Current profile of Charcot-Marie-Tooth disease in Africa: A systematic review.
Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy characterised by a high clinical and genetic heterogeneity. While most cases were described in populations with Caucasian ancestry, genetic research on CMT in Africa is scant. Only a few cases of CMT have been reported, mainly from North Africa. The current study aimed to summarise available data on CMT in Africa, with emphasis on the epidemiological, clinical, and genetic features. We searched PubMed, Scopus, Web of Sciences, and the African Journal Online for articles published from the database inception until April 2021 using specific keywords. A total of 398 articles were screened, and 28 fulfilled our selection criteria. A total of 107 families totalling 185 patients were reported. Most studies were reported from North Africa (n = 22). The demyelinating form of CMT was the commonest subtype, and the phenotype varied greatly between families, and one family (1%) of CMT associated with hearing impairment was reported. The inheritance pattern was autosomal recessive in 91.2% (n = 97/107) of families. CMT-associated variants were reported in 11 genes: LMNA, GDAP1, GJB1, MPZ, MTMR13, MTMR2, PRX, FGD4/FRABIN, PMP22, SH3TC2, and GARS. The most common genes reported are LMNA, GDAP1, and SH3TC2 and have been found mostly in Northern African populations. This study reveals that CMT is not rare in Africa, and describes the current clinical and genetic profile. The review emphasised the urgent need to invest in genetic research to inform counselling, prevention, and care for CMT in numerous settings on the continent.


The sociocultural relationships of older immigrant Punjabi women living in Nova Scotia: Implications for well-being.
With the increase of South Asian immigrants in Canada, the relationship between older immigrant Punjabi women's sociocultural relationships and their mental health and well-being needs to be understood. Guided by the social determinants of health and intersectional feminist frameworks, five Punjabi women living in Nova Scotia, Canada were interviewed. Three themes were identified: (a) having freedom yet being dependent on families, (b) conflating having a happy family with having good mental health, and (c) needing ways to connect with other older Punjabi women. These findings articulate how Punjabi relationships affect women's views on mental health and well-being.


Vasodilatation by acetylcholine is endothelium-dependent: a study by sonomicrometry in canine femoral artery in vivo.
External diameter of the femoral artery was measured by sonomicrometry in the anaesthetized dog. Intra-arterial acetylcholine lowered arterial pressure and thereby passively lowered diameter. When blood flow and distal resistance were controlled by roller pump and Starling resistor respectively, acetylcholine (0.1-10 microM) and substance P (0.1-1 nM) both caused up to 10% increase in diameter. Removal of endothelium by mechanically rubbing the artery lumen abolished the dilator response to acetylcholine and substance P but did not affect the response to nitroprusside. Constrictor responses to noradrenaline were unaltered by endothelium removal. Topical application of acetylcholine and substance P onto the adventitial surface of the artery also caused an increase in diameter but both agents were 50-100 times less potent by this route compared with intra-arterial infusion. These dilator responses were abolished by endothelium removal. In these circumstances acetylcholine caused constriction. We conclude that acetylcholine and substance P require an intact endothelium to elicit vasodilatation in vivo, at least for the large femoral artery. The results from the topical application experiments suggest that local neural release of vasoactive substances such as acetylcholine and substance P depend on an intact endothelium to cause vasodilatation.


Neuron differentiation and axon growth in the developing wing of Drosophila melanogaster.
Sensory neurons in the wing of Drosophila originate locally from epithelial cells and send their axons toward the base of the wing in two major bundles, the L1 and L3 nerves. We have estimated the birth times of a number of identified wing sensory neurons using an X-irradiation technique and have followed the appearance of their somata and axons by means of an immunohistochemical stain. These cells become immunoreactive and begin axon growth in a sequence which mirrors the sequence of their birth times. The earliest ones are born before pupariation and begin axonogenesis within 1 to 2 hr after the onset of metamorphosis; the last are born and differentiate some 12 to 14 hr later. The L1 and L3 nerves are formed in sections, with specific neurons pioneering defined stretches of the pathways during the period between 0 and 4 hr after pupariation (AP), and finally joining together around 12 hr AP. By 16 hr AP the adult complement of neurons is present and the adult peripheral nerve pattern has been established. Pathway establishment appears to be specified by multiple cues. In places where neurons differentiate in close proximity to one another, random filopodial exploration followed by axon growth to a neighboring neuron soma might be the major factor leading to pathway construction. In other locations, filopodial contact between neighboring somata does not appear to occur, and axon pathways joining neural neighbors by the most direct route are not established. We propose that in these cases additional factors, including veins which are already present at the time of axonogenesis, influence the growth of axons through non-neural tissues.


Analysis of the attraction of haemocytes from Mytilus edulis by molecules of bacterial origin.
Boyden chamber assays were performed to test the stimulatory effect of different bacterial products on the migratory activity of Mytilus haemocytes. The results indicate that these blood cells exhibit chemotactic as well as chemokinetic reactions. Lipopolysaccharides (LPS) from both Serratia marcescens and Escherichia coli stimulated the migration of cells through the membrane of the Boyden chamber when LPS was present in the lower compartment only. In contrast, addition of LPS to the lower as well as to the upper chamber did not increase the rate of migrating cells. Thus, LPS seemed to act as a chemotaxis-stimulating substance. Further analysis indicated that complete LPS molecules are required for cell stimulation because this did not occur when either the lipid or polysaccharide moieties of LPS were tested alone. Unlike LPS, the formylated tripeptide N-FMLP stimulated random cell migration. The peptide, which is released by bacteria, induced a higher haemocyte motility when present in both wells of the Boyden chamber than in tests where it was added to the lower compartment only. This chemokinetic response was not stimulated by the tetrapeptide N-FMLPLys. These findings demonstrate that bacterial products may elicit chemotactic and/or chemokinetic reactions in haemocytes from an invertebrate, and that the type of reaction that occurs is dependent upon the nature of the molecules presented.


Novel nasal niosomes loaded with lacosamide and coated with chitosan: A possible pathway to target the brain to control partial-onset seizures.
This work aimed to develop and produce lacosamide-loaded niosomes coated with chitosan (LCA-CTS-NSM) using a thin-film hydration method and the Box-Behnken design. The effect of three independent factors (Span 60 amount, chitosan concentration, and cholesterol amount) on vesicle size, entrapment efficiency, zeta potential, and cumulative release (8 h) was studied. The optimal formulation of LCA-CTS-NSM was chosen from the design space and assessed for morphology, in vitro release, nasal diffusion, stability, tolerability, and in vivo biodistribution for brain targeting after intranasal delivery. The vesicle size, entrapment, surface charge, and in vitro release of the optimal formula were found to be 194.3 nm, 58.3%, +35.6 mV, and 81.3%, respectively. Besides, it exhibits sustained release behavior, enhanced nasal diffusion, and improved physical stability. Histopathological testing revealed no evidence of toxicity or structural damage to the nasal mucosa. It demonstrated significantly more brain distribution than the drug solution. Overall, the data is encouraging since it points to the potential for non-invasive intranasal administration of LCA as an alternative to oral or parenteral routes.


Sequence of a pyrimidine-selective Na+/nucleoside cotransporter from pig kidney, pkCNT1.
A 3 kb cDNA called pkCNT1, a new member of the Na+/nucleoside cotransporter family, was cloned from pig kidney and sequenced. The sequence of pkCNT1 encodes a 647 amino acid protein that is 84% identical to the sequence of the rat pyrimidine-selective Na+/nucleoside cotransporter, rCNT1. pkCNT1 transports pyrimidines, such as thymidine and uridine, and has a Km for uridine of 9 microM.


Dichotomic Dearomatizations of Benzene vs Pyridine Rings of Sulfonyloxypyridine via (3 + 2) Cycloaddition.
Electron-poor arenesulfonyloxypyridines are selectively dearomatized whether on the pyridine or on the phenyl group through 1,3-dipolar cycloaddition (1,3-DC) involving non-stabilized azomethine ylides (AMY). Electronic effects of substituents on the aromatic rings allow to induce the regioselectivity of the transformation. Novel pyrrolidinic polycyclic heterocycles are thereby produced under mild acidic conditions at room temperature.


Treatment of lung cancer in older patients.
Lung cancer is a disease of older persons. It is the most common cause of cancer death in men and women in the United States. A comprehensive evaluation of medical comorbidities and functional status is important in all patients but perhaps more so in older adults, and it should be included in the assessment of older patients who have lung cancer. Age, per se, should not be a limiting factor to treatment, because a large body of evidence demonstrates that fit older patients who have lung cancer can safely undergo the same treatments as their younger counterparts with equally good results.


Male-Female Differences in Knee Laxity and Stiffness: A Cadaveric Study.
It has been reported that over 70% of anterior cruciate ligament (ACL) injuries occur in noncontact situations and that females are at 2 to 8 times greater risk of ACL injury than males. Increased joint laxity and reduced knee stiffness in female knees have been suggested as possible explanations for the higher ACL injury rates in females. Compared with male knees, female knees will demonstrate increased laxity and reduced stiffness along the anterior-posterior (AP), internal-external (IE), and varus-valgus (VV) directions. Controlled laboratory study. Forty-seven fresh-frozen human cadaveric knees were tested (22 male and 25 female) by use of a robotic system. Mean ages were 34.6 years (range, 19-45 years) for males and 28.4 years (range, 16-42 years) for females. Joint laxity and stiffness were measured from force-vs-displacement or torque-vs-rotation curves recorded for 3 modes of testing: ± 134 N AP force, ± 5 N · m IE torque, and ± 10 N · m VV moment. Compared with male knees, female knees had greater internal laxity from 0° to 50° flexion (P < .01; maximum difference of 8.3° at 50° of flexion) and greater valgus laxity from 0° to 50° of flexion (P < .05; maximum difference of 1.6° at 50° of flexion). However, female knees exhibited greater anterior laxity only at 50° of flexion (P < .03; difference of 1.3 mm). No significant male-female differences in anterior or posterior stiffness were found. Male knees had 42% greater internal stiffness from 0° to 30° of flexion (P < .03), 35% greater valgus stiffness at 10° of flexion (P < .03), and 19% greater varus stiffness at 50° of flexion (P < .03). Female knees demonstrated significantly increased laxity and reduced stiffness compared with males. This finding was not uniform but was dependent on the direction tested and the knee flexion angle. Understanding the risk factors for noncontact ACL injury is important for injury prevention. In combination with other female-specific risk factors, increased knee laxity may be a contributing factor associated with the higher rate of female ACL injuries.


