Behavioral consequences of exposure to a high fat diet during the post-weaning period in rats.
We explored the impact of exposure to an obesogenic diet (High Fat-High Sucrose; HFS) during the post-weaning period on sweet preference and behaviors linked to reward and anxiety. All rats were fed chow. In addition a HFS-transient group had access to this diet for 10days from post-natal (PN) day 22 and a HFS-continuous group continued access until adult. Behavioral tests were conducted immediately after PN 32 (adolescence) or after PN 60 (adult) and included: the condition place preference (CPP) test for chocolate, sugar and saccharin preference (anhedonia), the elevated plus maze (anxiety-like behavior) and the locomotor response to quinpirole in the open field. Behavior was unaltered in adult rats in the HFS-transient group, suggesting that a short exposure to this obesogenic food does not induce long-term effects in food preferences, reward perception and value of palatable food, anxiety or locomotor activity. Nevertheless, rats that continued to have access to HFS ate less chocolate during CPP training and consumed less saccharin and sucrose when tested in adolescence, effects that were attenuated when these rats became adult. Moreover, behavioral effects linked to transient HFS exposure in adolescence were not sustained if the rats did not remain on that diet until adult. Collectively our data demonstrate that exposure to fat and sucrose in adolescence can induce immediate reward hypofunction after only 10days on the diet. Moreover, this effect is attenuated when the diet is extended until the adult period, and completely reversed when the HFS diet is removed.


Effect of timing of dialysis on mortality in critically ill, septic patients with acute renal failure.
Acute renal failure with concomitant sepsis in the intensive care unit is associated with significant mortality. The purpose of this study was to determine if the timing of initiation of renal replacement therapy (RRT) in septic patients had an effect on the 28-day mortality. Retrospective data on medical intensive care unit patients with sepsis and acute renal failure requiring RRT were included. Renal replacement therapy started with a blood urea nitrogen (BUN) of <100 mg/dL was defined as "early" initiation, and initiation with a BUN >or=100 mg/dL was defined as "late." Multivariate logistic regression analysis with the primary outcome of death at 14, 28, and 365 days following the initiation of RRT was performed. One hundred thirty patients were studied. The early dialysis (mean BUN 66 mg/dL) group had 85 patients; the late group (mean BUN 137 mg/dL) had 62 patients. The mean acute physiology and chronic health evaluation II score was 24.5 in both groups. The overall 14, 28, and 365-day survival rates were 58.1%, 41.9%, and 23.6%. Survival rates for the early group were 67%, 47.7%, and 30.7% at 14, 28, and 365 days. Survival rates for the late group were 46.7%, 31.7%, and 13.3% at 14, 28, and 365 days. Upon logistic regression analysis, initiating dialysis with a BUN >100 mg/dL predicted death at 14 days (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.7-7.6, P=0.001), 28 days (OR 2.6, 95% CI 1.2-5.7, P=0.01), and 365 days (OR 3.5, 95% CI 1.2-10, P=0.02). Septic patients who started dialysis with a BUN <100 mg/dL had improved mortality rates up to 1 year after initiation of dialysis in this single-center, retrospective analysis.


Energy expenditure and consumption of mature, pregnant and lactating women.
Activity patterns, energy expenditure, and energy and protein consumption of mature women were determined during preganncy and lactation. Homemakers of average economic status from a mixed population were not significantly more active than teenage women, but the range of activities was greater. Average energy output for the latter half of gestation was 2,200 to 2,300 kcal per day; per unit of body weight, the mean was 32.5 +/- 4 kcal per kilogram for the twenty-week period. A small decline of 6 per cent in energy expenditure was noted near term. Allowing for deposition of fetal and material tissue, the average metabolizable energy need for this group was about 35 to 36 kcal per kilogram for the latter half of pregnancy. These data show that a pregnant woman of reference body weight (68 kg.) may vary in energy output by 800 to 900 kcal per day, depending on occupation. Homemakers with small children and especially those who work outside the home constitute a high energy work category. Thus, the need for considering work pace and work load, as well as body mass, in estimating the energy requirement during pregnancy was confirmed. Average daily energy intake reported was 1,955 kcal or 28.5 kcal per kilogram for the latter half of gestation. A mean protein intake of 1.17 gm. per kilogram per day represented 17 per cent of gross energy consumed. It is questionable whether the energy level consumed by these women was sufficient to maintain positive nitrogen balance on the days recorded. Lactating homemakers expended an average of 30 kcal per kilogram per day, exclusive of milk production. Energy intake was 30 kcal per kilogram, and was equal to 74 per cent of need when adjusted for milk production. Non-lactating women expended 34 kcal per kilogram per day, 13 per cent above the values for lactating women. Average energy intake of non-lactating women was 19 kcal per kilogram, with protein intake representing 19 per cent of energy consumed for both groups.


LTA4H regulates cell cycle and skin carcinogenesis.
Leukotriene A4 hydrolase (LTA4H), a bifunctional zinc metallo-enzyme, is reportedly overexpressed in several human cancers. Our group has focused on LTA4H as a potential target for cancer prevention and/or therapy. In the present study, we report that LTA4H is a key regulator of cell cycle at the G0/G1 phase acting by negatively regulating p27 expression in skin cancer. We found that LTA4H is overexpressed in human skin cancer tissue. Knocking out LTA4H significantly reduced skin cancer development in the 7,12-dimethylbenz(a)anthracene (DMBA)-initiated/12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted two-stage skin cancer mouse model. LTA4H depletion dramatically decreased anchorage-dependent and -independent skin cancer cell growth by inducing cell cycle arrest at the G0/G1 phase. Moreover, our findings showed that depletion of LTA4H enhanced p27 protein stability, which was associated with decreased phosphorylation of CDK2 at Thr160 and inhibition of the CDK2/cyclin E complex, resulting in down-regulated p27 ubiquitination. These findings indicate that LTA4H is critical for skin carcinogenesis and is an important mediator of cell cycle and the data begin to clarify the mechanisms of LTA4H's role in cancer development.


Coupling effects in volume selective 1H spectroscopy of major brain metabolites.
The effect of PRESS and STEAM sequences on the spectra of coupled substances are discussed using the examples of weakly coupled AX and A2X systems. Maximum differences compared to uncoupled spins occur if the RF pulses are applied to antiphase magnetization. In this case, the spin echo of the PRESS experiment shows a modified dependence on the refocusing flip angle, which may lead to an attenuation of the acquired signal. In STEAM spectroscopy the evolution within the middle interval tm is dominated by zero quantum coherences and longitudinal polarization, whose maximum efficiencies are 25 and 12.5%, respectively. Zero quantum coherences may lead to strong modulations when the tm value is varied. The effects on the spectra of important coupled metabolites of the human brain such as glutamate, GABA, inositol, and particularly lactate, are demonstrated. The observed modulations seem to make the quantification of the spectra rather difficult at echo times above 50 ms.


Zinc Modulates Glutamine Metabolism in T Cells.
Zinc and glutamine are well known to be essential for the function and polarization of immune cells. TH 17 cells are more frequently induced during zinc deficiency and cover their energy requirement mainly through glutaminolysis. A dysregulation of TH 17 cells can contribute to the development of autoimmune diseases. Both inhibition of glutaminolysis and zinc supplementation suppress experimental autoimmune encephalomyelitis in mice. Therefore, the aim of this study is to investigate whether zinc modulates glutaminolysis in T cells. CD3/CD28 stimulation and mixed lymphocytes culture are used as in vitro models for T cell activation. Then, the glutaminolysis is investigated on mRNA, protein, and functional level. Zinc deficiency and glutaminase (GLS) inhibition decrease immune responses in vitro. Furthermore, extracellular zinc and glutamine levels both modulate glutaminolysis by changing the expression of glutamine transporters and key enzymes. Intriguingly, zinc directly interferes with the activity of GLS both in a cell free system and in the cytosol. Besides T cell subset differentiation, zinc also impacts on the cellular metabolism by inhibiting glutaminolysis. This suggests that zinc deficiency can contribute to the development of autoimmune diseases whereas zinc supplementation can support their therapy.


Aging Mother-Adult Daughter Differentiation, Psychological Well-Being, and Parental Status.
Despite the understanding that differentiation is a lifelong process crucial for psychological adaptation, there is limited knowledge regarding how parent-child differentiation in adulthood is associated with the psychological well-being of both parents and adult children. Furthermore, empirical research has yielded inconclusive results regarding whether the parental status of adult children influences the parent-child relationship. Consequently, the current study focuses on the moderating effect of adult daughters' parental status on the association between aging mother-adult daughter differentiation and psychological well-being. The study utilized data from 167 pairs of Korean aging mothers and adult daughters to examine two main aspects: (1) the relationship between aging mother-adult daughter differentiation and psychological well-being; and (2) the moderating role of adult daughters' parental status on the relationship between aging mother-adult daughter differentiation and psychological well-being. The findings revealed that both the differentiation of adult daughters and mothers was positively associated with their respective psychological well-being. However, no significant cross-interactional effects of aging mother-adult daughter differentiation on psychological well-being were observed. Notably, there was a positive moderating effect of the adult daughter's parental status on the association between aging mother-adult daughter differentiation and psychological well-being for aging mothers.


The early development of joint attention in infants with autistic disorder using home video observations and parental interview.
The aim in the current study was to investigate the early development of joint attention, eye contact and affect during the first 2 years of life, by using retrospective parental interviews and analyses of home videos of infants who were later diagnosed with Autistic Disorder (AD). The 36 children with AD and the 27 matched control children were all aged between 3 and 5 years at recruitment. Reported anomalies in gaze and affect emerged in the children with AD as early as the first 6 months of life, generally becoming more severe just prior to the second birthday. Video data confirmed these anomalies from as early as the first year. Joint attention impairments were found throughout the second year of life. The results suggest that early dyadic behaviours-eye contact and affect-may play a role in the joint attention impairment in AD.


