroke volume vs. EDL demonstrated a linear relationship (r(2) = 0.849 +/- 0.147 and 0.776 +/- 0.121, respectively). At constant stroke volume, RV systolic peak pressure vs. EDL or EDP were shown to have a linear relationship (r(2) = 0.906 +/- 0.050 vs. 0.909 +/- 0.047, respectively). The Frank-Starling relationship for RV performance was shown in this animal model. Without interventricular interaction, RV preload is dependent on RV afterload.


[Prognostic factors in IgG and micromolecular multiple myeloma. Retrospective analysis of 50 consecutive cases].
Clinico-pathological findings in 50 consecutive previously untreated patients with IgG and micromolecular multiple myeloma were reviewed. The clinical factors related with a shorter survival were: Bence-Jones proteinuria, high level of serum creatinine and serum calcium, low level of haemoglobin, widespread bone lesions, and plasma cell percentage in bone marrow more than 20%. This factor is significantly correlated with survival. The staging systems proposed by Durie and Salmon and by Merlini et al. are a precious reference in the evaluation of survival and treatment.


Multiplex and visual detection of African Swine Fever Virus (ASFV) based on Hive-Chip and direct loop-mediated isothermal amplification.
African swine fever is caused by African swine fever virus (ASFV), and has a mortality rate approaching 100%. It has already caused tremendous economy lost around the world. Without effective vaccine, rapid and accurate on-site detection plays an indispensable role in controlling outbreaks. Herein, by combining Hive-Chip and direct loop-mediated isothermal amplification (LAMP), we establish a multiplex and visual detection platform. LAMP primers targeting five ASFV genes (B646L, B962L, C717R, D1133L, and G1340L) were designed and pre-fixed in Hive-Chip. On-chip LAMP showed the limits of detection (LOD) of ASFV synthetic DNAs and mock samples are 30 and 50 copies per microliter, respectively, and there is no cross-reaction among the target genes. The overall performance of our platform is comparable to that of the commercial kits. From sample preparation to results readout, the entire process takes less than 70 min. Multiplex detection of real samples of ASFV and other swine viruses further demonstrates the high sensitivity and specificity of Hive-Chip. Overall, our platform provides a promising option for on-site, fast and accurate detection of ASFV.


Experimental arena size alters larval zebrafish photolocomotor behaviors and influences bioactivity responses to a model neurostimulant.
Zebrafish behavior is increasingly common in biomedical and environmental studies of chemical bioactivity. Multiple experimental arena sizes have been used to measure photolocomotion in zebrafish depending on age, endpoints observed, and instrumentation, among other factors. However, the extent to which methodological parameters may influence naïve behavioral performance and detection of behavioral changes is poorly understood. Here we measured photolocomotion and behavioral profiles of naïve larval zebrafish across arena sizes. We then performed concentration response studies with the model neurostimulant caffeine, again across various arena dimensions. We found total swimming distance of unexposed fish to increase logarithmically with arena size, which as related to circumference, area, and volume. Photomotor response during light/dark transitions also increased with arena size. Following caffeine exposure, total distance travelled was significantly (p < 0.001) affected by well size, caffeine treatment (p < 0.001), and the interaction of these two experimental factors (p < 0.001). In addition, behavioral response profiles showed differences between 96 well plates and larger well sizes. Biphasic response, with stimulation at lower concentrations and refraction at the highest concentration, was observed in dark conditions for the 96 well size only, though almost no effects were identified in the light. However, swimming behavior was significantly (p < 0.1) altered in the highest studied caffeine treatment level in larger well sizes during both light and dark periods. Our results indicate zebrafish swim more in larger arenas and arena size influences behavioral response profiles to caffeine, though differences were mostly observed between very small and large arenas. Further, careful consideration should be given when choosing arena size, because small wells may lead to restriction, while larger wells may differentially reflect biologically relevant effects. These findings can improve comparability among experimental designs and demonstrates the importance of understanding confounding methodological variables.