Age at autism spectrum disorder diagnosis: A systematic review and meta-analysis from 2012 to 2019.
We currently assume that the global mean age at diagnosis of autism spectrum disorder ranges from 38 to 120 months. However, this range is based on studies from 1991 to 2012 and measures have since been introduced to reduce the age at autism spectrum disorder diagnosis. We performed a systematic review and meta-analysis (statistical analysis that combines the results of multiple scientific studies) for studies published between 2012 and 2019 to evaluate the current age at autism spectrum disorder diagnosis. We included 56 studies that reported the age at diagnosis for 40 countries (containing 120,540 individuals with autism spectrum disorder). Results showed the current mean age at diagnosis to be 60.48 months (range: 30.90-234.57 months) and 43.18 months (range: 30.90-74.70 months) for studies that only included children aged ⩽10 years. Numerous factors that may influence age at diagnosis (e.g. type of autism spectrum disorder diagnosis, additional diagnoses and gender) were reported by 46 studies, often with conflicting or inconclusive results. Our study is the first to determine the global average age at autism spectrum disorder diagnosis from a meta-analysis. Although progress is being made in the earlier detection of autism spectrum disorder, it requires our constant attention.


Early left ventricular systolic and diastolic dysfunction in patients with newly diagnosed obstructive sleep apnoea and normal left ventricular ejection fraction.
The aim of the study was to evaluate whether obstructive sleep apnea (OSA) contributes directly to left ventricular (LV) diastolic and regional systolic dysfunction in newly diagnosed OSA with normal left ventricle ejection fraction. 125 consecutive patients were prospectively enrolled in the study. Control group consisted of 78 asymptomatic age-matched healthy subjects who did not have any cardiovascular and respiratory diseases. All patients had undergone overnight polysomnography and standard transthoracic and tissue Doppler imaging echocardiogram. The E/A ratio and the peak E wave at mitral flow were significantly lower and the peak A wave at mitral flow was significantly higher in OSA patients compared with control subjects. Left ventricle isovolumetric relaxation time (IVRT) and mitral valve flow propagation (MVFP) were significantly longer in OSA patients than in controls. Tissue Doppler derived S' amplitude of lateral part at mitral valve (S'Lm) and E' wave amplitudes both at the lateral (E'Lm) and septal parts of the mitral valve (E'Sm) were significantly lower in OSA patients compared to controls. Newly diagnosed OSA patients with normal global LV function have significantly impaired diastolic function and regional longitudinal systolic function. OSA is independently associated with these changes in LV function.


The second decade of experience with the umbilical vein graft for lower-limb revascularization.
Some 20 years have elapsed since the initial concept and development of the human umbilical vein graft. Experience with 1074 umbilical vein grafts forms the basis of this report as the indications for this prosthesis have been refined and its performance defined. In 1988, the author and colleagues published their 10-year experience with umbilical vein which described the results of 907 bypasses constructed in 715 patients (799 limbs). Over the past 5 years, the use of umbilical vein has decreased because of a commitment to autologous saphenous vein. A total of 167 additional umbilical vein bypasses were performed at Englewood Hospital and Medical Center between 1985 and June 1993. Secondary patency rates for popliteal and crural reconstructions at 5 years showed a trend of continuous improvement--65% and 45% respectively compared with 57% and 33% as reported during the first decade of experience. Rates of infection, stenosis and pseudoaneurysm decreased and only two aneurysms have been discovered during this period. Umbilical vein is an acceptable alternative to the absent or deficient autologous vein. Patency rates are second only to autologous vein rates and the fear of failure due to aneurysm formation has not only been overstated, but also significantly exaggerated.


The monoamine stabilizer (-)-OSU6162 counteracts downregulated dopamine output in the nucleus accumbens of long-term drinking Wistar rats.
We recently established that the monoamine stabilizer (-)-OSU6162 (OSU6162) decreased voluntary alcohol-mediated behaviors, including alcohol intake and cue/priming-induced reinstatement, in long-term drinking rats, while blunting alcohol-induced dopamine output in the nucleus accumbens (NAc) of alcohol-naïve rats. Therefore, we hypothesized that OSU6162 attenuates alcohol-mediated behaviors by blunting alcohol's rewarding effects. Here, we evaluated the effects of long-term drinking and OSU6162 treatment (30 mg/kg, sc) on basal and alcohol-induced (2.5 g/kg, ip) NAc dopamine outputs in Wistar rats after 10 months of intermittent access to 20% alcohol. The results showed that basal and alcohol-induced NAc dopamine outputs were significantly lower in long-term drinking rats, compared with alcohol-naïve rats. In the long-term drinking rats, OSU6162 slowly increased and maintained the dopamine output significantly elevated compared with baseline for at least 4 hours. Furthermore, OSU6162 pre-treatment did not blunt the alcohol-induced output in the long-term drinking rats, a finding that contrasted with our previous results in alcohol-naïve rats. Finally, OSU6162 did not induce conditioned place preference (CPP) in either long-term drinking or alcohol-naïve rats, indicating that OSU6162 has no reinforcing properties. To verify that the CPP results were not due to memory acquisition impairment, we demonstrated that OSU6162 did not affect novel object recognition. In conclusion, these results indicate that OSU6162 attenuates alcohol-mediated behaviors by counteracting NAc dopamine deficits in long-term drinking rats and that OSU6162 is not rewarding on its own. Together with OSU6162's beneficial side-effect profile, the present study merits evaluation of OSU6162's clinical efficacy to attenuate alcohol use in alcohol-dependent patients.


Techniques to Determine the Effects of Jasmonates on Root Hydraulic Conductivity.
Plants subjected to drought and saline stress conditions suffer from tissue dehydration. Such dehydration is caused by the imbalance between root water uptake by roots and water loss by transpiration. Therefore, determination of root hydraulic properties is crucial to understand plant water balance. Root hydraulic conductivity (L) can be used to estimate root water transport capacity. L depends on root architecture (length and diameter of the root and proliferation of secondary roots), radial water transport pathway (root xylem vessels, plasmodesmata, apoplastic space, caspary bands), and on intrinsic membrane permeability to water (aquaporins, water membrane protein channels). Different methods have been developed to measure L, such as Pressure Chamber, Free Exudation, High-Pressure Flowmeter (HPFM), and Root Pressure Probe (RPP). In this chapter, we will focus on Pressure Chamber, Free Exudation, and HPFM methods which have been used to determine the effect of jasmonates (JA) on root hydraulic conductivity.


Pediatric tuberculosis outcomes and factors associated with unfavorable treatment outcomes in Botswana, 2008-2019: a retrospective analysis.
Globally, the amount of research on the outcomes of pediatric tuberculosis (TB) is disproportionately less than that of adult TB. The diagnosis of paediatric TB is also problematic in developing countries. The aim of this study was to describe the outcomes of pediatric TB in Botswana and to identify the factors associated with unfavorable outcomes. This was a retrospective analysis of pediatric TB outcomes in Botswana, over a 12-year period from January 2008 to December 2019. Treatment success (treatment completion or cured) was considered a favorable outcome, while death, loss to follow-up and treatment failure were considered unfavorable outcomes. Program data from drug-sensitive TB (DS-TB) cases under the age of 15 years were included. Sampling was exhaustive. Binary logistic regression was used to determine the factors associated with unfavorable outcomes during TB treatment. A p value of < 0.05 was considered a statistically significant association between the predictor variables and unfavorable outcomes. The data of 6,004 paediatric TB cases were extracted from the Botswana National TB Program (BNTP) electronic registry and analyzed. Of these data, 2,948 (49.4%) were of female patients. Of the extracted data, 1,366 (22.8%) were of HIV positive patients and 2,966 (49.4%) were of HIV negative patients. The rest of the data were of patients with unknown HIV status. Pulmonary TB accounted for 4,701 (78.3%) of the cases. Overall, 5,591 (93.1%) of the paediatric TB patient data showed treatment success, 179 (3.0%) were lost to follow-up, 203 (3.4%) records were of patients who died, and 31 (0.5%) were of patients who experienced treatment failure. The factors associated with unfavorable outcomes were positive HIV status (AOR 2.71, 95% CI: 2.09-3.52), unknown HIV status (AOR 2.07, 95% CI: 1.60-2.69) and retreatment category (AOR 1.92, 95% CI: 1.30-2.85). Compared with the 0-4 years age category, the 5-9 years (AOR 0.62, 95% CI: 0.47-0.82) and 10-14 years (AOR 0.76, 95% CI: 0.60-0.98) age categories were less likely to experience the unfavorable outcomes. This study shows a high treatment success rate among paediatric TB cases in Botswana. The government under the National TB Program should maintain and consolidate the gains from this program. Public health interventions should particularly target children with a positive or unknown HIV status, those under 5 years, and those who have been previously treated for TB.


Pulmonary artery rupture as a complication of Swan-Ganz catheter application. Diagnosis and endovascular treatment: a single centre's experience.
The placement of a Swan-Ganz catheter into the pulmonary artery may lead to a number of complications (2-17%). In less than 0.2% of cases Swan-Ganz catheterization results in serious vascular damage - pulmonary artery rupture (PAR). This paper presents two distinct forms of iatrogenic PAR treated endovascularly using different vascular devices. To evaluate the effectiveness of endovascular treatment and the application of different types of vascular devices in the management of pulmonary artery rupture caused by Swan-Ganz catheterization. In this retrospective study we evaluated 2 patients in whom Swan-Ganz catheter application was used for perioperative monitoring and resulted in pulmonary artery rupture. This complication was treated endovascularly by means of interventional cardiology. We report the cases of 2 patients with a pulmonary artery pseudoaneurysm formed in the perioperative period. In case 1, a single, 4-loop, 3 mm diameter coil was implanted. In case 2, a 5 mm Amplatzer Vascular Plug IV was applied. In both cases, the endovascular approach resulted in total occlusion of the feeding artery and reduced further extravasation of the blood. Despite its extremely low incidence, iatrogenic PAR is a serious, life-threatening complication of Swan-Ganz catheterization that requires urgent attention. Among available methods of treatment, percutaneous embolization is a relatively quick, safe, accurate and highly effective alternative to traumatizing surgery.