Pharmacological and nutritional therapy of children and adults with chronic intestinal pseudo-obstruction.
Chronic intestinal pseudoobstruction (CIPO) is a rare, heterogenous, and severe form of gastrointestinal dysmotility. Pertinent literature on pediatric and adult CIPO management has been assessed via PubMed, Scopus, and EMBASE from inception to June 2022. Prokinetics, aimed at restoring intestinal propulsion (e.g. orthopramides and substituted benzamides, acetyl cholinesterase inhibitors, serotonergic agents, and others), have been poorly tested and the available data showed only partial efficacy. Moreover, some prokinetic agents (e.g. orthopramides and substituted benzamides) can cause major side effects. CIPO-related small intestinal bacterial overgrowth requires treatment preferably via poorly absorbable antibiotics to avoid bacterial resistance. Apart from opioids, which worsen gut motility, analgesics should be considered to manage visceral pain, which might dominate the clinical manifestations. Nutritional support, via modified oral feeding, enteral, or parenteral nutrition, is key to halting CIPO-related malnutrition. There have been significant roadblocks preventing the development of CIPO treatment. Nonetheless, the considerable advancement in neurogastroenterology and pharmacological agents cast hopes to test the actual efficacy of new prokinetics via well-designed clinical trials. Adequate dietary strategies and supplementation remain of crucial importance. Taken together, novel pharmacological and nutritional options are expected to provide adequate treatments forthese patients.


Clinical trade-offs in cross-linked ultrahigh-molecular-weight polyethylene used in total joint arthroplasty.
Highly cross-linked formulations of ultrahigh-molecular-weight polyethylene (XLPE) offer exceptional wear resistance for total joint arthroplasty but are offset with a reduction in postyield and fatigue fracture properties in comparison to conventional ultrahigh-molecular-weight polyethylene (UHMWPE). Oxidation resistance is also an important property for the longevity of total joint replacements (TJRs) as formulations of UHMWPE or XLPE utilizing radiation methods are susceptible to free radical generation and subsequent embrittlement. The balance of oxidation, wear, and fracture properties is an enduring concern for orthopedic polymers used as the bearing surface in total joint arthroplasty. Optimization of material properties is further challenged in designs that make use of locking mechanisms, notches, or other stress concentrations that can render the polymer susceptible to fracture due to elevated local stresses. Clinical complications involving impingements, dislocations, or other biomechanical overloads can exacerbate stresses and negate benefits of improved wear resistance provided by XLPE. This work examines trade-offs that factor into the use of XLPE in TJR implants.


The freshwater cyanobacterium Anabaena doliolum transformed with ApGSMT-DMT exhibited enhanced salt tolerance and protection to nitrogenase activity, but became halophilic.
Glycine betaine (GB) is an important osmolyte synthesized in response to different abiotic stresses, including salinity. The two known pathways of GB synthesis involve: 1) two step oxidation of choline (choline → betaine aldehyde → GB), generally found in plants, microbes and animals; and 2) three step methylation of glycine (glycine → sarcosine → dimethylglycine → GB), mainly found in halophilic archaea, sulphur bacteria and the cyanobacterium Aphanothece (Ap.) halophytica. Here, we transformed a salt-sensitive freshwater diazotrophic filamentous cyanobacterium Anabaena (An.) doliolum with N-methyltransferase genes (ApGSMT-DMT) from Ap. halophytica using the triparental conjugation method. The transformed An. doliolum synthesized and accumulated GB in cells, and showed increased salt tolerance and protection to nitrogenase activity. The salt responsiveness of the transformant was also apparent as GB synthesis increased with increasing concentrations of NaCl in the nutrient solution, and maximal [12.92 µmol (g dry weight)(-1)] in cells growing at 0.5 M NaCl. Therefore, the transformed cyanobacterium has changed its behaviour from preferring freshwater to halophily. This study may have important biotechnological implications for the development of stress tolerant nitrogen-fixing cyanobacteria as biofertilizers for sustainable agriculture.


Spatio-temporal dynamics and aetiology of proliferative leg skin lesions in wild British finches.
Proliferative leg skin lesions have been described in wild finches in Europe although there have been no large-scale studies of their aetiology or epizootiology to date. Firstly, disease surveillance, utilising public reporting of observations of live wild finches was conducted in Great Britain (GB) and showed proliferative leg skin lesions in chaffinches (Fringilla coelebs) to be widespread. Seasonal variation was observed, with a peak during the winter months. Secondly, pathological investigations were performed on a sample of 39 chaffinches, four bullfinches (Pyrrhula pyrrhula), one greenfinch (Chloris chloris) and one goldfinch (Carduelis carduelis) with proliferative leg skin lesions and detected Cnemidocoptes sp. mites in 91% (41/45) of affected finches and from all species examined. Fringilla coelebs papillomavirus (FcPV1) PCR was positive in 74% (23/31) of birds tested: a 394 base pair sequence was derived from 20 of these birds, from all examined species, with 100% identity to reference genomes. Both mites and FcPV1 DNA were detected in 71% (20/28) of birds tested for both pathogens. Histopathological examination of lesions did not discriminate the relative importance of mite or FcPV1 infection as their cause. Development of techniques to localise FcPV1 within lesions is required to elucidate the pathological significance of FcPV1 DNA detection.


In vivo mutagenicity of conazole fungicides correlates with tumorigenicity.
Triadimefon, propiconazole and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. All three conazoles are generally inactive in short-term genotoxicity tests. We studied the in vivo mutagenicity of these three conazoles using the Big Blue mouse assay system. Groups of mice were fed either control diet or diet containing 1800 p.p.m. triadimefon, 2500 p.p.m. propiconazole or 2000 p.p.m. myclobutanil. After 4 days of feeding, mice were immediately euthanized, livers were removed, DNA isolated and lacI genes recovered into infectious bacteriophage lambda particles by in vitro packaging. Bacteriophage with mutations in the lacI gene was detected by infecting into Escherichia coli, and mutant frequencies were determined using a colorimetric plaque assay. Propiconazole induced a 1.97-fold increase in mutant frequency compared to concurrent controls (P = 0.018) and triadimefon induced a 1.94-fold increase compared to concurrent controls (P = 0.009). Myclobutanil did not induce any change in mutant frequency (P = 0.548). These results provide the first evidence that the hepatotumorigenic conazoles are capable of inducing mutations in liver in vivo while the non-tumorigen myclobutanil is not, suggesting that mutagenicity may represent a key event in conazoles tumorigenic mode of action.


Benign pheochromocytoma presented 6 years after kidney transplantation.
Hypertension is very common in kidney transplant patients; however, severe and resistant cases should raise suspicion of secondary causes. Pheochromocytomas are rare but serious tumors because of their lethal hypertensive and possible malignant nature. The diagnosis is occasionally elusive, but prompt diagnosis and localization is essential for definitive surgical management. We report a case of a patient with benign pheochromocytoma presenting largely asymptomatically, but with severe resistant hypertension, 6 years after kidney transplantation. To the best of our knowledge, this is the first case report of this type of tumor after kidney transplantation.


The Effects of One-Stage Full-Mouth Disinfection and Qua-drant-Wise Scaling and Root Planing on Serum Levels of IL-17 and IL-1β and Clinical Parameters (A randomized Controlled Trial Study).
One-stage full-mouth disinfection technique (FMD) has been introduced to avoid cross-contamination between the treated and untreated regions between treatment sessions. Considering the role of inflammatory mediators in periodontitis, the aim of the present study was to compare the effects of FMD with the quadrant-wise scaling and root planing (Q-SRP) on serum levels of IL-17 and IL-1β in patients with moderate-to-severe chronic periodontitis. Twenty patients with chronic periodontitis were selected randomly and based on inclusion criteria in each group. In order to evaluate the periodontal status, the clinical parameters of bleeding on probing (BOP), clinical attachment level (CAL), probing depth (PD) and modified gingival index (MGI) were measured and recorded before treatment and at 2- and 4-month intervals after treatment. Immunologic parameters of the study such as IL-17 and IL-1β serum levels were determined by special laboratory kits at the same intervals. Data were analyzed by SPSS 15 statistical software. Statistical significance was defined at p<0.05. The results showed a decrease in the means of IL-17 and IL-1β serum levels in both treatment modalities, with no statistically significant differences between the two study groups at the two time intervals (p>0.05). In the evaluation of periodontal parameters, all parameters exhibited clinical improvements in both groups, with no statistically significant differences between the two study groups (p>0.05). Based on the results of the present study it was concluded that both FMD and Q-SRP techniques result in improvements in periodontal indexes and decreases in the serum levels of IL-17 and IL-1β inflammatory mediators.


Genome-wide association study provides strong evidence of genes affecting the reproductive performance of Nellore beef cows.
Reproductive traits are economically important for beef cattle production; however, these traits are still a bottleneck in indicine cattle since these animals typically reach puberty at older ages when compared to taurine breeds. In addition, reproductive traits are complex phenotypes, i.e., they are controlled by both the environment and many small-effect genes involved in different pathways. In this study, we conducted genome-wide association study (GWAS) and functional analyses to identify important genes and pathways associated with heifer rebreeding (HR) and with the number of calvings at 53 months of age (NC53) in Nellore cows. A total of 142,878 and 244,311 phenotypes for HR and NC53, respectively, and 2,925 animals genotyped with the Illumina Bovine HD panel (Illumina®, San Diego, CA, USA) were used in GWAS applying the weighted single-step GBLUP (WssGBLUP) method. Several genes associated with reproductive events were detected in the 20 most important 1Mb windows for both traits. Significant pathways for HR and NC53 were associated with lipid metabolism and immune processes, respectively. MHC class II genes, detected on chromosome 23 (window 25-26Mb) for NC53, were significantly associated with pregnancy success of Nellore cows. These genes have been proved previously to be associated with reproductive traits such as mate choice in other breeds and species. Our results suggest that genes associated with the reproductive traits HR and NC53 may be involved in embryo development in mammalian species. Furthermore, some genes associated with mate choice may affect pregnancy success in Nellore cattle.