A mutation in human immunodeficiency virus reverse transcriptase and decline in CD4 lymphocyte numbers in long-term zidovudine recipients.
A nested polymerase chain reaction assay was used to define the sequence of a specific codon, amino acid 215, of the human immunodeficiency virus (HIV) pol gene in DNA from peripheral blood mononuclear cells (PBMC) and viral RNA from serum from 38 patients treated with zidovudine for > or = 2 years. After treatment for a mean of 34 months, 17 patients with sequences with a codon 215 mutation had a mean 50% decrease in CD4 cells, compared with 21 patients with sequences wild-type at codon 215, who had a mean 11% increase in CD4 cells (P < .0001). Patients with a mutation at 215 had a ninefold higher provirus burden in PBMC. Detection of the codon 215 mutation in plasma viral RNA preceded detection of the mutation in DNA from PBMC and decline in CD4 cells. The appearance of a mutation at codon 215 in the HIV reverse transcriptase gene in patients receiving zidovudine may be a marker for impending immunologic decline.


Hetisine-type diterpenoid alkaloids from the Bhutanese medicinal plant Aconitum orochryseum.
Investigation of Aconitum orochryseum, a Bhutanese traditional medicine ("gSo-ba Rig-pa") plant locally known as "Bong-kar", resulted in the isolation of three new hetisine-type diterpenoid alkaloids, named orochrine (1), 2-O-acetylorochrine (2), and 2-O-acetyl-7alpha-hydroxyorochrine (3), together with the previously reported alkaloids atisinium chloride (4) and virescenine (5). The structures of the new alkaloids were elucidated by spectroscopic data analysis.


MRA of the Supraaortic Vasculature: Comparison of Gadobutrol and Gadoterate Meglumine at 1.5 T.
Gadobutrol (GB) and gadoterate meglumine (GM) are contrast agents used for contrast-enhanced magnetic resonance angiography (CEMRA). Supraaortic vasculature (SAV) CEMRAs are used to evaluate stroke risk and neurologic symptoms. There is a need to compare the SAV CEMRA image quality obtained with GB and GM. To intra-individually compare MRA images obtained with equimolar GB and GM at 1.5 T in the SAV. Prospective, crossover. Twenty-eight subjects (54 ± 13 years; 17 female). 1.5 T; three-dimensional (3D) gradient recalled echo. Quantitative image quality was measured by normalized signal intensity (SIn ) [SIn = SI blood/SD blood] and contrast ratio (CR) [CR = SI blood/SI muscle], determined by an observer (JWC) with 1 year of vascular imaging experience. Three radiologists (AS, PA, and MU) with (5, 5, and 6 years of) vascular imaging experience evaluated image quality by Likert-scale ratings (of image impression, wall conspicuity, and artifact absence). SIn and CR were compared with paired t-tests or Wilcoxon signed-rank tests and Bland-Altman plots. Qualitative ratings were compared with Wilcoxon signed-rank test. No significant difference in SIn was found between GB and GM. CRs with GB were significantly higher than GM at the right common carotid (6.9 ± 2.5 vs. 4.8 ± 1), left internal carotid (7.3 ± 2 vs. 4.4 ± 1.2), right internal carotid (7.7 ± 2.2 vs. 5 ± 1.1), and left vertebral (6.6 ± 2.2 vs. 4.5 ± 1.1) arteries. Bland-Altman plots showed relatively greater differences between GB and GM at higher CRs and SIn s. GM showed significantly higher artifact than GB (3.56 ± 0.52 vs. 3.36 ± 0.46) and significantly lower overall image quality (10.73 ± 1.45 vs. 11.26 ± 1.58) at the left vertebral artery. At 1.5 T and equimolar demonstration, GB (0.1 mL/kg, i.e., 0.1 mmol/kg) showed higher CRs in the SAV compared to GM (0.2 mL/kg, i.e., 0.1 mmol/kg) at most vessels. Subjective image quality was not significantly different between the two agents for most vessels. 2 TECHNICAL EFFICACY: Stage 2.