A novel amperometric immunosensor based on layer-by-layer assembly of gold nanoparticles-multi-walled carbon nanotubes-thionine multilayer films on polyelectrolyte surface.
A highly sensitive and label-free amperometric immunosensor has been developed for the detection of carcinoembryonic antigen (CEA) based on layer-by-layer (LBL) assembly of gold nanoparticles (GNPs), multi-walled carbon nanotubes-thionine (MWNTs-THI) and chitosan (CHIT) on 3-mercaptopropanesulfonic, sodium salt (MPS)-modified gold electrode surface by electrostatic adsorption. The stepwise LBL assembly process of electroactive species on electrode surface was characterized by means of cyclic voltammetry (CV) in PBS. The factors influencing the performance of the resulting immunosensor were studied in detail. The morphologies of MWNTs, MWNTs-THI and GNPs-MWNTs-THI-CHIT were further characterized by transmission electron microscopy (TEM). The immunosensor was highly sensitive to CEA with a detection limit of 0.01 ng mL(-1) (signal/noise ratio of 3) and the linear range with two concentration intermittences was from 0.5 to 15.0 ng mL(-1) and from 15.0 to 200.0 ng mL(-1), respectively. In addition, the prepared immunosensor could be regenerated 10 times with 5 M urea solution. When the immunosensor was stored at 4 degrees C and measured intermittently (every 4-6 days), no apparent change was found over 3 months. The immunosensor system showed an excellent reproducibility and stability.


Pharyngocutaneous Fistula in Salvage Laryngectomy: Use of the Stapler Versus Manual Suturing Technique.
A pharyngocutaneous fistula (PCF) is the most common complication after salvage total laryngectomy (STL) with an incidence ranging from 5 to 73%, causing an increase in morbidity and delaying the patient's recovery. A surgical technique to prevent PCF formation is the use of the stapler to suture the pharyngeal mucosa. We have reviewed the medical files of 91 patients who had undergone STL, dividing the patients into two groups (manual suture vs. stapler), based on the type of pharyngeal suture performed during the STL. We found 12/49 (24.5%) cases of a PCF in group A (manual) and 5/42 (11.9%) cases of a PCF in group B (stapler). There is a statistically significant difference between the two groups with the patients in group B presenting better results in terms of the reduction of the surgical time, the length of the hospital stay and also in the restarting of oral feeding. The advantages of mechanical suturing with the stapler are reduced surgical times, a lower PCF formation rate, which involves an early removal of the nasogastric tube, and reduced hospitalization times. Further studies with a larger case series will be necessary to confirm the results obtained and to standardize the surgical technique.


Childhood obesity in secondary care: national prospective audit of Australian pediatric practice.
In many countries, pediatricians offer skilled secondary care for children with conditions more challenging than can readily be managed in the primary care sector, but the extent to which this sector engages with the detection and management of obesity remains largely unexplored. This study aimed to audit the prevalence, diagnosis, patient, and consultation characteristics of obesity in Australian pediatric practices. This was a national prospective patient audit in Australia. During the course of 2 weeks, members of the Australian Paediatric Research Network prospectively recorded consecutive outpatient consultations by using a brief standardized data collection form. Measures included height, weight, demographics, child and parent health ratings, diagnoses, referrals, investigations, and consultation characteristics. We compared the prevalence of pediatrician-diagnosed and measured obesity (body mass index ≥95th percentile) and top-ranked diagnoses, patient, and consultation characteristics in (a) obese and nonobese children, and (b) obese children with and without a diagnosis. A total of 198 pediatricians recorded 5466 consultations with 2-17 year olds, with body mass index z-scores calculated for 3436 (62.9%). Of the 12.6% obese children, only one-third received an "overweight/obese" diagnosis. Obese children diagnosed as overweight/obese were heavier, older, and in poorer health than those not diagnosed and incurred more Medicare (government-funded health system) cost and referrals. Obesity is infrequently clinically diagnosed by Australian pediatricians and measurement practices vary widely. Further research could focus on supporting and normalizing clinical obesity activities from which pediatricians and parents could see clear benefits.


Novel insights into ChREBP regulation and function.
Glucose is an energy source that also controls the expression of key genes involved in energetic metabolism through the glucose-signaling transcription factor carbohydrate response element-binding protein (ChREBP). ChREBP has recently emerged as a central regulator of glycolysis and de novo fatty acid synthesis in liver, but new evidence shows that it plays a broader and crucial role in various processes, ranging from glucolipotoxicity to apoptosis and/or proliferation in specific cell types. However, several aspects of ChREBP activation by glucose metabolites are currently controversial, as well as the effects of activating or inhibiting ChREBP, on insulin sensitivity, which might depend on genetic, dietary or environmental factors. Thus, much remains to be elucidated. Here, we summarize our current understanding of the regulation and function of this fascinating transcription factor.


Methadone initiation in a bridge clinic for opioid withdrawal and opioid treatment program linkage: a case report applying the 72-hour rule.
In the United States, methadone for opioid use disorder (OUD) is limited to highly regulated opioid treatment programs (OTPs), rendering it inaccessible to many patients. The "72-hour rule" allows non-OTP providers to administer methadone for emergency opioid withdrawal management while arranging ongoing care. Low-barrier substance use disorder (SUD) bridge clinics provide rapid access to buprenorphine but offer an opportunity to treat acute opioid withdrawal while facilitating OTP linkage. We describe the case of a patient with OUD who received methadone for opioid withdrawal in a bridge clinic and linked to an OTP within 72 h. A 54-year-old woman with severe OUD was seen in a SUD bridge clinic requesting OTP linkage and assessed with a clinical opiate withdrawal scale (COWS) score of 12. She reported daily nasal use of 1 g heroin/fentanyl. Prior OUD treatment included buprenorphine-naloxone, which was only partially effective. Her acute opioid withdrawal was treated with a single observed oral dose of methadone 20 mg. She returned the following day with persistent opioid withdrawal (COWS score 11) and was treated with methadone 40 mg. On day 3, the patient was successfully admitted to a local OTP, where she remained engaged 3 months later. While patients continue to face substantial access barriers, bridge clinics can play an important role in treating opioid withdrawal, building partnerships with OTPs to initiate methadone on demand, and preventing life-threatening delays to methadone treatment. Federal policy reform is urgently needed to make methadone more accessible to people with OUD.


Evaluation of texture for classification of abdominal aortic aneurysm after endovascular repair.
The use of the endovascular prostheses in abdominal aortic aneurysm has proven to be an effective technique to reduce the pressure and rupture risk of aneurysm. Nevertheless, in a long-term perspective, complications such as leaks inside the aneurysm sac (endoleaks) could appear causing a pressure elevation and increasing the danger of rupture consequently. At present, computed tomographic angiography (CTA) is the most common examination for medical surveillance. However, endoleak complications cannot always be detected by visual inspection on CTA scans. The investigation on new techniques to detect endoleaks and analyse their effects on treatment evolution is of great importance for endovascular aneurysm repair (EVAR) technique. The purpose of this work was to evaluate the capability of texture features obtained from the aneurysmatic thrombus CT images to discriminate different types of evolutions caused by endoleaks. The regions of interest (ROIs) from patients with different post-EVAR evolution were extracted by experienced radiologists. Three techniques were applied to each ROI to obtain texture parameters, namely the grey level co-occurrence matrix (GLCM), the grey level run length matrix (GLRLM) and the grey level difference method (GLDM). The results showed that GLCM, GLRLM and GLDM features presented a good discrimination ability to differentiate between favourable or unfavourable evolutions. GLCM was the most efficient in terms of classification accuracy (93.41% ± 0.024) followed by GLRLM (90.17% ± 0.077) and finally by GLDM (81.98% ± 0.045). According to the results, we can consider texture analysis as complementary information to classified abdominal aneurysm evolution after EVAR.


The impact of Triton WR-1339 induced hyperlipidemia on the effects of benzo(a)pyrene or guaiacol on α- and γ-tocopherol pools and selected markers of pro-/antioxidative balance in rat plasma and erythrocytes.
The toxicity of carcinogenic benzo(a)pyrene (BaP) can be intensified by the pro-oxidative effects of metabolic activation. The oxidatively active products can be formed during enzymatic biotransformation or in the process of co-oxygenation with lipid peroxidation. This study assesses if the acute hyperlipidemia can increase pro-oxidative effects of BaP as a factor intensifying processes of lipid peroxidation and co-oxygenation. After three days of i.p. administration of BaP or guaiacol (equimolar dose 10mg/kg b.w.) without or with the hyperlipidemia inducer-Triton WR-1339 to male Wistar rats, the levels of α- and γ-tocopherol were measured in erythrocytes and plasma together with the level of lipid peroxidation as malonyldialdehyde (MDA) concentration. Guaiacol was chosen as a reference substance due to its high ability to co-oxygenate. Additionally, the activity of superoxide dismutase (Cu,ZnSOD) in erythrocytes and plasma was monitored. In normolipaemic groups the significant decrease in erythrocyte α-tocopherol pool and the increase in lipid peroxidation level were observed after BaP or guaiacol administration. In hyperlipaemic groups, despite the increase in the level of lipid peroxidation, there were no additional effects in tocopherol pools compared to the normolipaemic groups which could be attributed to co-oxygenation. Decrease of α-tocopherol in erythrocytes was proportional to the reduction in normolipemic subjects when accounting for the migration to hyperlipemic plasma. There was no co-oxygenation effect on the activity of superoxide dismutase (Cu,ZnSOD) in blood.


Aerobic biological degradation of organic matter and fracturing fluid additives in high salinity hydraulic fracturing wastewaters.
Reuse of hydraulic fracturing wastewaters depends on effective tailored treatment to prepare the water for the intended end use. Aerobic biological treatment of hydraulic fracturing produced water was examined to degrade dissolved organic carbon (DOC) and polyethylene glycols (PEGs). Biological treatment experiments of three produced water samples with DOC concentrations ranging from 22 to 420 mg/L and total dissolved solids (TDS) levels ranging from 26 to 157 g/L were conducted in 48-240 h batches. Samples were not pretreated to remove suspended solids and were inoculated with activated sludge and acclimated over several weeks. Results show that between 50% and 80% of DOC was removed in 12-24 h but a sizeable portion, on a mass basis, remained in the samples with higher DOC concentrations. PEGs were also shown to readily biodegrade into singly- and doubly-carboxylated metabolites, but were not shown to degrade past that point, leading to accumulation of PEG-dicarboxylates (PEG-diCs) in the batch reactors. Possible explanations include residence times that were too long, resulting in starved microbial populations (and thus, a stopping of PEG degradation) or the presence of other ethoxylated additives that degraded into PEGs and PEG-diCs and fed this accumulation. This work demonstrates that a well-acclimated microbial culture is capable of degrading a large portion of DOC in hydraulic fracturing wastewaters across a wide spectrum of TDS concentrations, indicating that biological treatment is a viable option for enabling reuse of produced water.