The pre-surgical factors that determine the decision to proceed to resection in children diagnosed with high-risk neuroblastoma in a resource limited setting.
Surgical control has prognostic value in neuroblastoma (NB). Advanced NB is common at diagnosis in South Africa. We investigated the pre-surgery factors that influenced decisions to perform surgical resections. We included 204 patients with high-risk NB from a national retrospective study, who completed induction chemotherapy between 2000 and 2016.The median age was 32.4 months (IQR 15.1 - 53.5 months). Primary tumor resection was achieved in 76.9% of patients between 0-18 months of age, 51.8% between 18-60 months and 51.7% older than 60 months (p < 0.001). Only 43.2% of patients with distant metastatic disease had surgery done (p < 0.001). LDH was >750 U/L in 46.8% and ferritin >120 g/dL in 53.1% of those who had surgery (p = 0.005). The majority (80.4%), who had achieved post-induction metastatic complete remission (mCR), were operated, while 28.7% without mCR had surgery (p < 0.001). The long-term overall survival in patients with mCR and primary tumor resection was 36.5% compared to those with mCR without primary tumor resection (25.4%) and without mCR (≤3.0%)(p < 0.001). Age (p < 0.001), stage (p < 0.001), mCR (p < 0.001) and treatment setting (p < 0.001) were of prognostic significance. The tumor site and MYCN-amplification did not significantly predict resection rates. Post-induction mCR and stage were associated with surgical resection and five-year OS (p < 0.001) on multivariate analysis.Patients with high-risk NB who achieved mCR and had primary tumor resections are curable in limited resourced settings. Stage and post-induction mCR were significant variables that led to surgery. These variables should be included as indications in the management of metastatic NB in resource limited settings.


The unappreciated roles of the cholecystokinin receptor CCK(1) in brain functioning.
The CCK(1) receptor is a G-protein-coupled receptor activated by the sulfated forms of cholecystokinin (CCK), a gastrin-like peptide released in the gastrointestinal tract and mammal brain. A substantial body of research supports the hypothesis that CCK(1)r stimulates gallbladder contraction and pancreatic secretion in the gut, as well as satiety in brain. However, this receptor may also fulfill relevant roles in behavior, thanks to its widespread distribution in the brain. The strategic location of CCK(1)r in mesolimbic structures and specific hypothalamic and brainstem nuclei lead to complex interactions with neurotransmitters like dopamine, serotonin, and glutamate, as well as hypothalamic hormones and neuropeptides. The activity of CCK(1)r maintains adequate levels of dopamine and regulates the activity of serotonin neurons of raphe nuclei, which makes CCK(1)r an interesting therapeutic target for the development of adjuvant treatments for schizophrenia, drug addiction, and mood disorders. Unexplored functions of CCK(1)r, like the transmission of interoceptive sensitivity in addition to the regulation of hypothalamic hormones and neurotransmitters affecting emotional states, well-being, and attachment behaviors, may open exciting roads of research. The absence of specific ligands for the CCK(1) receptor has complicated the study of its distribution in brain so that research about its impact on behavior has been published sporadically over the last 30 years. The present review reunites all this body of evidence in a comprehensive way to summarize our knowledge about the actual role of CCK in the neurobiology of mental illness.


Surgical management of double-head pterygium by using a novel technique: conjunctival rotational autograft combined with conjunctival autograft.
To describe a novel technique for the surgical management of double-head pterygium and to evaluate its safety and efficacy. A prospective noncomparative interventional case series was conducted. Patients with primary double-head pterygium underwent pterygium excision, followed by conjunctival rotational autograft (CRA) combined with conjunctival autograft (CA). CRA was harvested from the larger pterygium and placed over the bare scleral defect of the smaller pterygium with 180-degree rotation. The bare scleral defect of the larger pterygium was covered with CA harvested from the superior bulbar conjunctiva. Patients were followed up for 1 year, and the outcomes and recurrence rates were noted. Twenty patients were recruited into the study, of which 7 (35%) were men and 13 (65%) were women. The mean age was 63.8 years. No intraoperative complication was encountered. Postoperatively, there was significant improvement in best-corrected visual acuity (P = 0.005) and reduction in magnitude of astigmatism (P = 0.016). At 1 year after operation, there were 7 cases of recurrence (35%), but 4 were 1 mm. The main postoperative complication was persistent CRA injection in 9 cases. CRA combined with CA is a safe alternative in the management of double-head pterygium. Further modifications of the surgical techniques are warranted to decrease prolonged hyperemia of the CRA.


Applications of a health planning model in Morocco.
It is argued in this paper that public health planning should be guided by the principle of output maximization. The objective of the health sector should be specified, and measurable forms of output should be derived from these statements of purpose. Knowledge of the contributions which given combinations of inputs make toward output thus defined allow, in principle, calculation of the particular deployment of the avilable inputs which will maximize output. There is a discussion of the objectives or forms of output in a public health system, both humanitarian and economic. A verbal model of such a system for an underdeveloped country is constructed which identifies the relationships which must be known if spending decisions are to suceed in maximizing output. An attempt is then made, in the context of the Moroccan public health system, to show that the model is not merely a theoretical exercise, but is potentially useful as a planning instrument. The respective contributions of general hospitals and of mass vaccination programs toward the objective of reducing mortality are estimated. On the whole, the preventive activities (the mass vaccinations) are found to be a much a cheaper way of saving lives than are the curative activities (the general hospitals).


The effect of radiofrequency catheter ablation of frequent premature ventricular complexes and arrhythmia burden on left ventricular function.
Frequent premature ventricular complexes (PVC) are related to reversible tachycardia-induced cardiomyopathy. However, the role of arrhythmia burden on the outcome of the catheter ablation has not been fully recognised. The aim of this study was to assess the effect of catheter ablation and PVC burden in patients with and without structural heart disease (SHD) on left ventricular ejection fraction (LVEF). Transthoracic echocardiography was done before and six months after radiofrequency catheter ablation in 109 consecutive patients (61 men, age 55 ± 17 years) with frequent PVCs. Sixty-five (59.6%) patients had underlying SHD. The catheter ablation procedure was successful in 93 (85.3%) patients. Baseline PVC burden was higher in patients with SHD (22,267 ± 12,934) compared to those without concomitant SHD (15,546 ± 7888), p = 0.005. Nevertheless, patients with LVEF ≤ 50% at baseline presented greater LVEF recovery (from 44% to 56%) than those with LVEF > 50% at baseline after catheter ablation. In both groups, the LVEF improved (p < 0.001); however, no difference was observed be-tween patients with SHD (5.7% ± 1.37%) and without (4.6% ± 0.96%) SHD; p = 0.89. PVC burden was higher in patients with (24,350 ± 2776 PVC/day) compared to those without (17,588 ± 1970 PVC/day) improvement of LVEF. In multivariate regression analysis PVC burden > 20,000/day (but not age, p = 0.95; gender, p = 0.89; presence of SHD, p = 0.53; QRS complex width of the treated PVC, p = 0.21, LVEF before ablation, p = 0.19; and site of origin, p = 47) predicted improvement in LVEF after successful catheter ablation (odds ratio: 3.53; 95% confidence interval: 1.15-10.75; p = 0.023). Catheter ablation of frequent PVCs improves left ventricular function in multivariate analysis predicted improvement of LVEF within six months after the successful catheter ablation procedure in patients with PVC burden exceeding 20,000/24 h.


[Selenium: physiologic role and value in human pathology].
Selenium (Se) is a metalloid with chemical properties closed to those of sulfur, but they can not substitute for one another in vivo. Se body content reflected soil Se content (13 to 20 mg in North Americans, 3 to 6 in New Zealand residents). The daily intake recommended is 50 to 200 micrograms. In the diet Se occurs in mineral or organic forms, the bioavailability of these latter is better. Se as selenocysteine is incorporated in specific proteins such as glutathione peroxidase (GSH-Px). Se is metabolized in H2Se by reductive pathways. H2Se is methylated and methylated compounds are excreted in the urines. The Se urinary excretion represents the principal known process of Se regulation. Se bound to GSH-Px participates to free radical destruction and cellular membrane protection. Its role is complementary of vitamin E effect. Se also seems indispensable to appropriate immune response. It can chelate various metals allowing their detoxication. Se metabolism can be studied by Se assay in serum, whole blood, urine (reference values must be performed for each studied population) and by GSH-Px activity determination in erythrocytes or platelets. Vitamin E assay completes estimation of the antioxidative status of organism. Few Se intoxications have been recognized but Se deficiencies often happen. They can lead to a cardiomyopathy (Keshan disease), increase the risk of cardiovascular diseases or cancer. Se deficiencies are found in chronic renal failure, malnutrition malabsorption, long term parenteral nutrition. At the present time it is not known how Se deficiency interfers with chronic infections which often go with these diseases. A better knowledge of Se requirements and Se role could allow an appropriate supplementation in various diseases.


Hodgkin's disease after treatment for Burkitt's lymphoma: case report.
Hodgkin's disease and non-Hodgkin's lymphomas are interrelated disorders which have been reported to occur either simultaneously or sequentially in the same patient. We report here the development of nodular sclerosing type Hodgkin's disease in a patient two decades after successful treatment for Burkitt's lymphoma with cyclophosphomide and abdominal resection (AR). While the onset of symptoms after treatment for Burkitt's lymphoma was seven years definitive diagnosis of Hodgkin's disease was only made 22 years after the initial diagnosis of Burkitt's lymphoma. The recurrent and solitary nature ofthe lymphadenopathy and the fact that it was initially reported as reactive hyperplasia is typical of nodular lymphocyte predominant Hodgkin's disease. We believe that there was a transitory period of the malignancy as nodular lymphocyte predominant Hodgkin's disease.


Microvascular adaptation in the cerebral cortex of adult spontaneously hypertensive rats.
The purpose of this study was to determine the microvascular characteristics that cause cerebral cortical blood flow autoregulation to shift to a higher range of arterial pressures during established hypertension in spontaneously hypertensive rats (SHR). An open-skull technique with constant suffusion of artificial cerebrospinal fluid (PO2 = 40-45 mm Hg, PCO2 = 40-45 mm Hg, pH = 7.35-7.45) was used to view the parietal cortex of 18- to 21-week-old SHR and Wistar Kyoto (WKY) normotensive control rats. The resting inner diameters of first (1A)-, second (2A)-, and fourth (4a)-order arterioles were significantly (p less than 0.05) smaller, and the wall thickness/lumen diameter ratios were significantly (p less than 0.05) larger in SHR compared to WKY. Only 1A and 4A has significantly (p less than 0.05) increased vessel wall cross-sectional area in SHR. At the resting mean arterial pressures of WKY and SHR, the passive (10(-4) M adenosine, topical) diameters of comparable types of arterioles were not significantly different (p greater than 0.05). At reduced arterial pressures, however, the arterioles in SHR had smaller maximum diameters than in WKY. Cortical blood flow in WKY and SHR was constant at arterial pressures from 70-150 mm Hg and 100-200 mm Hg, respectively. Resting arteriolar pressures in 1A, 2A, and 3A of SHR were substantially and significantly (p less than 0.05) elevated, although pressures in the smallest arterioles and venules of WKY and SHR were similar. Therefore, it is possible that cerebral capillary pressure is only slightly elevated, if at all, in SHR as a result of the vasoconstriction. The number of arterioles per unit area of brain surface at rest was equal in WKY and SHR. In addition, the number of vessels was equal in WKY and SHR during maximal dilation, and neither type of rat demonstrated an opening of previously closed vessels upon maximum dilation. Therefore, the cerebral arteriolar constriction in SHR, which was probably potentiated by vessel wall hypertrophy of the largest and smallest arterioles, was the major contributor to an upward shift in the autoregulatory range, the protection of exchange vasculature pressures, and the increase in vascular resistance.