Foot involvement in systemic sclerosis: a longitudinal study of 100 patients.
To investigate the clinical and radiologic features of foot involvement in systemic sclerosis (SSc). One hundred patients (91 women, 9 men; mean age, 51.9 +/- 11 years) with SSc (mean disease duration, 17.4 +/- 10.5 years) were retrospectively studied. Seventy-four subjects had limited scleroderma and 26 diffuse scleroderma. Radiologic changes of foot involvement were assessed at presentation (time of diagnosis) and follow-up ranging from 1 to 28 years (median range, 7 years) and were compared with changes detected in the hands of each patient at the same presentation and follow-up. Correlations with skin and internal organ involvement were assessed. Ninety patients had foot involvement clinically. Forty-three had it at initial evaluation; 47 developed it during follow-up. Median time to clinical event occurrence was 10 years (95% CI, 6.7-13.3) with 44% censored case probability at this time. The onset of clinically evident foot involvement was later in limited SSc than in diffuse SSc. In comparison with hands with SSc, feet with SSc had lower rates of necrotizing Raynaud's phenomenon and tendon friction rubs and decreased skin thickening scores, whereas arthralgias occurred significantly more often. At presentation, 37 patients had radiologic abnormalities of their feet compared with 69 of their hands (P <.001); the hands had a significantly higher prevalence of acroosteolysis (P <.001). At the end of the follow-up, 35 of 50 SSc patients had radiographic foot involvement compared with 50 of 51 with hand involvement (P <.001). A significantly higher prevalence of acroosteolysis (P <.001), calcinosis (P <.05), and erosions (P <.05) of the hands were detected at that time. This study shows that compared with hand involvement in SSc, foot involvement in SSc has a later onset and is relatively less frequent but can be disabling.


p53, p16 and cyclin D1: molecular determinants of radiotherapy treatment response in oral carcinoma.
Management of oral cancer by radiotherapy has witnessed promising advances in the past few years, with patient-tailored radio fractionation regimens. Different fractionation schedules, conventional and altered regimes, have been used in curative radiotherapy. Although contribution of biological markers on radio response has been evaluated, its unique influence on various radio fractionation schemes has not been accounted so far. Our study analyses a set of proteins that previously demonstrated radio response influence for their possible prognostic value in decision-making process between the respective fractionation schemes. Expression patterns of regulatory proteins such as p53, cyclin D1, p16, Cdk4, p21, Rb, bcl-2 and PCNA were determined by immunohistochemistry utilizing monoclonal antibodies in 125 patients who received curative radiotherapy dose. Among these 125 patients, 90 (72%) received altered fractionation, whereas 35 (28%) received conventional fractionation. p53 over-expression correlated with local treatment failure among the patients treated with conventional fractionation whereas cyclin D1 over-expression and p16 underexpression were associated with local treatment failure as well as overall survival in altered fractionation treated cases. Our findings suggest that wild-type p53 status may be an important parameter for achieving high local control in those patients undergoing conventional fractionation, where as intact p16 and cyclin D1 status may be beneficial for effective local control in patients who are treated with altered fractionation. Furthermore, it can be assumed that conventional fractionation employs p53-mediated apoptosis, whereas altered fractionation activates the functional G1 cell-cycle checkpoint for tumor growth suppression.