Net zero greenhouse emissions and energy recovery from food waste: manifestation from modelling a city-wide food waste management plan.
Food waste (FW) being a major solid waste component and of degradable nature is the most challenging to manage and mitigate greenhouse gas emissions (GHEs). Policymakers seek innovative approaches to achieve net zero objectives and recover resources from the FW which requires a comparative and holistic investigation of contemporary treatment methods. This study assessed the lifecycle of six alternative scenarios for reducing net GHEs and energy use potential from FW management in a metropolis, taking Hong Kong as a reference. In both impact categories, the business-as-usual (landfilling) was the worst-case scenario. The combined anaerobic digestion and composting (ADC) technique was ranked best in the global warming impact but was more energy intensive than anaerobic digestion with sludge landfilling (ADL). Incineration ranked second in net GHEs but less favourable for energy recovery from FW alone. The proposed integration of FW and biological wastewater treatment represented an enticing alternative. Integration by co-disposal and treatment with wastewater (CoDT-WW) performed above average in both categories, while anaerobic co-digestion with sewage sludge (AnCoD-SS) ranked fourth. The sensitivity analysis further identified critical parameters inherent to individual scenarios along with biogenic carbon emission and sequestration, revealing their significance on the magnitude of GHEs and scenarios' ranking. Capacity assessment of the studied treatment facilities showed a FW diversion potential of ∼60% while reducing the net GHEs by ∼70% compared to the base-case, indicating potential of net zero carbon emissions and energy footprint by increasing treatment capacity. From this study, policymakers can gain insights and guidelines for low-carbon urban infrastructure development worldwide.


GERD as a Complication of Laparoscopic Sleeve Gastrectomy for the Treatment of Obesity: A Systematic Review and Meta-Analysis.
The incidence of obesity is increasing in developed societies, and surgical treatment is one treatment option. The most common surgical treatment for obesity is laparoscopic sleeve gastrectomy (LSG). Gastroesophageal reflux disease (GERD) is a complication of both obesity and the surgical treatment of obesity. In this study, the PubMed database was searched using the keywords "GERD" and "bariatric surgery", and 987 papers published between 1 July 2017 and 30 June 2022 were retrieved. Nine papers met the inclusion criteria and were included in the meta-analysis. The articles were analyzed for the de novo occurrence of GERD after the treatment of its symptoms, the occurrence of erosive esophagitis, and Barrett's esophagus. In addition, interesting conclusions are presented from the papers that did not meet the inclusion criteria but shed light on the pathophysiology of GERD in obese patients undergoing LSG. In conclusion, the authors draw attention to the need for endoscopic surveillance in patients undergoing LSG, even in the absence of clinical signs of GERD.


Biomechanical evaluation of different reconstructive techniques of proximal tibia in revision total knee arthroplasty: An in-vitro and finite element analysis.
Bone loss and subsequent defects are often encountered in revision total knee arthroplasty. In particular, when the cortical rim of proximal tibia is breached, the surgical decision on the reconstructive options to be taken is challenging due to the variety of defects and the lack of data from clinical or experimental studies that can support it. The purpose of this study is to assess how different reconstructive techniques, when applied to an identical defect and bone condition, can be associated to dissimilar longevity of the revision procedure, and the role of a stem in this longevity. Proximal cortex strains and implant stability were measured in ten reconstructive techniques replicated with synthetic tibiae. The cancellous bone strains under each construct were assessed with finite element models which were validated against experimental strains. The measured strains and stability showed that the proximal cortex is not immune to the different reconstructive techniques when applied to an identical defect. The largest cancellous strain differences between modular and non-modular techniques indicate a distinct risk between reconstructive techniques, associated to the supporting capacity of cancellous bone at long term. The main finding of the present study is the observation that modular augments increases, on a long term basis, the potential risk of bone resorption relative to the non-modular techniques. In addition, the use of a press-fit stem in the scope of non-modular techniques can lead to improved stability and load transfer, which can contribute positively to the life expectancy of these techniques.


Why all placentas should be examined by a pathologist in 1990.
Placental pathology is rarely a part of the training for either obstetrician or pathologist. As a result there has been confusion regarding the potential benefits of routine placental examination. These benefits include clarification of the causes of many adverse pregnancy outcomes, improvement of the risk assessment for future pregnancies, and ascertainment of newborn risk for long-term neurodevelopment sequelae. Information on placental abnormalities may reveal the presence of chronic fetal insults and allow their differentiation from acute (peripartum) stresses. Current methods of risk assessment fail to identify the majority of pregnancies that end in prematurity, stillbirth, growth retardation, or fetal distress. We suggest that placental pathology should be a routine component of obstetric-neonatal care.


Brain MRI findings in neurologically symptomatic COVID-19 patients: a systematic review and meta-analysis.
Coronavirus disease 2019 (COVID-19) has been associated with nervous system involvement, with more than one-third of COVID-19 patients experiencing neurological manifestations. Utilizing a systematic review, this study aims to summarize brain MRI findings in COVID-19 patients presenting with neurological symptoms. Systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) checklist. The electronic databases of PubMed/MEDLINE, Embase, Scopus, and Web of Science were systematically searched for literature addressing brain MRI findings in COVID-19 patients with neurological symptoms. 25 publications containing a total number of 3118 COVID-19 patients with neurological symptoms who underwent MRI were included. The most common MRI findings and the respective pooled incidences in decreasing order were acute/subacute infarct (22%), olfactory bulb abnormalities (22%), white matter abnormalities (20%), cerebral microbleeds (17%), grey matter abnormalities (12%), leptomeningeal enhancement (10%), ADEM (Acute Disseminated Encephalomyelitis) or ADEM-like lesions (10%), non-traumatic ICH (10%), cranial neuropathy (8%), cortical gray matter signal changes compatible with encephalitis (8%), basal ganglia abnormalities (5%), PRES (Posterior Reversible Encephalopathy Syndrome) (3%), hypoxic-ischemic lesions (4%), venous thrombosis (2%), and cytotoxic lesions of the corpus callosum (2%). The present study revealed that a considerable proportion of patients with COVID-19 might harbor neurological abnormalities detectable by MRI. Among various findings, the most common MRI alterations are acute/subacute infarction, olfactory bulb abnormalities, white matter abnormalities, and cerebral microbleeds.


Dimethyl Fumarate Mitigates Tauopathy in Aβ-Induced Neuroblastoma SH-SY5Y Cells.
Alzheimer's disease pathogenesis is measured by two key hallmarks viz extracellular senile plaques composed of insoluble amyloid beta (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau, resulting in microtubule destabilization, synaptic damage and neurodegeneration. Accumulation of Aβ is an introducing pathological incident in Alzheimer's disease; hence, the effect of dimethyl fumarate (DMF) on Aβ1-42-induced alterations in phosphorylated tau, related protein kinases, fibrillogenesis and microtubule assembly in neuroblastoma SH-SY5Y cells was determined. DMF attenuated Aβ1-42-induced neuronal apoptosis by down-regulating protein levels of Bcl-2/Bax, cleaved caspase-3 and caspase-9. Aβ1-42-induced upsurge in tau phosphorylation at Ser396 and Thr231 epitopes was found to be declined by DMF pretreatment. The upregulated activity of glycogen synthase kinase-3 beta (GSK-3β) by Aβ1‑42 treatment was blocked by DMF pretreatment. PI3K substrate Akt (at Ser473) as well as Wnt dependent β-catenin and cyclin D1 activity was found to be upregulated by DMF pretreatment in Aβ1-42 treated cells. ThT fluorescence and MTT assay showed that DMF reduces Aβ fibrillogenesis and inhibit related cytotoxicity. Also, DMF exerts a protective effect on Aβ1-42-induced microtubule disassembly caused due to a reduction in polymerized β3-and α-tubulin. These results indicate that down-regulation of GSK-3β activity and subsequent activation of PI3K/Akt and Wnt/β-catenin signaling pathways are closely involved in the shielding effect of DMF against Aβ1-42-induced tau hyperphosphorylation. Modulating cellular events related to Aβ1-42-induced tau hyperphosphorylation, aggregation and microtubule stabilization offers new molecular insights into the defensive outcome of DMF towards appropriate management for Alzheimer's disease.


Acute coronavirus infection triggers a TNF-dependent osteoporotic phenotype in mice.
Millions of people died during the COVID-19 pandemic, but the vast majority of infected individuals survived. Now, some consequences of the disease, known as long COVID, are been revealed. Although the respiratory system is the target of Sars-CoV-2, COVID-19 can influence other parts of the body, including bone. The aim of this work was to investigate the impact of acute coronavirus infection in bone metabolism. We evaluated RANKL/OPG levels in serum samples of patients with and without acute COVID-19. In vitro, the effects of coronavirus in osteoclasts and osteoblasts were investigated. In vivo, we evaluated the bone phenotype in a BSL2 mouse model of SARS-like disease induced by murine coronavirus (MHV-3). Patients with acute COVID-19 presented decreased OPG and increased RANKL/OPG ratio in the serum versus healthy individuals. In vitro, MHV-3 infected macrophages and osteoclasts, increasing their differentiation and TNF release. Oppositely, osteoblasts were not infected. In vivo, MHV-3 lung infection triggered bone resorption in the femur of mice, increasing the number of osteoclasts at 3dpi and decreasing at 5dpi. Indeed, apoptotic-caspase-3+ cells have been detected in the femur after infection as well as viral RNA. RANKL/OPG ratio and TNF levels also increased in the femur after infection. Accordingly, the bone phenotype of TNFRp55-/- mice infected with MHV-3 showed no signs of bone resorption or increase in the number of osteoclasts. Coronavirus induces an osteoporotic phenotype in mice dependent on TNF and on macrophage/osteoclast infection.