Frequency and Characteristics of Paraclinoid Aneurysm in Ruptured Cerebral Aneurysms.
This study aimed to determine the frequency of paraclinoid aneurysms among ruptured cerebral aneurysms and compare paraclinoid aneurysms with other aneurysms to clarify the characteristics of ruptured paraclinoid aneurysms. This study included 970 ruptured cerebral aneurysms treated at our hospital between 2003 and 2020. There were 15 cases (1.3%) of paraclinoid aneurysms with maximum diameters of 5 mm - 22 mm (11.6 ± 5.4 mm [mean ± standard deviation]). Treatment consisted of clipping in 4 patients and endovascular treatment in 11. Factors significantly different in multivariate analysis for paraclinoid aneurysms compared with those for other aneurysms were a history of hypertension (p = 0.021, OR: 1.2- 9.8) and aneurysm ≥10 mm (p < 0.001, OR: 7.5 - 390.3). The sites of paraclinoid aneurysm were ophthalmic artery type in nine patients, anterior wall type in five, medial wall type in one, and ventral wall type in zero. The medial wall type (22 mm) was significantly larger than the ophthalmic artery type (7.2 ± 2.0 mm, mean ± standard deviation) (p = 0.003), and the anterior wall type (12.2 ± 4.8 mm) was significantly larger than the ophthalmic artery type (p = 0.024). This study showed a low frequency of paraclinoid aneurysms among ruptured cerebral aneurysms. Most were upward-facing with relatively large aneurysms, and no aneurysms were smaller than 5 mm. With recent advances in endovascular treatment devices, paraclinoid aneurysms are easily treatable. However, the treatment indication of each paraclinoid aneurysm should be carefully considered.


Uniquely altered transcripts are associated with immune preservation in HIV infection.
The mechanisms underlying host HIV control hold much promise in the search for a functional HIV cure. We investigated the host genomic signatures in elite controllers or rapid progressors following recent infection and the correlates of immune reconstitution during combination antiretroviral therapy. We characterized the HIV-specific longitudinal host transcriptional response of peripheral blood mononuclear cells from elite controllers, rapid progressors, immune responders and non-responders using a RT-qPCR array in a cohort of recently HIV-infected Brazilian individuals. The elite controllers expressed unique transcripts early in infection that were closely associated with specialized cross-presentation between XCR1+ DCs and antigen-specific CD8+ T cells (XCL1). The natural suppression of HIV was also associated with the highly functional co-expression of cytokines and chemokines (CCL2, TNF and IL-10) concomitant with the maintenance of important anti-inflammatory and anticoagulant properties (Antithrombin III). Immune responders exhibited exclusively upregulated mRNAs possibly related to stem cell mobilization before combination antiretroviral therapy (neutrophil elastase). Our longitudinal approach to gene expression permitted us to discover previously unrecognized determinants that contribute to natural or antiretroviral-mediated HIV-1 immune control.


Coactivators enable glucocorticoid receptor recruitment to fine-tune estrogen receptor transcriptional responses.
Nuclear receptors (NRs) are central regulators of pathophysiological processes; however, how their responses intertwine is still not fully understood. The aim of this study was to determine whether and how steroid NRs can influence each other's activity under co-agonist treatment. We used a unique system consisting of a multicopy integration of an estrogen receptor responsive unit that allows direct visualization and quantification of estrogen receptor alpha (ERα) DNA binding, co-regulator recruitment and transcriptional readout. We find that ERα DNA loading is required for other type I nuclear receptors to be co-recruited after dual agonist treatment. We focused on ERα/glucocorticoid receptor interplay and demonstrated that it requires steroid receptor coactivators (SRC-2, SRC-3) and the mediator component MED14. We then validated this cooperative interplay on endogenous target genes in breast cancer cells. Taken together, this work highlights another layer of mechanistic complexity through which NRs cross-talk with each other on chromatin under multiple hormonal stimuli.


Influence of illuminating beyond the object support on Zernike-type phase contrast filtering.
A general analysis of the image fill-factor influence on Zemike-type phase contrast filtering is presented. We define image fill factor as the ratio of the object support area over the illuminating area. We first consider binary-phase objects and then generalize to arbitrarily quantized and continuous-phase objects. Numerical simulations are presented for binary- and quadratic-phase objects, where the contrast of the output image is evaluated as a function of the image fill factor, image phase variations, and filter phase. The results obtained show that the image fill factor can significantly modify the contrast and irradiance of the contrasted image.


Use of imaging guides in preimplant tomography.
The objective of this study was to quantify the variation in use and type of imaging guides used by community-based specialists and general practitioners during dental implant treatment planning phases. The specific aim of this study was to test the hypothesis that specialists are more likely to use some form of cross-sectional imaging in conjunction with imaging guides during the preoperative assessment of dental implant procedures. Records from 630 patients with implants (1640 implants) referred for cross-sectional tomography were reviewed. Imaging guide type and implant sites were noted. The distribution of referring dentists by specialty was as follows: general practitioners (42.2%), periodontists (35.1%), oral and maxillofacial surgeons (13.3%), and prosthodontists (7%). Of patients referred for tomograms, 52% were referred without a surgical guide. Specialists ordered tomograms in conjunction with imaging guides more often than did general practitioners. Prosthodontists and periodontists preferred to use more restrictive guides than did general practitioners or oral and maxillofacial surgeons.


Recurrent ischemic colitis in a patient with malignant rheumatoid arthritis (MRA).
Abstract A 63-year-old male with a 5-year history of malignant rheumatoid arthritis (MRA) developed recurrent massive melena and abdominal pain. Methylprednisolone pulse therapy and high doses of oral prednisolone markedly improved the clinical symptoms and normalized immunological disorders. However, he died of disseminated intra-vascular coagulation secondary to pneumonia caused by methicillin-resistant Staphylococcus aureus. Although a high dose of glucocorticoid therapy is effective for ischemic colitis complicated with MRA, intensive care to avoid any opportunistic infection is required.


The effects of self-efficacy statements in humorous anti-alcohol abuse messages targeting college students: who is in charge?
This study examined the effect of self-efficacy statements in humorous anti-alcohol abuse television advertisements on college students. A posttest only group design experiment was conducted with 124 college students. It was found that highly rebellious individuals who watched ads with a self-efficacy statement (i.e., "You Are in Control of the Situation") indicated lower alcohol expectancies, higher risk perceptions, and higher intentions to change their drinking behaviors than those in the non-self-efficacy condition. The findings suggest that health promotional messages should be tailored to rebellious college students, particularly those who are at risk, in a manner that not only gains their attention but also minimizes possible defensive reactions to the given messages. Humorous messages with self-efficacy statements could offer ways to communicate with rebellious college students regarding their drinking problems.


Cardioplegia delivery by transcutaneous pigtail catheter in minimally invasive mitral valve operations.
For cardioplegia delivery and removing air from the aorta in minimally invasive mitral valve operations, we would like to propose a cost-effective pigtail method. The 8F pigtail punctures the aorta, delivers cardioplegia, and stays in place for removing air from the aorta. We then slide its tip out of the aorta as an accessory drain. With more than 100 successes, we are using it in every case and would like to share it with peer surgeons.


Clot structure modification by fondaparinux and consequence on fibrinolysis: a new mechanism of antithrombotic activity.
Fondaparinux is a synthetic pentasaccharide consisting of the minimal sequence of heparin which interacts with antithrombin (AT). It represents a new class of selective factor Xa inhibitors without any antithrombin activity. It has been shown to exhibit potent antithrombotic properties in clinical studies. However, the mechanism of its antithrombotic action has not yet been fully established. In the present study it was shown that fondaparinux, used at pharmacological concentration (500 ng/ml), rendered the clot more susceptible to fibrinolysis induced by t-PA: plasma fibrin clots formed in the presence of fondaparinux and perfused with t-PA were degraded at a faster rate than those formed in the absence of fondaparinux. This fibrinolytic activity of fondaparinux is mainly due to a modification of clot structure characterized by a loose fibrin conformation with less branched fibers and the presence of large pores in comparison to control clots which present a tighter conformation. The difference in fibrin structure was responsible for an increase in clot porosity leading to a better availability of t-PA to the fibrin network. It is related to the decrease in thrombin generation, in an AT-dependent pathway. It was also demonstrated that in the presence of exogenous thrombomodulin, the inhibition of TAFI activation by fondaparinux could contribute, to a lesser extent, to the increased thrombus lysis. The increase in t-PA induced thrombus lysis could contribute to the antithrombotic activity of fondaparinux.


Mutant of Escherichia coli with thermosensitive protein in the process of cellular division.
A new thermosensitive mutant of Escherichia coli deficient in cell division was isolated by means of membrane filtration after nitrosoguanidine mutagenesis. The mutant cells grow normally at 30 C but stop dividing immediately after shift to 42 C, resulting in multinucleated filaments lacking septa. The number of colony-forming units does not decrease for at least 6 hr at 42 C. The maximum length of the filaments is 10 to 16 times that of normal cells. Addition of a high concentration of NaCl fails to stimulate cell division at 42 C. The filaments formed at 42 C divide abruptly 30 min after shift to 30 C, and synchronous increase of cell number is shown for 3 hr. The macromolecular synthesis of protein and nucleic acids at 42 C is normal on the whole. The cell division shown after the shift from 42 to 30 C is observed in the absence of thymine, but not in the presence of chloramphenicol or in a medium deficient in amino acids. However, the filament can divide to some extent in the presence of chloramphenicol if some protein synthesis is allowed to proceed at 30 C before the addition of the antibiotic. The elongated cells divide at 42 C provided that they are exposed to 30 C before being shifted to high temperature.