Kinetic studies on the reaction catalyzed by DNA ligase from calf thymus.
Kinetic analysis of the reaction catalyzed by calf thymus DNA ligase (EC 18.104.22.168) has been carried out using [5'-32P]nicked DNA as substrate. The results of initial velocity and product inhibition studies indicate that the ligase reaction is likely to proceed through the 'uni-uni uni-bi ping-pong' mechanism. The order of substrate addition and product release is as follows: ATP, PPi, nicked DNA, sealed DNA and 5'-AMP. The true Km values for ATP and for nicked DNA (5'-phosphoryl ends) were 2 microM and 0.11 microM, respectively. The turnover number was estimated to be 7 sealing events per min. dATP was an inhibitor competitive with ATP (Ki = 25 microM). The addition of 0.5 mM spermine or 5 mM spermidine resulted in an increase in the apparent Km for nicked DNA as well as in the apparent V, whereas 0.1 M KCl increased only the apparent Km for nicked DNA. Neither polyamine nor KCl affected the apparent Km for ATP. The ligase reaction was not significantly affected by aphidicolin and various phosphate compounds tested.


Iliac artery stent placement: clinical experience with a nitinol stent.
To determine the effectiveness of a prototype nitinol stent in the iliac arteries. Fourteen patients with arteriosclerotic lesions of the iliac arteries (nine stenoses, five occlusions) were treated percutaneously with a prototype nitinol vascular stent (Cragg stent) after unsuccessful percutaneous transluminal angioplasty. In 13 patients available for follow-up, the mean ankle-brachial index (ABI) increased from 0.4 +/- 0.32 (standard deviation) before the procedure to 0.81 +/- 0.27 after the procedure (P < .01). After 6, 12, and 24 months, the mean ABI was 0.97 +/- 0.2, 0.87 +/- 0.15, and 0.89 +/- 0.1, respectively. In two patients, radial stiffness of the stent was too low to completely eliminate a high-grade, calcified stenosis; long-term patency of the vessel, however, was preserved. In all other patients, stent placement achieved good vascular reconstitution. No stent occlusion or restenosis was observed. The results with the Cragg stent were similar to those with other commercially available stents. These preliminary results require confirmation with a larger series.


[Association of obesity and insulin resistance with serum testosterone, sex hormone binding globulin and estradiol in older males].
There is an increased accumulation of fat tissue with subsequent increase of insulin level, insulin resistance and decrease of testosterone level in aging males. Assessment of the relations between obesity, insulin resistance and levels of sex hormones. Indices of obesity (BMI, WHR, waist circumference), insulin level, insulin resistance (HOMA-IR) and levels of sex hormones (total testosterone, free testosterone, free testosterone index, sex hormone-binding globulin--SHBG, estradiol) were measured in 107 males at the mean age of 60.1 +/- 7 years. Obesity among aging males is associated with insulin resistance and hyperinsulinism. All above factors correlate with decreased serum levels of testosterone and sex hormone binding globulin as well as increased ratio estradiol/testosterone ratio. Our data suggest a role of decreased levels of testosterone and SHBG in pathogenesis of visceral obesity and metabolic syndrome in older males.


Stimulating creativity in all elders: a continuum of interventions.
Contemporary society seldom associates creativity with people in later adult years. We challenge that perception. A continuum of creative programs defined here shows promise for eliciting late life creativeness offering elders in the community, in residential settings, in adult day care, and in home care new avenues for expression. Life story writing and sharing groups, Visible Lives storyboards, and TimeSlips storytelling method for patients with dementia equip caregivers with new tools to nourish creativity in all elders. Evidence suggests that stimulating creativity in elders at all levels of functioning improves health outcomes. This article introduces programs designed to engage, encourage, and inspire elders regardless of functionality. All three related but discreet interventions share core components of listening with intention, utilizing positive affirmation, and facilitating sharing in community as participants develop surprising new capabilities. Health care providers, community volunteers, and family members can develop skills and techniques to implement any of the programs described. Fostering creative expression through cognitive exercise and imagination among those in later years may forestall dementias, improve quality of life for elders and their caregivers, and meet unmet personal and societal needs. These programs demonstrate the possibility of growth and creative potential at every stage in life, including the latest years, even for those with dementias.