The epidemiology of low vision and blindness associated with trichiasis in southern Sudan.
We investigated vision status associated with trachomatous trichiasis (TT) and explored age-sex patterns of low vision and blindness associated with trichiasis in Mankien district of southern Sudan where trachoma prevention and trichiasis surgery were absent. A population based survey was undertaken and eligible persons underwent eye examination. Visual acuity (VA) was tested using Snellen E chart and persons with TT identified. Vision status was defined using the WHO categories of visual impairment based on presenting VA: normal vision (VA > or = 6/18 in better eye); low vision (VA < 6/18 but > or = 3/60 in better eye); and blindness (VA < 3/60 in better eye). An ordinal logistic regression model was fitted and age/sex specific distribution of vision status predicted. Overall 341/3,567 persons examined had any TT. Analysis was based on 319 persons, 22 persons were excluded: 20 had both TT and cataract; and 2 had missing VA data. Of the 319 persons: 158(49.5%) had trichiasis-related corneal opacity (CO); bilateral TT and bilateral CO were found in 251(78.7%) and 110 (34.5%), respectively; 146 (45.8%) had low vision or blindness; the ratio of low vision to blindness was 3.2:1; and no sex differences were observed. In our model the predicted distribution of vision status was: normal vision, 53.9% (95% CI 50.9-56.9); low vision, 35.3% (95% CI 33.3-37.2); and blindness, 10.9% (95% CI 9.7-12.0). We have reported severe trichiasis and high prevalence of vision loss among persons with trichiasis. Our survey showed that almost 1 in 20 of the entire population suffered low vision or blindness associated with trachoma. The need for trichiasis surgery, trachoma prevention services, and rehabilitation of the blind is acute.


Enhanced cellular uptake and metabolic stability of lipo-oligoarginine peptides.
Developing efficient cellular delivery vectors is crucial for designing novel therapeutic agents to enhance their plasma membrane permeability and metabolic stability in cells. Previously, we engineered cell penetrating peptide vectors named as "lipo-oligoarginine peptides" (LOAPs) by conjugating a proper combination of fatty acid and oligoarginine that translocated into cell easily without adverse effect on cell viability. In the present study, we report a systemic evaluation of cellular uptake and metabolic stability of LOAPs in Jurkat cells by introducing different combination of D-Arg residues in the peptide backbone. The cellular uptake and intracellular fate, cell viability, and metabolic stability and proteolytic degradation patterns of various LOAPs consisted of different combination of L- and D-Arg sequences were confirmed by flow cytometry, cytotoxicity assay, and analytical RP-HPLC with MALDI-TOF mass. All investigated LOAPs penetrated the cell efficiently with low cellular toxicity. The LOAPs having D-Arg residues at their N-termini seemed to have better metabolic stability than the LOAPs having C-terminal D-Arg residues. The metabolic degradation patterns were similar among all investigated LOAPs. The major hydrolytic site was between lauroyl group and β-Ala residue. Without the lipid chain, the oligoarginine peptide was pumped out ofcells easily. The results presented in this study suggest that structurally modified LOAPs could be used as a novel CPP design toward improved therapeutic application.


Association between metabolic control and oral health in children with type 1 diabetes mellitus.
Type 1 diabetes mellitus is the most common chronic disease and can be reflected in the oral cavity. The aim of this study was to analyze the impact of metabolic control on saliva, dental caries, dental plaque, gingival inflammation, and cariogenic bacteria in saliva. A case-control epidemiologic study was performed on children with type 1 diabetes (ages 10-15 years) separated into two groups: 34 children with good metabolic control of glycated hemoglobin (HbA1c < 7.5%) and 46 children with poor metabolic control of glycated hemoglobin (HbA1c > 7.5%). Oral status was assessed using the Decay, Missing, and Filled Teeth index for permanent teeth (DMFT), plaque index and gingival index. The stimulated salivary flow rate was measured, and the colonies of Streptococcus mutans and Lactobacillus in saliva were determined. The observed children answered questions related to their frequency of brushing habits, dental visits and parents' education. Mann-Whitney U Test, Chi-Square test and Fisher's exact test were used in the statistical analyses. The significance level was set at p < 0.05. The children with diabetes with poor metabolic control had significantly higher values of the DMFT index, plaque index, and gingival index, more colonies, and a higher risk of Streptococcus mutans and Lactobacillus than the children with diabetes with good metabolic control (p < 0.001). The level of metabolic control of diabetes had no influence on salivary flow rates (p > 0.05). The majority of both groups with good and poor metabolic control brushed their teeth once per day, and they visited the dentist only when necessary (61.3%). However, the parents of children in both groups had medium to low levels of education, without any significant difference between groups (p > 0.05). The results indicate that children with diabetes have a lower level of oral hygiene and are potentially to dental caries and periodontal diseases, mainly when their metabolic disorder is uncontrolled.


Growth of Mycobacterium leprae in a redox system: III. Evidence of growth at low temperature (psychrophilia) and, further refinement of growth medium.
Considerable growth enhancement, largely as non-acid fast, slender and long rods has been seen when incubated at 10 degrees C. Concentration of some of the media constituents have been reduced that has improved the quantum of growth. A remarkable proneness to physical disintegration of the grown bacilli has been seen and its significance discussed. Also, the possible immunogenic advantage of non-AF M. leprae has been discussed. The question of identification is still not solved, and work is in progress.


Medulloblastoma epigenetics and the path to clinical innovation.
In the last decade, a number of genomic and pharmacological studies have demonstrated the importance of epigenetic dysregulation in medulloblastoma initiation and progression. High throughput approaches including gene expression array, next-generation sequencing (NGS), and methylation profiling have now clearly identified at least four molecular subgroups within medulloblastoma, each with distinct clinical and prognostic characteristics. These studies have clearly shown that despite the overall paucity of mutations, clinically relevant events do occur within the cellular epigenetic machinery. Thus, this review aims to provide an overview of our current understanding of the spectrum of epi-oncogenetic perturbations in medulloblastoma. Comprehensive review of epigenetic profiles of different subgroups of medulloblastoma in the context of molecular features. Epigenetic regulation is mediated mainly by DNA methylation, histone modifications and microRNAs (miRNA). Importantly, epigenetic mis-events are reversible and have immense therapeutic potential. The widespread epigenetic alterations present in these tumors has generated intense interest in their use as therapeutic targets. We provide an assessment of the progress that has been made towards the development of molecular subtypes-targeted therapies and the current status of clinical trials that have leveraged these recent advances.


Children with autism display altered ankle strategies when changing speed during over-ground gait.
Examining gait mechanics when altering speed has been used in various clinical populations to understand the pervasiveness of neurological impairments. Few studies have examined whether different gait mechanics exist when altering speed in children with Autism Spectrum Disorder, although autism may present as a movement disorder due to abnormalities in the central nervous system. Most autism gait-related research has used preferred walking speed, while different speeds may yield discernible patterns that can be used for future interventions. The purpose of this study was to examine kinematic strategies used by children with autism in preferred, fast, and slow walking speeds. Three-dimensional kinematic data were obtained on 14 children (aged 8-17 years) during preferred, fast, and slow walking. Hip, knee, and ankle angular joint positions were examined at loading response, pre-swing, and terminal swing sub-phases due to their importance on forward propulsion and weight transfer. Repeated measures analyses of variance (α = 0.05) were used to test for statistical differences and effect sizes were interpreted with Cohen's d. Although significant differences were observed for each joint and sub-phase, the left and right ankle joints during pre-swing displayed the most consistent differences among conditions (p < 0.001, and p < 0.001), respectively. Additionally, the left ankle displayed a moderate effect size (η2 = 0.71) and the right ankle displayed a large effect size (η2 = 0.80). These findings reveal that the ankle joint, during pre-swing, is the primary kinematic strategy used by children with autism when altering gait speed, whereas previous evidence suggests that the hip joint was the primary strategy.


The disciplines of engineering and history: some common ground.
The nature of engineering and history as disciplines are explored and found to have some striking similarities, for example in the importance they place on context and practitioner involvement. They are found to be different from science, which focuses more on universal generalizations rather than on the particulars of given situations. The history of technology is paid special attention, because the discipline has developed in a way that incorporates both scientific (generalizing) and historical (context specific) characteristics. Proposals are made for giving historical studies greater space in engineering education.


Epigenetic profiling of gallbladder cancer and gall stone diseases: Evaluation of role of tumour associated genes.
As on today, the global mortality rate of gallbladder cancer is still very high. Both genetic and epigenetic alterations play pivotal roles in the development of cancer. We selected seven tumour associated genes, implicated in other cancers, to assess their methylation status in gallbladder cancer and gallstone diseases. To study the promoter methylation of certain tumour associated genes in the molecular pathogenesis of gallbladder cancer and gall stone diseases. Methylation specific PCR for seven tumour associated genes, viz., MASPIN, 14-3-3 sigma gene, THBS1, FLNC, HLTF, COX-2 and SOCS1, was performed in 50 gallbladder cancer (GBC), 30 gall stone diseases (GSD) and their respective adjacent control tissues. Semi-quantitative PCR and immunohistochemistry was carried out to check the expression level. Student's t-test was carried out to compare the differences in the methylation and expression patterns between cases and control tissues. We observed methylation of CpG islands in seven of the studied markers, but, the frequency of methylation was found varying among different samples. Of them, 14-33 sigma showed methylation in 45 GBC (90%; p=0.0001) and 25 GSD (86.66%; p=0.001), MASPIN in 35 GBC (70%; p=0.0008) and 18 GSD (51.43%; p=0.040), FLNC in 16 GBC (32%; p=0.0044) and 9 GSD (25.71%; p=ns), THBS1 in 26 GBC (52%; p=0.0009) and 10 GSD (28.57%; p=0.0505), HLTF in 8 GBC (16%; p=ns) and 2 GSD (5.71%; p=ns), COX2 in 10 GBC (20%; p=ns) and 6 GSD (17.14%; p=ns) and SOCS-1 in 3 GBC samples only (6%; p=ns), but not in GSD. Semi-quantitative PCR revealed down regulation in MASPIN, 14-3-3 sigma, THBS1, HLTF, COX2 and SOCS1 in advanced gallbladder cases. Immunohistochemistry further confirmed the down-regulation of SOCS1 in GBC. The present study infers that accumulation of epigenetic alterations increases poor prognosis of GBC patients. Out of seven genes, MASPIN and THBS1 play key epigenetic role in GBC, but not in GSD. The reason for downregulation of SOCS1 only in GBC, and unaltered expression of 14-3-3 sigma protein in all the GBC and GSD tissue samples is not clear. Further investigation on the expression pattern of these genes in GBC cell lines may elucidate their likely functional role in in association with gallbladder cancer.