Analysis of octenylsuccinate rice and tapioca starches: Distribution of octenylsuccinic anhydride groups in starch granules.
Characterization of the fine structure of octenylsuccinic anhydride (OSA) starch would lead to a better understanding of functional properties. OSA rice and tapioca starches were analyzed using microscopy, liquid chromatography and nuclear magnetic resonance. Chain length distribution of amylopectin changed significantly (P<0.05) after OSA esterification. Weight averaged degree of polymerization (DPw) decreased significantly (P<0.05) from 16.47 to 13.29 and from 14.87 to 12.47 in native and OSA rice and tapioca starches, respectively. The chain length distribution of pure amylopectin fractions suggested that OSA groups were not present in the amylopectin portion of the starch. (1)H NMR analysis of pure amylose and amylopectin fractions indicated that OSA substitution was present only in amylose fractions of rice and tapioca starches. Esterification with 3% OSA results in starch that has OSA substituted mainly on amylose chains or possibly on amylopectin chains that have been hydrolyzed from the amylopectin molecules during esterification.


The downside of friendship: sources of strain in older women's friendships.
This article explores sources of strain in older women's friendships. We know a fair amount about the salutary effects of women's friendships, but little about sources of strain and tension. What we do know comes from quantitative studies where subjects respond to lists, categories, or sets of exchanges, not open-ended descriptions of conflict. This project begins to fill that gap by giving voice to older women's understandings of the downside of friendship. Twenty-six older women were intensively interviewed about their friendships and their responses were analyzed using grounded theory methodology. Strain was linked to disruption ofexpectations associated with friendship, including expectations that friends will: (1) share similar interests, personal habits, and friends; (2) be trustworthy; (3) be honest; (4) not exploit one another; (5) live close by; (6) not be overly dependent; (7) share similar social statuses; (8) not be "whiney or demanding" when ill; (9) maintain balance and reciprocity in their friendships; and (10) tease only for fun. Most older women chose to avoid conflict rather than to openly confront their friends when they felt hurt or disappointment.


Bromine Radical (Br• and Br2•-) Reactivity with Dissolved Organic Matter and Brominated Organic Byproduct Formation.
Dissolved organic matter (DOM) is a major scavenger of bromine radicals (e.g., Br• and Br2•-) in sunlit surface waters and during oxidative processes used in water treatment. However, the literature lacks quantitative measurements of reaction rate constants between bromine radicals and DOM and lacks information on the extent to which these reactions form brominated organic byproducts. Based on transient kinetic analysis with different fractions and sources of DOM, we determined reaction rate constants for DOM with Br• ranging from <5.0 × 107 to (4.2 ± 1.3) × 108 MC-1 s-1, which are comparable with those of HO• but higher than those with Br2•- (k = (9.0 ± 2.0) × 104 to (12.4 ± 2.1) × 105 MC-1 s-1). Br• and Br2•- attack the aromatic and antioxidant moieties of DOM via the electron transfer mechanism, resulting in Br- release with minimal substitution of bromine into DOM. For example, the total organic bromine was less than 0.25 μM (as Br) at environmentally relevant bromine radicals' exposures of ∼10-9 M·s. The results give robust evidence that the scavenging of bromine radicals by DOM is a crucial step to prevent inorganic bromine radical chemistry from producing free bromine (HOBr/OBr-) and subsequent brominated byproducts.


Physical properties of flexible ureteroscopes: implications for clinical practice.
Physical characteristics may be important in the performance of a flexible ureteroscope. This study evaluated the strength of the shaft and deflection mechanism of several instruments. Sequential loads were placed along the axis of downward deflection to measure the stiffness of the shaft and strength of deflection. Bending pressure was defined as the force required to deflect the tip of the ureteroscope 15 degrees from baseline. Buckling pressure was defined as the force that resulted in catastrophic bending (>90 degrees) of the shaft of the ureteroscope. Strength of deflection was defined as the force that resulted in loss of 10 degrees of active deflection. Bending pressures were lower for the Olympus URF-P3 (6.4 g) and Wolf 7325.172 (6.0 g) ureteroscopes. Similarly, buckling pressures were lower for these two ureteroscopes (9.0 g and 11.6 g, respectively). The Wolf and Storz flexible ureteroscopes had stronger deflection mechanisms than the Olympus URF-P3 and the ACMI DUR-8. This study demonstrates significant differences in ureteroscope strength. Higher buckling pressures may facilitate advancement of a ureteroscope over a guidewire but may impede secondary deflection. Lower bending pressures may facilitate passive intrarenal manipulation. Strength of deflection may impact the ability to maintain deflection with an instrument in the working channel.


Prenatal diagnosis of xeroderma pigmentosum and trichothiodystrophy in 76 pregnancies at risk.
Evaluation of results in a consecutive series of 76 prenatal diagnoses for xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) made since 1977. UV-induced DNA repair synthesis was assessed by the autoradiographic measurement of the incorporation of (3)H-thymidine. XP was diagnosed in 19 of the 76 investigated pregnancies at risk; cultured chorionic villus (CV) cells were used in 33 pregnancies with ten affected fetuses and cultured amniocytes in 43 pregnancies with nine affected fetuses. In four cases, CVS results were corroborated by subsequent investigation of amniocytes because maternal cell contamination in the CV cell culture was either present or could not be excluded. Uncertain results in two other cases with intermediate DNA repair capacity and severe maternal cell contamination required further investigation. Median time needed for cell culture and analysis was 25 days. To reduce intra-assay variations, a modification of the DNA repair synthesis assay has recently been developed. In this assay, patients and controls are investigated simultaneously in mixed cultures of cells labelled with polystyrene beads. Reliable prenatal diagnosis for XP and TTD can be made by the demonstration of clearly reduced UV-induced DNA repair synthesis due to defective global genome nucleotide excision repair.


Chemoradiotherapy for T3 and T4 squamous cell carcinoma of the esophagus using low-dose FP and radiation: a preliminary report.
We conducted this study to evaluate the clinical significance of preoperative concurrent chemoradiotherapy (CRT) followed by esophagectomy in the management of T3 and T4 esophageal cancer. Thirty patients with squamous cell carcinoma of the esophagus received CRT followed by surgery. Preoperative CRT consisted of 5-fluorouracil (500 mg/m(2) by 24 h infusion for 5 days), cisplatin (15 mg/m(2) on days 1-5), and concurrent radiotherapy (a total dose of 40 Gy delivered in daily fractions of 2 Gy, 5 times per week). Esophagectomy was planned for 4-6 weeks after treatment and restaging. All 30 patients completed preoperative CRT. A clinical response (PR+CR) of the primary tumor was obtained in 82.8%, and a response of metastatic nodes was seen in 23.1%. Radical resection was possible in 17 of 29 operated patients (58.6%). The postoperative mortality rate was 6.9%, and the hospital mortality rate was 10.3%. Ten out of 29 operated patients (34.5%) had no residual cancer in the resected esophagus, corresponding to pathological CR. The 1-year survival rate was 80.6%, the 2-year survival rate was 62.7%, and the 3-year survival rate was 53.8%. The clinical response group and the R0 or R1 group showed better survival than other patients. Preoperative CRT should be given to patients with squamous cell carcinoma, while esophagectomy remains the standard therapy for responders and has a tolerable mortality.


Intersubject and Interday Variability in Human Tear and Meibum Lipidomes: A Pilot Study.
Our aim was to quantitate day-to-day changes in the tear and meibum lipid profile of individual subjects in a pilot study of healthy humans. Matched tear and meibum samples were obtained from four subjects on three consecutive days. Quantitative lipid profiles of human basal tears and meibum were compared using multivariate analysis by principal components. Substantial differences in the lipid profile between subjects were observed, while lipid profiles were steady across the three consecutive days of sampling. Multivariate principal component analysis demonstrated that lysophosphatidylcholine was the largest variant lipid class between subjects in tears, while wax esters comprised the most variation between subjects in meibum secretions. Interday variability is shown to be much smaller than interpatient variability, suggesting that tears and meibum subjects both have unique profiles in humans.


Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease mice.
The precise cause of neuronal death in Huntington's disease (HD) is unknown. Although no single specific protein-protein interaction of mutant huntingtin has emerged as the pathologic trigger, transcriptional dysfunction may contribute to the neurodegeneration observed in HD. Pharmacological treatment using the histone deacetylase inhibitor sodium butyrate to modulate transcription significantly extended survival in a dose-dependent manner, improved body weight and motor performance, and delayed the neuropathological sequelae in the R6/2 transgenic mouse model of HD. Sodium butyrate also increased histone and Specificity protein-1 acetylation and protected against 3-nitropropionic acid neurotoxicity. Microarray analysis showed increased expression of alpha- and beta-globins and MAP kinase phosphatase-1 in sodium butyrate-treated R6/2 mice, indicative of improved oxidative phosphorylation and transcriptional regulation. These findings strengthen the hypothesis that transcriptional dysfunction plays a role in the pathogenesis of HD and suggest that therapies aimed at modulating transcription may target early pathological events and provide clinical benefits to HD patients.


Complete Vision Loss after Laparoscopic Hysterectomy.
Postoperative vision loss (POVL) is a rare but devastating complication that has only recently been reported following laparoscopic surgery. We present the case of a 34-year-old gravida 6 para 4 female who experienced POVL following an uncomplicated laparoscopic hysterectomy. Operating time was 174 minutes, and EBL was 75 mL. After surgery, she complained of complete vision loss with no light perception. No cerebral hemorrhage or ischemia was detected on imaging. Funduscopic exam revealed no structural abnormalities. On postoperative day 7, she received an IV methylprednisolone taper. The following morning, she reported mild light perception. Later that night, she reported a partial return of visual acuity and was discharged home. At her 2-week postoperative visit, her vision had returned to baseline. POVL is an emergency and prompt evaluation should be initiated to optimize outcome.