Understanding the speech-understanding problems of older adults.
The purpose of this article was to review recent research from our laboratory on the speech-understanding problems of older adults. The method involved a narrative review of previously reported data from our laboratory. To date, the results from most of our studies have indicated that peripheral and cognitive factors are the primary contributors to the speech-understanding problems of older adults, with the relative mix of these 2 factors changing for unaided (primarily peripheral) and aided (primarily cognitive) listening conditions.


Clinical features and mutation analysis of X-linked agammaglobulinemia in 20 Chinese patients.
X-linked agammagobulinemia (XLA) is a primary immunodeficiency caused by Bruton's tyrosine kinase (BTK) gene mutation. XLA patients have an extremely small amount of peripheral B cells and profound deficiency in all immunoglobulin isotypes. We analyzed the clinical, immunologic, and molecular characteristics of children with XLA in an attempt to improve the diagnosis and treatment of XLA in China. Twenty children with XLA-compatible phenotypes from 18 unrelated families were enrolled in this study. The BTK gene was amplified and sequenced, followed by mutation analysis in these children and their female relatives. Eighteen different mutations of the BTK gene were identified in the 20 patients. Eleven mutations had been reported previously including eight missense mutations (c.994C>T, c.1987C>A, c.1885G>T, c.502T>C, c.1085C>T, c.1816C>T, c.214C>T, c.1912G>A) and three nonsense mutations (c.1267T>A, c.1793C>G, c.1618C>T). Seven novel mutations of the BTK gene were also presented and included five missense mutations (c.134T>A, c.1646T>A, c.1829C>G, c.711G>T, c.1235G>A), one splice-site mutation (c.523+1G>A) and one insertion mutation (c.1024-1025in sTTGCTAAAGCAACTGCTAAAGCAAG). Eight out of 18 mutations of the BTK gene were located in the TK domain, 4 in the PH domain, 4 in the SH2 domain and 2 in the TH domain. Genetic study for carrier status was carried out in 18 families with definite BTK gene mutations. Nine carriers with BTK gene mutations were identified. Six families without carriers were detected, and 3 patients were not tested in this study. Our results support that molecular genetic testing represents an important tool for early confirmed diagnosis of congenital agammaglobulinemia and may allow accurate carrier detection and prenatal diagnosis.


Reply letter to "Vaccine effectiveness of recombinant and standard dose influenza vaccines against outpatient illness during 2018-2019 and 2019-2020 calculated using a retrospective test-negative design".
A recent study by Zimmerman et al. (2023) reported non-significant higher relative vaccine effectiveness of recombinant (RIV4) over the standard-dose influenza vaccines (SDIV) against outpatient illness during the 2018-19 and 2019-20 vaccination seasons. We agree with the authors' conclusions and would like to emphasize minimal difference between RIV4 and SDIV using Number Needed to Vaccinate (NNV). The NNV analysis showed 8.9 for the RIV4 and 10 for the SDIV in the 50-64 age group. In the 65+ age group, the NNV was 10.6 for the RIV4 and 11.4 for the SDIV. This indicates a minimal difference between both vaccines and hence they both can be used in immunization programs to improve vaccine coverage.


Clinical relevance of liver membrane antibody in chronic liver disease of children.
Antibody against liver membrane (LMA) was measured using suspensions of rabbit hepatocytes and FITC-conjugated F(ab')2 fragments of affinity-purified goat anti-human IgG. The sera of 43 children with chronic liver disease were examined. Significant titers of LMA were observed for all patients with untreated HBV-negative chronic active hepatitis (CAH). Follow-up studies during immunosuppressive therapy showed that the decrease in LMA titers was delayed as compared to that of non-organ-specific antibodies, and did not correlate with clinical, biochemical, and histological parameters. The detection of LMA is useful in the diagnosis of the CAH subtype which may benefit from immunosuppressive therapy. However, it is of no assistance in the clinical management of autoimmune CAH, since it failed to predict possible relapse after withdrawal of treatment. A pathogenic role for LMA remains thus questionable.