The use of the G1 and Octosmart programs in detecting temporal changes in the visual field.
The Octopus program Octosmart is able to classify visual fields into six classes. In the program a horizontal bar indicates these classes, and an indicator points to the most probable position, related to the measured pathology. The width of this dashed indicator shows the range of possible fluctuations in the measurement and, therefore, its precision. This study sets out to analyse the suitability of this display mode using other visual-field index data. The visual fields of 83 glaucomatous eyes of 61 patients of various etiological groups and glaucoma suspects were studied for periods varying from 1 to 5 years in a retrospective study. All examinations were performed with the G1 Octopus program and analyzed with the Octosmart program. The statistical significance of linear trends of the visual-field indices, mean defect (MD) and corrected loss variance (CLV), and the class shown by the indicator (POI = position of indicator) were determined, and their regression coefficients were analyzed by means of a linear trend test as a function of time. Of the sample of 83 tested eyes, a total of 18 significant trends were recorded after five examinations. All visual-field indices showed a trend towards amelioration. The 18 significant trends observed must be attributed to perturbing long-term fluctuations and, despite their statistical significance, are of little clinical value. It is questionable whether an increased number of examinations per eye would have attenuated the threshold fluctuations sufficiently to make the change in field class more reliable.


Urinary biopyrrins: potential biomarker for monitoring of the response to treatment with anxiolytics.
During periods of psychological stress, excess amounts of free radicals are produced. Bilirubin oxidative metabolites (biopyrrins; BOM) are generated from bilirubin as a result of its scavenging action against free radicals. We investigated whether the urinary excretion of biopyrrins is altered by anxiolytics. In the present study, mice were immobilized for a period of 6 hr. Alprazolam (0.1-1 mg/kg of body-weight) was administered 30 min. before subjecting the animals to acute stress. The BOM concentrations in urine and the corticosterone levels in serum were measured by ELISA with an anti-bilirubin antibody and EIA, respectively. We observed an increase in urinary biopyrrins in stressed mice in comparison with non-stressed mice and a decrease after the treatment of stressed animals with alprazolam. A correlation between urinary BOM and serum corticosterone levels was found. Urinary levels of biopyrrins might be used to assess the response to anxiolytics prescribed during acute stress periods.


HABP1/p32/gC1qR induces aberrant growth and morphology in Schizosaccharomyces pombe through its N-terminal alpha helix.
Hyaluronan binding protein (HABP1), located on human chromosome 17p13.3, was identified and characterized as being involved in cellular signaling from our laboratory. Here, we demonstrate that HABP1 expression in Schizosaccharomyces pombe induces growth inhibition, morphological abnormalities like elongation, multinucleation and aberrant cell septum formation in several strains of S. pombe, implicating its role in cell cycle progression and cytokinesis. This argument is further strengthened by an observed delay in the maximal expression of cell cycle regulatory proteins like CDC 2 and CDC 25 coupled to the direct interaction of HABP1 with CDC 25. In order to pinpoint the interacting domain of HABP1, its N- and C-terminal truncated variants (DeltaN.HABP1 and DeltaC.HABP1, respectively) were utilized which revealed that while expression of the former did not alter the phenotype, the latter generated morphological changes similar to those imparted upon HABP1 expression. It was also noted that along with HABP1, DeltaC.HABP1 too directly interacts with CDC 25 while DeltaN.HABP1 does not. Taken together, these data suggest that HABP1 induces morphological changes and modulates the cell cycle by interacting with proteins like CDC 25 through its N-terminal alpha-helix.


Observations on the gastric epithelium of ascidians with special reference to Styela clava.
Transmission electron microscopy shows the gastric epithelium of Styela clava to comprise at least three distinct cell types. Ciliated mucous cells which form the crest of each stomach ridge produce mucus by an unexpected route. Vacuolated cells lining the ridge sides appear to be absorptive in function. Gastric enzymes are produced by typical protein secreting cells scattered amongst the vacuolated cells. Undifferentiated cells are found in the crypts between ridges. The structure and function of the gastric epithelium in Styela is discussed with special reference to the wider concepts of ascidian gut organization.


Evaluation of a biochemical method for measuring platelet life-span.
Acetylsalicylic Acid (Aspirin) inhibits the formation of Malonaldehyde, a degradation product of the proaggregating Prostaglandins, during the life-span platelets in the circulating blood. After ingestion of 1.5 g of aspirin, there is a blockage of the formation of Malonaldehyde, followed by a progressive return to normal values, after an average of 8 days, in a healthy person. This fact is applied to the determination of half-life, found to be 3.7 +/- 1.3 days; a value in accord with those found by the isotopic method using 51Cr. The reproductibility of this method indicates a clinical application.


Suicide following the death of a sibling: a nationwide follow-up study from Sweden.
The death of a sibling can trigger grief and depression. Sibling deaths from external causes may be particularly detrimental, since they are often sudden. We aimed to examine the association between the death of an adult sibling from external causes and the risk of suicide among surviving siblings up to 18 years after bereavement. We adjusted for intrafamily correlation in death risks, which might occur because of shared genetics and shared early-life experiences of siblings in the same family. A follow-up study between 1981 and 2002 based on the total population. Sweden. Swedes aged 25-64 years (n=1 748 069). Suicide from the Swedish cause of death register. An increased risk of mortality from suicide was found among persons who had experienced the death of a sibling. In women, the suicide risk was 1.55 times that of non-bereaved persons (95% CI 0.99 to 2.44), and in men it was 1.28 times higher (95% CI 0.93 to 1.77). If one sibling committed suicide, the risk of the remaining sibling also committing suicide was 3.19 (95% CI 1.23 to 8.25) among women and 2.44 (95% CI 1.34 to 4.45) among men. Associations with other main causes of death-such as external other than suicide, cardiovascular diseases or cancer-were generally much smaller and statistically not significant in either sex. We found no clear support for a specific time pattern according to time since a sibling's death. Our study provided evidence for suicide risk associated with the death of a sibling at adult age, revealing that bereaved persons' risk of suicide is higher when siblings die from suicide, even when adjusting for intrafamily correlation in death risks.


Patterns of neurogenic bladder dysfunction in sacral agenesis.
Patterns of neurogenic bladder disease were defined in 13 patients with sacral agenesis. Each patient demonstrated an individualized mixture of upper and/or lower motor neuronal deficits. The paucity of clinical parameters capable of identifying and assessing bladder dysfunction in these patients mandates complete neurourological evaluation and careful followup.


Isoproterenol increases Na+-K+-ATPase activity by membrane insertion of alpha-subunits in lung alveolar cells.
Catecholamines promote lung edema clearance via beta-adrenergic-mediated stimulation of active Na+ transport across the alveolar epithelium. Because alveolar epithelial type II cell Na+-K+-ATPase contributes to vectorial Na+ flux, the present study was designed to investigate whether Na+-K+-ATPase undergoes acute changes in its catalytic activity in response to beta-adrenergic-receptor stimulation. Na+-K+-ATPase activity increased threefold in cells incubated with 1 microM isoproterenol for 15 min, which also resulted in a fourfold increase in the cellular levels of cAMP. Forskolin (10 microM) also stimulated Na+-K+-ATPase activity as well as ouabain binding. The increase in Na+-K+-ATPase activity was abolished when cells were coincubated with a cAMP-dependent protein kinase inhibitor. This stimulation, however, was not due to protein kinase-dependent phosphorylation of the Na+-K+-ATPase alpha-subunit; rather, it was the result of an increased number of alpha-subunits recruited from the late endosomes into the plasma membrane. The recruitment of alpha-subunits to the plasma membrane was prevented by stabilizing the cortical actin cytoskeleton with phallacidin or by blocking anterograde transport with brefeldin A but was unaffected by coincubation with amiloride. In conclusion, isoproterenol increases Na+-K+-ATPase activity in alveolar type II epithelial cells by recruiting alpha-subunits into the plasma membrane from an intracellular compartment in an Na+-independent manner.


The benefits of excellence. A cost-effective treatment programme for pressure sores.
This paper evaluates a policy for treating patients with established pressure sores. The results show that excellent nursing care has a significant effect on the rate of healing.


Comparison of alpha-ketoisocaproic acid and glucose in rats: effects on insulin and somatostatin release and on islet cAMP content.
The insulinotropic effects of alpha-ketoisocaproic acid and glucose reveal many common characteristics in vivo and in vitro. They qualify as initiators of insulin release, their action is amplified by potentiators of insulin release, and they have a similar potency at equimolar concentrations. The dynamics of insulin release evoked by alpha-ketoisocaproic acid and glucose are similar. Epinephrine completely inhibits the insulinotropic effect of glucose and alpha-ketoisocaproic acid. Mannoheptulose exhibits a complete, immediate and reversible blockade of glucose-induced insulin release. In contrast, inhibition of alpha-ketoisocaproic acid-induced insulin release occurs after a lag period and is not reversed by removal of the inhibitor. alpha-ketoisocaproic acid, at equimolar concentrations, is several-fold more effective than glucose in elevating cAMP content in islet. alpha ketoisocaproic acid and glucose are about equally effective in stimulating somatostatin release from isolated rat pancreatic islets. This stimulation is inhibited by epinephrine. Mannoheptulose inhibits only somatostatin release induced by glucose but not by alpha-ketoisocaproic acid. It suggested that the insulinotropic characteristics of glucose and alpha-ketoisocaproic acid reveal many common features, while their mode of action appears to be different.