Gain-of-function mutation of chromatin regulators as a tumorigenic mechanism and an opportunity for therapeutic intervention.
Somatic gain-of-function mutations that drive cancer pathogenesis are well established opportunities for therapeutic intervention, as demonstrated by the clinical efficacy of kinase inhibitors in kinase-mutant malignancies. Here, we discuss the recently discovered gain-of-function mutations in chromatin-regulatory machineries that promote the pathogenesis of cancer. The current understanding of the underlying molecular mechanisms and the therapeutic potential for direct chemical inhibition will be reviewed. Point mutations that increase the catalytic activity of EZH2 and NSD2 histone methyltransferases are found in distinct subsets of B-cell neoplasms, which promote cell transformation by elevating the global level of H3K27 tri-methylation or H3K36 di-methylation, respectively. In addition, mutations in histone H3 have been identified in certain pediatric cancers which cause reprogramming of H3K27 and H3K36 methylation by interfering with the histone methyltransferase activity. Finally, chromosomal translocations involving chromatin regulator genes can lead to the formation of fusion oncoproteins that directly modify chromatin as their mechanism of action. Although relatively rare in aggregate, gain-of-function mutations in chromatin regulators represent compelling therapeutic targets in genetically defined subsets of cancer patients. However, a broader clinical impact for epigenetic therapies in oncology will require an increased understanding of how nonmutated chromatin regulators function as cancer-specific dependencies.


hsa-miR-206b Involves in the Development of Papillary Thyroid Carcinoma via Targeting LMX1B.
Papillary thyroid carcinoma (PTC) is the most common endocrine system malignant thyroid cancer, and patients with lymph node metastasis typically exhibit poor prognosis. MicroRNAs (miRNAs) can act as either oncogenes or tumor suppressors in PTC. This study was aimed at using PTC transcriptome data obtained from The Cancer Genome Atlas (TCGA) to identify differentially expressed, survival-related miRNAs and target genes. We analyzed the TCGA datasets to identify differentially expressed mRNAs/miRNAs in 493 PTC patients with stage I_II group (stages I and II) versus stage III_IV group (stages III and IV) according to TNM staging. The Kaplan-Meier survival analysis, the Cox regression analysis, and the log-rank test were performed to investigate survival-related miRNAs. We identified 36 significantly differentially expressed miRNAs in the stage I_II group versus the stage III_IV group, in which 31 were upregulated and only 5 were downregulated (i.e., hsa-miR-891a-5p, hsa-miR-892a, hsa-miR-888-5p, hsa-miR-891b, and hsa-miR-892b). Additionally, five signature miRNAs (hsa-miR-206, hsa-miR-299-3p, hsa-miR-299-5p, hsa-miR-496, and hsa-miR-509-3-5p) were associated with the overall survival of PTC patients. We also found that LMX1B, whose expression was inversely correlated with hsa-miR-206 expression, was a putative target gene of hsa-miR-206 and LMX1B was likely to serve as a tumor suppressor in PTC. hsa-miR-206b might be involved in promoting TNM staging in PTC via targeting of LMX1B.


Naloxone for heroin, prescription opioid, and illicitly made fentanyl overdoses: Challenges and innovations responding to a dynamic epidemic.
Community-based overdose prevention programs first emerged in the 1990's and are now the leading public health intervention for overdose. Key elements of these programs are overdose education and naloxone distribution to people who use opioids and their social networks. We review the evolution of naloxone programming through the heroin overdose era of the 1990's, the prescription opioid era of the 2000's, and the current overdose crisis stemming from the synthetic opioid era of illicitly manufactured fentanyl and its analogues in the 2010's. We present current challenges arising in this new era of synthetic opioids, including variable potency of illicit drugs due to erratic adulteration of the drug supply with synthetic opioids, potentially changing efficacy of standard naloxone formulations for overdose rescue, potentially shorter overdose response time, and reports of fentanyl exposure among people who use drugs but are opioid naïve. Future directions for adapting naloxone programming to the dynamic opioid epidemic are proposed, including scale-up to new venues and social networks, new standards for post-overdose care, expansion of supervised drug consumption services, and integration of novel technologies to detect overdose and deliver naloxone.


Colony stimulating factors and hemopoiesis.
Work in the past twenty years has led to the discovery of multiple families of hemopoietic growth factors that regulate the production and functional activity of the various subsets of blood cells. For granulocyte-monocyte populations, four such regulators (the colony stimulating factors GM-CSF, G-CSF, M-CSF and Multi-CSF) have been shown to interact to regulate these populations. Each has been purified, cDNA's for each have been cloned and mass-produced recombinant CSF's are becoming available for clinical use. Initial trials indicate that the CSF's will be valuable agents in stimulating hemopoiesis either following chemotherapy or marrow transplants or in stimulating resistance to life-threatening infections. CSF's play an important role in the development of myeloid leukemia but curiously can suppress myeloid leukemic populations because of their differentiation-inducing actions. However, it is still unclear whether the CSF's will prove of value in the management of particular myeloid leukemias.


Procedural sedation and analgesia for respiratory-gated MR-HIFU in the liver: a feasibility study.
Previous studies demonstrated both pre-clinically and clinically the feasibility of magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablations in the liver. To overcome the associated problem of respiratory motion of the ablation area, general anesthesia (GA) and mechanical ventilation was used in conjunction with either respiratory-gated energy delivery or energy delivery during induced apnea. However, clinical procedures requiring GA are generally associated with increased mortality, morbidity, and complication rate compared to procedural sedation and analgesia (PSA). Furthermore, PSA is associated with faster recovery and an increased eligibility for non- and mini-invasive interventions. In this study, we investigate both in an animal model and on a small patient group the kinetics of the diaphragm during free-breathing, when a tailored remifentanil/propofol-based PSA protocol inducing partial respiratory depression is used. Subsequently, we demonstrate in an animal study the compatibility of the resulting respiratory pattern of the PSA protocol with a gated HIFU ablation in the liver by direct comparison with gated ablations conducted under GA. Wilcoxon signed-rank tests were performed for statistical analysis of non-perfused and necrosed tissue volumes. Duty cycles (ratio or percentage of the breathing cycle with the diaphragm in its resting position, such that acoustic energy delivery with MR-HIFU was allowed) were statistically compared for both GA and PSA using student's t tests. In both animal and human experiments, the breathing frequency was decreased below 9/min, while maintaining stable vital functions. Furthermore an end-exhalation resting phase was induced by this PSA protocol during which the diaphragm is virtually immobile. Median non-perfused volumes, non-viable volumes based on NADH staining, and duty cycles were larger under PSA than under GA or equal. We conclude that MR-HIFU ablations of the liver under PSA are feasible and potentially increase the non-invasive nature of this type of intervention.


[Signet-ring cell carcinoma of the urinary bladder].
The signet-ring cell carcinoma of the urinary bladder as a rare histopathological variant of the adenocarcinoma is demonstrated with the help of clinical, cytological and histological findings of a case (29-year-old male) and it is referred to etiopathogenetic as well as clinical particularities which render possible a delimitation from the carcinoma of the epithelium of the urinary tract. Half of all 28 cases published up to now issued from the remaining parts of the urachus, particularly when localized in the parietal region. The from the first deeply infiltrating growth in the wall of the urinary bladder demands larger surgical interventions, in which cases the partial resection of the urinary bladder represents still the most insignificant operative procedure with clearly better prognosis. For improving the therapeutic situation and the dubious prognosis urachus carriers should be operated on in time, whereby for their recognition modern picture-producing diagnostic method such as sonography should be utilized.


Suppression of premature termination codons as a therapeutic approach.
In this review, we describe our current understanding of translation termination and pharmacological agents that influence the accuracy of this process. A number of drugs have been identified that induce suppression of translation termination at in-frame premature termination codons (PTCs; also known as nonsense mutations) in mammalian cells. We discuss efforts to utilize these drugs to suppress disease-causing PTCs that result in the loss of protein expression and function. In-frame PTCs represent a genotypic subset of mutations that make up ~11% of all known mutations that cause genetic diseases, and millions of patients have diseases attributable to PTCs. Current approaches aimed at reducing the efficiency of translation termination at PTCs (referred to as PTC suppression therapy) have the goal of alleviating the phenotypic consequences of a wide range of genetic diseases. Suppression therapy is currently in clinical trials for treatment of several genetic diseases caused by PTCs, and preliminary results suggest that some patients have shown clinical improvements. While current progress is promising, we discuss various approaches that may further enhance the efficiency of this novel therapeutic approach.


Smoking bans: influence on smoking prevalence.
This article reports trends in smoking prevalence and smoking restrictions in Canada since 2000, and examines associations between home and workplace restrictions and smoking cessation. Data are from the Canadian Tobacco Use Monitoring Survey and the longitudinal component of the National Population Health Survey. Trends in smoking prevalence and smoking restrictions were calculated. Associations between home and workplace smoking restrictions and smoking cessation were examined in the context of the Transtheoretical Model, which proposes that smokers go through five distinct stages in attempting to quit. The likelihood of current and former smokers being at specific stages was studied in relation to smoking restrictions at home and at work. Longitudinal data were used to determine if home and workplace smoking restrictions were predictors of quitting over a two-year period. Since 2000, Canadians smokers have faced a growing number of restrictions on where they can smoke. Bans at home and at work were associated with a reduced likelihood of being in the initial "stages of change," and an increased likelihood of being in the latter stages. Smokers who reported newly smoke-free homes or workplaces were more likely to quit over the next two years, compared with those who did not encounter such restrictions at home or at work.


Transcranial Doppler ultrasound in brain death: experience in 140 patients.
The interpretation of clinical tests for brain death is often complicated by the presence of facial trauma, or the use of barbiturate therapy for reduction of intracranial pressure. We propose a non-invasive technique--transcranial Doppler (TCD) sonography for the diagnosis of brain death. One hundred and forty comatose patients, 111 of whom were believed to be brain dead underwent TCD examinations. TCD assessments of the middle cerebral arteries (MCAs) and the basilar artery were performed before formal clinical testing for brain death. The TCD spectra recorded in the brain dead (BD) patients consisted of short, sharp systolic peaks followed by retrograde flow during diastole or just systolic peaks with absent flow in either direction. There were no survivors among patients who displayed these two TCD patterns. The 29 comatose control patients always showed flow throughout the cardiac cycle--no retrograde flow was ever recorded in these patients all of whom survived. Of particular interest were the basilar artery results. In nine BD patients no MCA signals could be obtained while good quality signals were recorded from the basilar artery. The TCD results agreed essentially with 100% accuracy with clinical testing and four vessel cerebral angiography. This paper illustrates the usefulness of TCD examination of the MCAs and especially the basilar artery in the diagnosis of brain death.