Plasma PAFAH/PLA2G7 Genetic Variability, Cardiovascular Disease, and Clinical Trials.
PAFAH is specific for short acyl groups esterified at the sn-2 position of glycerol in phospholipids, and apart from PAF, it hydrolyzes oxidized phospholipids produced during LDL oxidation. As the majority of the plasma PAFAH activity is bound in humans to LDL, it is also called the lipoprotein-associated phospholipase A2 (Lp-PLA2), and it was associated with the proinflammatory processes in atherosclerosis. The epidemiological studies in Caucasian populations demonstrated that high PAFAH levels might be a risk factor for cardiovascular disease through generation of proinflammatory lysoPC/lysoPAF and oxidized fatty free acids and led to the development of darapladib, a reversible PAFAH inhibitor. In the preclinical study in diabetic and hypercholesterolemic pigs, darapladib decreased both plasma and in situ lesion PAFAH/Lp-PLA2 activity, reduced lesion lysoPC content, and also reduced the complex coronary lesion development by reducing the necrotic core. In the recently published double-blind trial with darapladib (STABILITY study), it was shown that darapladib did not affect the time to cardiovascular death, myocardial infarction, or stroke. Similarly, in the SOLID-TIMI 52 study, darapladib did not reduce the risk of major coronary events; for those reasons, the clinical trials with darapladib will probably definitely stop in this pathology. Finally, in the absence of a tangible effect of V279F loss-of-function mutation on the cardiovascular risk in Asiatic populations and no effect of A379V polymorphism which modifies PAFAH activity in Caucasians, combined with no effect of the anti-PAFAH/Lp-PLA2 drug darapladib in clinical trials, let us conclude that it is unlikely that PAFAH could be implicated in atherosclerosis per se. We rather believe that PAFAH/Lp-PLA2 is a biomarker of atherosclerosis.


[Comparative analysis of materials for dentino-pulp protection: varnishes, liners, ZOE cements, zinc oxyphosphate cements, zinc polycarboxylate cements, calcium hydroxide cements].
The Authors review the principal materials used for pulp and dentine protection. Them they examine the main characteristics of each materials about different clinical situations.


Impact of crossing Fayoumi and Leghorn chicken breeds on immune response against Newcastle disease virus vaccines.
This study was conducted to evaluate the immune response against Newcastle disease (ND) virus vaccines (live attenuated and inactivated) in purebred Lohman Selected Leghorn (LSL), Fayoumi, male Fayomi × female LSL (FL crossbred), male LSL × female Fayomi (LF reciprocal crossbred) chickens. One-hundred-day-old chicks of each genetic type were assigned to five equal replicates. The log geometric means of the hemagglutination inhibition (HI) antibody titers were calculated. The FL crossbred chickens had a significantly higher HI antibody titer at day 26 of age when compared with the LSL chickens (P = 0.039). The Fayoumi and FL crossbred chickens had significantly higher HI antibody titers at day 45 of age (2.35 and 2.23, respectively) when compared with the LSL chickens (P = 0.031). In the same way, the purebred Fayoumi and FL crossbred chickens had significantly higher HI antibody titers at 60 and 75 days of age (P = 0.009 and 0.041, respectively) when compared with the purebred LSL and LF crossbred chickens. The LSL chickens showed a significantly higher (P < 0.05) correlation estimate between HI titer to the ND vaccine on day 75 of age and body weight at week 12 of age. When challenged with the virulent ND virus, the hazard ratio (HR) for mortality rates in purebred LSL and LF crossbred chickens were significantly (HR = 3.52 and 2.07; P = 0.001 and 0.049, respectively) higher than the Fayoumi chickens. In conclusion, purebred Fayoumi and FL crossbred chickens showed superior antibody titers against live attenuated and inactivated ND virus vaccines. Hence, Fayoumi breed may be incorporated in the crossbreeding programs to improve the genetic resistance to ND.