The impact of stage and treatment modality on the likelihood of second malignancies and hematopoietic disorders in Hodgkin's disease.
Two hundred patients treated with curative intent for Hodgkin's disease between October 1964 and April 1984 at a single institution were studied retrospectively for development of second malignancies. The minimum follow-up was 2 years (median, 11 years). The staging distribution was IA-B, 61; IIA, 54; IIB, 20; IIIA, 46; and IIIB, 19. Sixty-one percent of the patients had laparotomy. Initial management was irradiation alone (RA) in 143 patients and a combination of chemotherapy and irradiation (CB) in 57 patients. Actuarial 10-year survival rates were 82%, IA-B; 78%, IIA; 66%, IIB; 66%, IIIA; and 24%, IIIB. Cause-specific deaths due to Hodgkin's disease or complications of initial or salvage therapy occurred in 3% of IA-B patients, 18% of IIA-B patients, and 35% of IIIA-B patients. One patient had a prior T3N1 squamous cell carcinoma of the retromolar trigone, and a second was diagnosed with concurrent Hodgkin's disease and granulocytic sarcoma. Subsequent solid tumors have occurred in six patients from 5 to 21 years after treatment, including papillary carcinoma of the thyroid, renal cell carcinoma, unilateral breast carcinoma, cervix carcinoma in situ, and lung carcinoma after RA, and bilateral breast carcinoma after CB. Seven fatal hematopoietic disorders (HPDs) were observed, including four acute leukemias, one dysmyeloproliferative syndrome (DMPS), one autoimmune hemolytic anemia, and one aplastic anemia. Two occurred in patients initially managed with RA who subsequently required chemotherapy for relapse. Five HPDs occurred in patients initially managed with CB who never relapsed. All HPDs were observed between 2 and 7.5 years after administration of chemotherapy. Statistical analysis of the data using a rerandomization test on Gehan ranks of treatment and clinical variables showed significant correlations between development of a secondary HPD and (1) initial management with CB; (2) higher doses of chemotherapy; and (3) more advanced disease, particularly IIIB. When only the five events generally associated with treatment (i.e. the four leukemias and one DMPS) were considered, there was a significant correlation with exposure to chemotherapy and presentation with advanced disease. The patient population was small so that interdependence between treatment factors and initial extent of disease in affecting the risk of a secondary HPD cannot be discounted but should be further investigated with larger patient populations.


The Role of Step Therapy in the Treatment of Migraine.
This review examines recent evidence and applies bioethical principles to evaluate the benefits and risks of using step therapy in the treatment of migraine. With the CGRP mAbs, gepants, and lasmiditan now on the market for up to 5 years, new research, including network meta-analyses and long-term use studies, can evaluate the comparative efficacy, tolerability, and adherence of these medications relative to older acute and preventive medications for the treatment of migraine. Deciding how medications are chosen for patients requires accounting for many factors including sustainability, efficacy, tolerability, and preference. Newer research can help give clarity on the appropriateness of gating certain treatment options behind others.


A review of anti-tumour effects of Ganoderma lucidum in gastrointestinal cancer.
Gastrointestinal (GI) cancer is the most common cancer in the world and one of the main causes of cancer-related death. Clinically, surgical excision and chemotherapy are the main treatment methods for GI cancer, which is unfortunately accompanied with serious adverse reactions and drug toxicity, bringing irreversible damage to patients and seriously affecting the quality of life. Ganoderma lucidum (G. lucidum) has a long history of medicinal and edible use in China. Its bioactive compounds mainly include polysaccharides, triterpenes, and proteins, which have potential anti-tumor activities by inhibiting proliferation, inducing apoptosis, inhibiting metastasis, and regulating autophagy. Currently, there is no in-depth review on the anti-tumor effect of G. lucidum in GI cancer. Therefore, this review is an attempt to compile the basic characteristics, anti-GI caner mechanisms, and clinical application of G. lucidum, aiming to provide a reference for further research on the role of G. lucidum in the prevention and treatment of GI cancer from the perspective of traditional Chinese and western medicine.


The hippocampus: functional and structural correlations.
This paper reviews the current literature relating neuropsychological measures of the functional integrity of the hippocampus with structural indices obtained from magnetic resonance imaging (MRI) volumetric scans and the histological analysis of postoperative specimens. The first part of the discussion presents an overview of the current methods and applications of volumetric MRI of the hippocampus. The processes and contemporary standards applied to the histological analysis of resected hippocampal tissue are also described. Both of these measures of structural integrity have been studied in relation to preoperative performance on neuropsychological tests, including the intracarotid sodium amytal test, and postoperative memory functioning. The findings from these studies are reviewed. The challenges presented by these new technologies to the field of neuropsychology are discussed.


Impact of surgery and chemotherapy timing on outcomes in older versus younger epithelial ovarian cancer patients: A nationwide Danish cohort study.
To explore differences in surgical complexity, chemotherapy administration, and treatment delays between younger and older Danish patients with epithelial ovarian cancer (EOC). We included a nationwide cohort diagnosed with EOC from 2013 to 2018. We described surgical complexity and outcomes, the extent of chemotherapy and treatment delays stratified by age (<70 and ≥ 70 years), and surgical modality (primary, interval, or no debulking surgery). In total, we included 2946 patients. For patients with advanced-stage disease, 52% of the older patients versus 25% of the younger patients did not undergo primary debulking surgery (PDS) or interval debulking surgery (IDS). For patients undergoing PDS or IDS, older patients underwent less extensive surgery and more often had residual disease after surgery >0 cm compared to younger patients. Furthermore, older patients were less often treated with chemotherapy. Older patients had PDS later than younger. We did not find any differences between age groups concerning treatment delays. Two-year cancer-specific survival differed significantly between age groups regardless of curatively intended treatment. This study demonstrates that older patients are treated less actively concerning surgical and oncological treatment than younger patients, leading to worse cancer-specific survival. Older patients do not experience more treatment delays than younger ones.


Variables influencing executive functioning in preschool hearing-impaired children implanted within 24 months of age: an observational cohort study.
Executive Functions (EFs) are fundamental to every aspect of life. The present study was implemented to evaluate factors influencing their development in a group of preschools orally educated profoundly deaf children of hearing parents, who received CI within 2 years of age. Twenty-five preschool CI children were tested using the Battery for Assessment of Executive Functions (BAFE) to assess their flexibility, inhibition, and non-verbal visuo-spatial working memory skills. The percentage of children performing in normal range was reported for each of the EF subtests. Mann-Whitney and Kruskal-Wallis were performed to assess differences between gender, listening mode, and degree of parents' education subgroups. The Spearman Rank Correlation Coefficient was calculated to investigate the relationship between EF scores of audiological and linguistic variables. Percentages ranging from 76 to 92% of the children reached adequate EF scores at BAFE. Significant relations (p < 0.05) were found between EFs and early intervention, listening, and linguistic skills. Furthermore, CI children from families with higher education level performed better at the response shifting, inhibitory control, and attention flexibility tasks. Economic income correlated significantly with flexibility and inhibitory skills. Females performed better than males only in the attention flexibility task. The present study is one of the first to focus attention on the development of EFs in preschool CI children, providing an initial understanding of the characteristics of EFs at the age when these skills emerge. Clinical practice must pay increasing attention to these aspects which are becoming the new emerging challenge of rehabilitation programs.


Chest tube thoracostomy: A simple life-saving procedure with potential hazardous risks.
Chest tube thoracostomy is a simple life-saving procedure with many benefits but comes with significant potential morbidity. Potentially all intra-thoracic organs are at risk of possible injury as well as peritoneal. We present four patients who had chest tube thoracostomy with potential complications fortunately were managed promptly and recovered fully. Complications related to tube thoracostomy is reported up to 25 % especially when done under emergency conditions. While the procedure is reported safe, it's associated morbidity is not well described. Additionally, clinicians are urged to follow standard operating procedures and address the potential complications with consent to their patients. Chest tube thoracostomy is an invasive life-saving procedure performed across various clinical ranks and sub-specialties. It has potential life-threatening risks and complications therefore clinicians should be well trained to identify such complications and address accordingly.


Thermodynamic properties of molecular borane amines and the [BH4-][NH4+] salt for chemical hydrogen storage systems from ab initio electronic structure theory.
The heats of formation for the borane amines BH3NH3, BH2NH2, and HBNH, tetrahedral BH4-, and the BN molecule have been calculated by using ab initio molecular orbital theory. Coupled cluster calculations with single and double excitations and perturbative triples (CCSD(T)) were employed for the total valence electronic energies. Correlation consistent basis sets were used, up through the augmented quadruple-zeta, to extrapolate to the complete basis set limit. Core/valence, scalar relativistic, and spin-orbit corrections were included in an additive fashion to predict the atomization energies. Geometries were calculated at the CCSD(T) level up through at least aug-cc-pVTZ and frequencies were calculated at the CCSD(T)/aug-cc-pVDZ level. The heats of formation (in kcal/mol) at 0 K in the gas phase are Delta Hf(BH3NH3) = -9.1, Delta Hf(BH2NH2) = -15.9, Delta Hf(BHNH) = 13.6, Delta Hf(BN) = 146.4, and Delta Hf(BH4-) = -11.6. The reported experimental value for Delta Hf(BN) is clearly in error. The heat of formation of the salt [BH4-][NH4+](s) has been estimated by using an empirical expression for the lattice energy and the calculated heats of formation of the two component ions. The calculations show that both BH3NH3(g) and [BH4-][NH4+](s) can serve as good hydrogen storage systems which release H2 in a slightly exothermic process. The hydride affinity of BH3 is calculated to be 72.2 kcal/mol, in excellent agreement with the experimental value at 298 K of 74.2 +/- 2.8 kcal/mol.


Computerized texture analysis of mammographic parenchymal patterns of digitized mammograms.
Mammographic density and parenchymal patterns have been shown to be related to the risk of developing breast cancer. Thus, computerized texture analysis of breast parenchymal patterns on mammograms may be useful in assessing breast cancer risk. A comparative evaluation was conducted of various computer-extracted texture features of mammographic parenchymal patterns of women with BRCA1/BRCA2 gene mutations and those of women at low risk of developing breast cancer. Mammograms from 172 subjects (30 women with either the BRCA1 or BRCA2 gene mutation and 142 low-risk women) were analyzed. Computerized texture features were extracted from regions-of-interest to assess the mammographic parenchymal patterns in the images. Receiver operating characteristic analysis was used to assess the performance of these features in the task of distinguishing between the two groups of women. Quantitative texture analysis on digitized mammograms demonstrated that gene-mutation carriers and low-risk women have different mammographic parenchymal patterns. Gene-mutation carriers presented with parenchymal patterns that were denser, coarser, and lower in contrast than those of the low-risk group. For the gene-mutation carriers, their mammographic patterns appear to contain less high-frequency component as indicated by higher coarseness values, lower fractal dimensions, and smaller edge gradients, which yielded corresponding A(z) values of 0.79, 0.84, and 0.78, respectively, in the task of distinguishing between gene-mutation carriers and the low-risk group with the entire dataset. The contrast measure calculated from co-occurrence matrix method, which describes local image variation, yielded an A(z) value of 0.86 in distinguishing between the two groups of women. Computerized texture analysis of mammograms provides radiographic descriptors of mammographic parenchymal patterns. The computer-extracted features may be useful for identifying women at high risk for breast cancer and for monitoring the treatment of breast cancer patients.