Nutritional support in children undergoing bone marrow transplantation.
Nutritional status and 'well-being' were compared prospectively in 39 children (mean age 8.1 years) who received nutritional support following bone marrow transplantion (BMT): 20 received enteral tube feeding (ETF; six received parenteral nutrition [PN] subsequently) and 19 with oral mucositis received PN (one received ETF subsequently). Poor nutritional status (height for age and/or weight for height and/or mid-arm circumference z-scores <-1) was present in 18 patients and was associated with a longer hospital stay (P = 0. 01). Both ETF and PN groups were comparable with respect to age, pretransplant nutritional status and conditioning regimens. No significant deterioration in anthropometric indices in either group occurred following BMT. However, significant correlations were found between the duration of ETF (and not PN) and improvements in nutritional status. Furthermore, PN was associated with more frequent exocrine pancreatic insufficiency than ETF (P = 0.001). Oral mucositis was associated with poorer 'well being' at the start of PN compared with ETF (P < 0.0001), but this was reversed by the end of PN. Bone marrow recovery, hospital stay and positive blood cultures were similar in the two groups. Hypomagnesaemia, hypophosphataemia and biochemical zinc deficiency were common in both groups but hypoalbuminaemia and biochemical selenium deficiency were worse in the PN group. In conclusion, both ETF and PN are effective in maintaining nutritional status post-BMT. When ETF is tolerated, it is associated with better nutritional response. With the existing ETF and PN regimens close monitoring of the trace element and mineral status is required.


[A case of systemic lupus erythematosus associated with thrombotic thrombocytopenic purpura and hemophagocytic syndrome].
A 44-year-old female. Developed polyarthralgia in August 2002. The patient was diagnosed with systemic lupus erythematosus (SLE) in November, due to polyarthralgia, leukopenia, anti ds-DNA antibody positive, antinuclear antibody positive, and false positive serologic test for syphilis. Hypocomplementemia continued even after the steroid treatment was conducted with insufficient control. In November 2003, ran fever and observed polyarthralgia. In December, gross hematuria and purpura appeared. The patient was hospitalized on December 25. Thrombotic thrombocytopenic purpura (TTP) was suspected from the emergence of fragmented red cells, hemolysis, thrombocytopenic purpura, headache, renal dysfunction and fever. As hemophagocytic syndrome (HPS) was suspected from hyper-ferritinemia, bone marrow aspiration was conducted. Macrophage confirmed hemophagocytic image and the patient was diagnosed with HPS complication. Methylprednisolone pulse therapy was conducted for three days, followed by the administration of prednisolone 60 mg. Plasma exchange therapy was also conducted from the first day of hospitalization. Recurrence of TTP after plasma exchange therapy, but it improved by additional plasma exchange. Low vWF-CP (ADAMTS-13) activity was observed in this case, and anti-vWF-CP antibody was positive. TTP and HPS are both critical intractable complications of SLE. Bearing in mind the possibility of simultaneous complication of both symptoms, prompt diagnosis is crucial for life-saving.


Frequency based feature selection method using whale algorithm.
Feature selection is the problem of finding the best subset of features which have the most impact in predicting class labels. It is noteworthy that application of feature selection is more valuable in high dimensional datasets. In this paper, a filter feature selection method has been proposed on high dimensional binary medical datasets - Colon, Central Nervous System (CNS), GLI_85, SMK_CAN_187. The proposed method incorporates three sections. First, whale algorithm has been used to discard irrelevant features. Second, the rest of features are ranked based on a frequency based heuristic approach called Mutual Congestion. Third, majority voting has been applied on best feature subsets constructed using forward feature selection with threshold τ = 10. This work provides evidence that Mutual Congestion is solely powerful to predict class labels. Furthermore, applying whale algorithm increases the overall accuracy of Mutual Congestion in most of the cases. The findings also show that the proposed method improves the prediction with selecting the less possible features in comparison with state of the arts. https://github.com/hnematzadeh.


Nectar sampling for prairie and oak savanna butterfly restoration.
Understanding floral resources is vital for restoring pollinators in habitats affected by anthropogenic development and climate change. As the primary adult food, nectar can limit butterfly longevity and reproduction. For pollinator restoration, it would therefore be useful to examine nectar resources. However, because many flowers preferred by butterflies are too small for microcapillary sampling and the potential for nectar contamination can make accurate measurement difficult, we developed a modified centrifugation method to extract and separate nectar and pollen. We sampled nectar from 19 forbs using a glass wool filter to exclude potentially contaminating pollen during centrifugation. To minimize costs, we measured sugar concentration by refractometry and simple ninhydrin tests for amino acids and improved test accuracy by subsequent image analysis. Artificial nectars were used to verify the new techniques. This method eliminated pollen from samples, while only slightly increasing sugar concentrations. Some amino acids were lost during centrifugation, but only samples with high concentrations exhibited substantial loss. We found significant differences in nectar quality among species, as well as an unexpected inverse relationship between amino acid and sugar concentrations. This modified centrifugation technique is an efficient, less damaging, inexpensive approach for collecting nectar from small flowers while eliminating pollen contamination, and will facilitate restoration of declining pollinators and thereby the plants they service.


Breast cancer early detection: A phased approach to implementation.
When breast cancer is detected and treated early, the chances of survival are very high. However, women in many settings face complex barriers to early detection, including social, economic, geographic, and other interrelated factors, which can limit their access to timely, affordable, and effective breast health care services. Previously, the Breast Health Global Initiative (BHGI) developed resource-stratified guidelines for the early detection and diagnosis of breast cancer. In this consensus article from the sixth BHGI Global Summit held in October 2018, the authors describe phases of early detection program development, beginning with management strategies required for the diagnosis of clinically detectable disease based on awareness education and technical training, history and physical examination, and accurate tissue diagnosis. The core issues address include finance and governance, which pertain to successful planning, implementation, and the iterative process of program improvement and are needed for a breast cancer early detection program to succeed in any resource setting. Examples are presented of implementation, process, and clinical outcome metrics that assist in program implementation monitoring. Country case examples are presented to highlight the challenges and opportunities of implementing successful breast cancer early detection programs, and the complex interplay of barriers and facilitators to achieving early detection for breast cancer in real-world settings are considered.


No evidence of association of the MYO9B polymorphisms with celiac disease in the Spanish population.
Inconsistent results concerning the association of polymorphisms in the MYO9B gene with celiac disease (CD) have been recently published. This gene encodes a myosin with a guanosine-triphosphatase (GTPase)-activating protein domain for the Rho-family of small G proteins, which are involved in cytoskeleton remodeling and therefore potentially involved in intestinal permeability. Functional and positional reasons led us to investigate the role of MYO9B polymorphisms in the Spanish CD population. A case-control study, including 415 CD patients and 433 ethnically matched healthy controls, and a familial study, including parents of 145 of those CD patients, was performed. Six MYO9B variants previously associated with CD were analyzed: rs2305767, rs2279003, rs962917, rs1457092, rs2305765 and rs2305764. No MYO9B variants or MYO9B haplotypes were found associated with CD, either before or after stratification of the patients for the human leucocyte antigen (HLA)-DQ2-positive risk factor. The family study revealed no distorted transmission of the aforementioned MYO9B polymorphisms or haplotypes. Our results support a negligible influence of this gene on CD predisposition.


Supplementingand activating blood circulation method to treat vertebrobasilar dolichoectasia with posterior circulatory watershed infarction: a case report of two patients.
Vertebrobasilar dolichoectasia (VBD), a rare posterior circulation vascular variant disease, is an important risk factor for many acute cerebrovascular diseases. An insufficient understanding of VBD often leads to misdiagnose. Two cases of VBD that were initially diagnosed as posterior circulation watershed infarction are reported here. Absence of common causes of stroke including hypoperfusion, blood system diseases, carotid and aortic dissection, and eosinophil elevation, the symptoms of the 2 patients met the diagnostic criteria of VBD. Both patients displayed symptoms that were in line with the Traditional Chinese Medicine (TCM) syndrome pattern of "deficiency and blood stasis". Accordingly, they were comprehensively treated with Supplementingand activating blood circulation method. The clinical manifestations of the 2 patients were remarkably improved and no recurrence of watershed infarction was found in a 1-year follow-up. A detailed medical history and laboratory examination are capable of improving diagnostic accuracy of VBD. TCM treatment based on syndrome identification might be a promising candidate for VBD management.


The economic burden of chronic obstructive pulmonary disease from 2004 to 2013.
This study examines the epidemiology and economic impact of chronic obstructive pulmonary disease (COPD) at a nationwide level in South Korea. This retrospective analysis used the societal cost-of-illness framework, consisting of direct medical costs, direct non-medical costs, and indirect costs. In order to analyze the societal costs of patients with COPD, this study used a data mining and a macro-costing method on data from a South Korean national-level health survey and a national health insurance claims database from 2004-2013. The total societal cost of COPD in 2013 was estimated to be $439.9 million for 1,419,914 patients. The direct medical cost for COPD was $214.3 million, which included a hospitalization cost of $96.3 million, an outpatient cost of $76.4 million, and a pharmaceutical cost of $41.6 million. The direct non-medical cost was estimated at $43.5 million. The indirect overall cost associated with the morbidity and mortality of COPD was $182.2 million in 2013. This study showed that COPD has a major effect on healthcare costs, particularly direct medical costs. Thus, appropriate long-term interventions are recommended to lower the economic burden of COPD in South Korea.


Aerolysin, a hemolysin from Aeromonas hydrophila, forms voltage-gated channels in planar lipid bilayers.
The cytolytic toxin aerolysin was found to form ion channels which displayed slight anion selectivity in planar lipid bilayers. In voltage-clamp experiments the ion current flowing through the channels was homogeneous indicating a defined conformation and a uniform size. The channels remained open between -70 to +70 mV, but outside this range they underwent voltage-dependent inactivation which was observed as open-closed fluctuations at the single-channel level. Zinc ions not only prevented the formation of channels by inhibiting oligomerization of monomeric aerolysin but they also induced a closure of preformed channels in a voltage-dependent fashion. The results of a Hill plot indicated that 2-3 zinc ions bound to a site within the channel lumen. Proaerolysin, and a mutant of aerolysin in which histidine 132 was replaced by an asparagine, were both unable to oligomerize and neither could form channels. This is evidence that oligomerization is a necessary step in channel formation.


On the use of hand-held magnifiers during reading.
Little is known about the actual use of magnifiers (or loupes) during reading. In studying the influence of the use of magnifiers on the reading process the reading field is a relevant factor. Four reading fields are distinguished: three horizontal reading fields and the vertical reading field. We examined the influence of a variation in the widths of these fields on the reading behavior of subjects. This was done by measuring two-dimensional loupe movements while subjects read text under conditions that provided a variety of reading field widths. It was found that individual subjects use different reading-field widths depending on loupe dimensions. Most difficulties in reading with a magnifier, especially finding the beginning of a new line, appear to result from the need to move the loupes horizontally in order to read the complete line of text.


Association between Dietary Share of Ultra-Processed Foods and Urinary Concentrations of Phytoestrogens in the US.
The aim of this study was to examine the relationship between dietary contribution of ultra-processed foods and urinary phytoestrogen concentrations in the US. Participants from cross-sectional 2009-2010 National Health and Nutrition Examination Survey aged 6+ years, selected to measure urinary phytoestrogens and with one 24-h dietary recall were evaluated (2692 participants). Food items were classified according to NOVA (a name, not an acronym), a four-group food classification based on the extent and purpose of industrial food processing. Ultra-processed foods are formulations manufactured using several ingredients and a series of processes (hence "ultra-processed"). Most of their ingredients are lower-cost industrial sources of dietary energy and nutrients, with additives used for the purpose of imitating sensorial qualities of minimally processed foods or of culinary preparations of these foods. Studied phytoestrogens included lignans (enterolactone and enterodiol) and isoflavones (genistein, daidzein, O-desmethylangolensin and equol). Gaussian regression was used to compare average urinary phytoestrogen concentrations (normalized by creatinine) across quintiles of energy share of ultra-processed foods. Models incorporated survey sample weights and were adjusted for age, sex, race/ethnicity, family income, and education, among other factors. Adjusted enterodiol geometric means decreased monotonically from 60.6 in the lowest quintile to 35.1 µg/g creatinine in the highest, while adjusted enterolactone geometric means dropped from 281.1 to 200.1 across the same quintiles, respectively. No significant linear trend was observed in the association between these quintiles and isoflavone concentrations. This finding reinforces the existing evidence regarding the negative impact of ultra-processed food consumption on the overall quality of the diet and expands it to include non-nutrients such as lignans.


HIV Infection Prevalence Significantly Intersects With COVID-19 Infection At the Area Level: A US County-Level Analysis.
Limited empirical evidence exists about the extent to which the current HIV epidemic intersects with COVID-19 infections at the area/geographic level. Moreover, little is known about how demographic, social, economic, behavioral, and clinical determinants are jointly associated with these infectious diseases. Contiguous US counties (N = 3108). We conducted a cross-sectional analysis and investigated the joint association between new HIV infection prevalence in 2018 and COVID-19 infections (January 22, 2020 and October 7, 2020) and explore the contribution of factors such as income inequality, binge drinking, and socioeconomic deprivation. We used Bayesian multivariate spatial models to estimate the cross-disease correlations between these diseases and identified hotspots, which we defined as a county with a posterior probability greater than 80% of being in the top decile of that disease. New HIV infection prevalence and COVID-19 infection moderately and significantly intersect [spatial correlation = 0.37, 95% credible interval (CrI) = 0.36-0.37]. Seventy-five counties, mostly in the south, were at elevated burden for HIV and COVID-19 infections. Higher income inequality was positively associated with both COVID-19 (relative risk 1.05, 95% CrI = 1.03-1.07) and HIV infection (relative risk = 1.12, 95% CrI = 1.09-1.15). We found that there is a considerable intersection between the current distribution of HIV burden with COVID-19 infections at the area level. We identified areas that federal funding and vaccination campaigns should prioritize for prevention and care efforts.


Periodontal tissue regeneration with PRP incorporated gelatin hydrogel sponges.
Gelatin hydrogels have been designed and prepared for the controlled release of the transforming growth factor (TGF-b1) and the platelet-derived growth factor (PDGF-BB). PRP (Platelet rich plasma) contains many growth factors including the PDGF and TGF-b1. The objective of this study was to evaluate the regeneration of periodontal tissue following the controlled release of growth factors in PRP. For the periodontal ligament cells and osteoblast, PRP of different concentrations was added. The assessment of DNA, mitochondrial activity and ALP activity were measured. To evaluate the TGF-β1 release from PRP incorporated gelatin sponge, amounts of TGF-β1 in each supernatant sample were determined by the ELISA. Transplantation experiments to prepare a bone defect in a rat alveolar bone were an implanted gelatin sponge incorporated with different concentration PRP. In DNA assay and MTT assay, after the addition of PRP to the periodontal ligament cells and osteoblast, the cell count and mitochondrial activity had increased the most in the group with the addition of 5 × PRP. In the ALP assay, after the addition of PRP to the periodontal ligament cells, the cell activity had increased the most in the group with the addition of 3 × PRP. In the transplantation, the size of the bone regenerated in the defect with 3 × PRP incorporated gelatin sponge was larger than that of the other group.


Comparison of hand assisted and standard laparoscopic radical nephroureterectomy for the management of localized transitional cell carcinoma.
Hand assisted laparoscopy affords the surgeon tactile sensation and blunt dissection, which are currently limited using the standard laparoscopic technique. Therefore, we compared standard and hand assisted laparoscopic radical nephroureterectomy for localized upper tract transitional cell carcinoma. The medical records of 27 patients who underwent standard (11) or hand assisted (16) laparoscopic radical nephroureterectomy between April 1998 and January 2001 were retrospectively reviewed. The parameters of efficacy, efficiency, safety and convalescence were compared. Mean patient age was 64 and 66 years (p = 0.72) in the standard and hand assisted groups, and the mean American Society of Anesthesiologists score was 2.5 and 2.7 (p = 0.64), respectively. All standard and 15 of the 16 hand assisted (94%) procedures were successfully completed via laparoscopy. Total operative time was more than 1 hour shorter for hand assisted than for laparoscopic radical nephroureterectomy (4.9 versus 6.1 hours, p = 0.055). Mean estimated blood loss was similar in the standard and hand assisted groups (190 and 201 ml., p = 0.78). In each group 1 patient required blood transfusion. Mean specimen weight was significantly higher in hand assisted cases (576 versus 335 gm., p = 0.036). Mean time to oral intake was similar in patients who underwent standard and hand assisted laparoscopic radical nephroureterectomy (13 and 20 hours, respectively, p = 0.45). The mean analgesic requirement was also similar (29 and 33 mg. morphine sulfate, respectively, p = 0.83). Mean hospital stay in uncomplicated cases was similar for standard and hand assisted surgery (2.9 and 2.5 days, respectively). Overall hospital stay in the 2 cohorts was also similar (3.3 and 4.5 days, respectively, p = 0.59). Four patients per group experienced postoperative complications. There were no deaths in the standard group but 1 patient (6%) in the hand assisted group died postoperatively. Mean time to partial and complete convalescence in the standard and hand assisted groups was 2.4 and 5.2, and 3.5 and 8.0 weeks, while mean followup was 27.4 and 9.6 months, respectively. Compared with standard laparoscopy hand assisted laparoscopy decreases operative time without significantly altering short-term parameters of convalescence. However, long-term convalescence after hand assisted laparoscopic radical nephroureterectomy is 1 to 3 weeks longer (p = 0.27). Longer followup in the hand assisted cohort is necessary to determine whether there are any differences in the 2 methods in regard to cancer control.


Exploring the potential of boron-doped nanographene as efficient charge transport and nonlinear optical material: A first-principles study.
Owing to their excellent electrochemical properties, graphenes found applications in several fields ranging from semiconductors, solar cells, field effect transistors, and nanoscale electronic devices as well as in nonlinear optical (NLO) applications. The structural features, electro-optical, charge transport and nonlinear optical properties of the boron-doped graphene (BG) compound 1 were studied using density functional theory methods The BG compound comprises a central electron deficient site of boron atoms, which can serve as electron acceptor while terminal alkoxy groups as donors leading to powerful donor-π-acceptor (D-π-A) configuration. The experimental crystal structure was successfully reproduced by optimized ground state geometry at PBE0/6-311G* level of theory for isolated molecule. The experimental lattice parameters, geometries, crystal presentation and alignment of molecules in the unit cells as well as their packing orientation of BG compound 1 was also efficiently reproduced by applying periodic boundary conditions (PBC) at PBE level. The comprehensive intramolecular charge transfer (CT) was realized from terminal rings of the HOMO to the electron deficient sites of boron atoms of the LUMO. The nature of BG compound 1 might be more towards hole transport even though its hole reorganization energy is twice than that of the electron one due to the significant higher hole transfer integral values. The superior hole transfer integrals and intrinsic mobility values of the BG compound 1 might lead remarkable hole transport contender as compared to many other organic materials. The narrow band gap, density of states profile, dielectric function, uniform conductivity functions and noteworthy electronic as well as CT properties revealed that the BG compound 1 might be proficient optoelectronic contestant having intermolecular CT as well as intramolecular CT with optimal stability. A comparison of static third-order polarizability <γ> of BG compound 1, as calculated in present investigation, was also performed with some standard NLO molecules as well as graphene nanoflakes. Moreover, longitudinal component γzzzz of parent compound has been found 12 and 4 times larger than those of previously reported open-shell poly aromatic hydrocarbons (PAH). Interestingly, by increasing the donor ability, i.e., introduction of C2H2PhNH2 groups in place of OC4H9 groups (BG compound 3) at terminal positions boosts the <γ> amplitude∼8 times than that of its parent BG compound 1.


Characterization of the phosphorylation state of natriuretic peptide receptor-C.
Many internalized receptors are known to be phosphorylated within their cytoplasmic domain. Natriuretic peptide receptor-C (NPR-C) is a covalent homodimer primarily involved in the internalization of bound ligand resulting in tissue uptake and degradation of natriuretic peptides. In this report, we have investigated the phosphorylation state of NPR-C receptors present at high level in rat aortic smooth muscle cells (RASM). 32P labeled cells, NPR-C purification and phosphoamino acid analysis clearly demonstrate that NPR-C exists as a phosphoprotein in RASM cells and that phosphorylation occurs exclusively on serine residues. Transient expression of bovine NPR-C in Cos-P cells of kidney origin confirmed that phosphorylation occurs within the cytoplasmic domain of the receptor. These results provide the first evidence for NPR-C phosphorylation as well as a model for future studies of its role in altering receptor function.