A two-dose dexamethasone suppression test in patients with psychiatric illness.
After exposure to a low and high dose dexamethasone regime, 11 of 34 acute psychiatric inpatients demonstrated abnormal dexamethasone suppression characterized by morning and/or mid-afternoon escape from suppression. This abnormality of suppression was found in primary depression, in mania, and in acute schizophrenia. In primary depression, the presence of abnormal dexamethasone suppression failed to discriminate "endogenous" depressed from "other depressed" subjects. Because nonsuppression to a high dose of dexamethasone is also found in patients with ectopic ACTH secretion and in patients with autonomous adrenal tumors, caution is necessary in the interpretation of nonsuppression which persists after recovery from psychiatric illness. As patients with Cushing's syndrome of uncertain etiology may be referred to a psychiatrist for a diagnostic evaluation, the psychological correlates of abnormal dexamethasone suppression need to be established with greater certainty.


Actual situation in Fusarium taxonomy.
The importance of choosing the proper systematic system in Fusarium taxonomy is stated and a comparative listing of synonyms of the sections Sporotrichiella, Roseum, Liseola, Discolor, Gibbosum, Martiella, as used by various authors in three monographs, is given (2, 4, 9).


Non-Invasive Diagnostic Test for Advanced Fibrosis in Adolescents With Non-Alcoholic Fatty Liver Disease.
Non-alcoholic fatty liver disease (NAFLD) is a multifaceted disease that includes a wide spectrum of liver damage. The presence and the degree of fibrosis are considered important factors for the prognosis of NAFLD and in predicting the risk of developing cirrhosis. Our aim was to evaluate the usefulness of four fibrosis scores (aspartate aminotransferase/Platelet Index [APRI], FIB-4, NAFLD Fibrosis Score [NFS], and Hepamet) in predicting different degrees of fibrosis among children with biopsy-proven NAFLD. About 286 adolescents [mean age 14.3 years ± 2.5; 154 (53.6%) males], referred between January 2014 and December 2019, with biopsy-proven NAFLD were enrolled. About 173 (60.4%) patients presented fibrosis at histological analysis. In particular: 140 (49.3%) patients had F = 1, 31 (10.8%), had F = 2 and 2 (0.66%) had F = 3. APRI (AUROC 0.619, 95% CI 0.556-0.679) and Hepamet (AUROC 0.778, 95% CI 0.722-0.828) scores had significant (p < 0.001) accuracy to distinguish subjects with fibrosis; while NFS and FIB-4 had not. APRI had a positive predictive value (PPV) of 62.77% (95% CI 57.96-67.35) and an negative predictive value (NPV) of 52.01% (95% CI 46.54-57.43); Hepamet a PPV of 63.24% (95% CI 59.95-66.41) and an NPV of 61.29% (52.9-69.01). Our study showed that Hepamet and APRI perform better than NFS and FIB-4 for identifying fibrosis in patients with NAFLD, but do not have PPVs so high to be considered diagnostic. Therefore, they cannot be employed, in children, for a certain diagnosis of fibrosis or its progression and cannot replace liver biopsy as the gold diagnostic standard. It is, therefore, necessary to continue to research and develop new markers of exclusive fibrosis.


Amadeus microkeratome: experience with the first 2000 cases and lessons learned.
To assess the safety and efficacy of the Amadeus microkeratome and to report on lessons learnt in optimizing results from its use. A retrospective review of the flap-related complications of 2000 laser in situ keratomileusis (LASIK) procedures performed by one surgeon using the Amadeus microkeratome (AMO, Irvine, CA, USA) was conducted. One hundred consecutive cases had preoperative and intraoperative pachymetry to evaluate the relationship between flap thickness, corneal thickness and reuse of the blade. There were 35 cases of minor epithelial defects (1.8%) and four eyes with major epithelial defects (0.2%). There were no cases of suction loss, buttonholes, or incomplete or damaged flaps. There were four free caps (0.2%). Twenty-five cases had minor wrinkles and two cases had significant folds requiring relifts. Thinner corneas resulted in thinner flaps (P < 0.0001). Reuse of the blade resulted in thinner flaps (P = 0.0001). The Amadeus is a safe and reliable microkeratome. Although short, there is a learning curve with use of the instrument. Corneal thickness and reuse of the blade affect flap thickness.


Effects of light and nutrient availability on dry matter and N allocation in six successional grassland species : Testing for resource ratio effects.
Recent discussions on determinants of competitive success during succession require the study of the combined effect of light and nutrient availability on growth and allocation. These effects can be used to predict the outcome of competition at changing resource availabilities. This work is part of a study on the successional sequence in permanent grassland starting after fertilizer application is stopped, but with continued mowing, in order to restore former species-rich communities. This yields a successional sequence which proceeds from grasslands with a high nutrient availability and a closed canopy, to grasslands with a low nutrient availability and an open canopy. If allocation is related to competitive ability, species from the productive stages would be expected to allocate more biomass and nitrogen to leaves, which could make them better competitors for light, while species from the unproductive stages would allocate more biomass to roots, which could make them better nutrient competitors. This study reports on growth, specific leaf area (SLA), vertical display of leaves, and allocation of biomass and nitrogen of six grassland species from this successional sequence at 16 combinations of light and nutrient supply. Species from the poorer successional stages reached a lower final dry weight than species from the richer stages, over all treatment combinations. The experimental design made it possible to test for unique effects of the resource ratio effect of light and nutrients on allocation characteristics. This resource-ratio effect was defined as the ratio light intensity/(light intensity + nutrient supply rate), using standardized levels for the treatments. The within-species variation (plasticity) in both allocation of dry matter and nitrogen was linearly related to this resource-ratio effect. Some interspecific differences in this relationship were found which could be related to the position of the species along the successional gradient. However, the range of plasticity in allocation pattern expressed within each species was much larger than the differences between species. It was concluded that allocation differences between these grassland species are relatively unimportant, given the large amount of plasticity in these traits. Interspecific differences in SLA and vertical stature seemed to be more important in explaining the position of species along the successional gradient.


Hydrostatic pressure drives microbe-mediated biodegradation of microplastics in surface sediments of deep reservoirs: Novel findings from hydrostatic pressure simulation experiments.
Microplastics originate from the physical, chemical, or biological degradation of plastics in the environment. Once ingested by organisms at the bottom of the food chain, microplastics are passed on to organisms at higher trophic levels, posing a threat to human health. The distribution of microplastics and the metabolic pathways involved in their microbial degradation in surface sediments of drinking water reservoirs are still poorly understood. This study analyzed the occurrence patterns of microplastics and microbial community structure associated with microplastic biodegradation in surface sediments from a deep reservoir at various hydrostatic pressures. Based on the results of Fourier-transform and laser direct infrared spectroscopy, elevating the pressure resulted in altered sizes and shapes of microplastics in sediment samples with the presence of microorganisms. The influence of hydrostatic pressure on small-sized microplastics (20-500 μm) was pronounced. For instance, high pressure accelerated the breakdown of fibers, pellets, and fragments into smaller-sized microplastics. In particular, the mean size of polyethylene terephthalate microplastics decreased from 425.78 μm at atmospheric pressure to 366.62 μm at 0.7 Mpa. Metagenomic analysis revealed an increase in the relative abundances of plastic-degrading genera, such as Rhodococcus, Flavobacterium, and Aspergillus, in response to elevated pressures. Eight functional genes for biodegradation of polystyrene, polyethylene, and polyethylene terephthalate microplastics were annotated, including paaK, ladA, tphA3. Of these, tphA3 gene abundance was negatively influenced by hydrostatic pressure, providing direct evidence for the pathway by which microbial metabolism of polyethylene terephthalate led to decreased microplastic size under high pressure conditions. This study presents novel insights into hydrostatic pressure-driven microbial community structure, functional gene abundance, and key metabolic pathways associated with biodegradation of microplastics in reservoir sediments.


Lipid composition and fatty acid pattern of the gerbil brain after exposure to perchloroethylene.
Continuous inhalation of perchloroethylene (PCE) (320 ppm) for 3 months by Mongolian gerbils resulted in an altered fatty acid pattern of a brain phospholipid. A minor decrease in the brain weight was also observed. In ethanolamine phosphoglyceride of the cerebral cortex and the hippocampus, a decrease was found among the minor fatty acids derived from linolenic acid with a corresponding increase in several fatty acids of the linoleic acid family. Linoleic acid itself was decreased. Stearic acid was also decreased in both the cerebral cortex and the hippocampus. These changes in the fatty acid pattern indicate increased desaturation. PCE might alter the desaturase activity either directly by interfering with the protein moieties of the enzyme system, or indirectly by changing the properties of the lipid matrix. The observed changes in fatty acid composition are also consistent with the current hypothesis that solvents and anesthetics perturb the lipid matrix of membranes, possibly inducing complex compensatory changes in the membrane lipid composition.


Characterization of the elusive disulfide bridge forming human Hb variant: Hb Ta-Li beta83 (EF7)Gly --> Cys by electrospray mass spectrometry.
An electrospray mass spectrometric approach to the identification of a human hemoglobin (Hb) variant involving a Cys residue incorporation is presented. In Hb Ta-Li (beta83Gly --> Cys), Cys83 forms inter-molecular disulfide bridges. Routine analysis of the denatured Hb showed the presence of a minor beta chain variant whose mass apparently was 1 Da less than the expected mass difference of 46 Da for a Gly --> Cys substitution. Reduction of the globin chains with dithiothreitol gave an intense monomer with the expected mass difference for the Gly --> Cys substitution. After reprocessing the original raw data from the denatured Hb and taking into account the possibility of dimer formation, a component was revealed whose mass was consistent with a disulfide linked dimer of Ta-Li beta globins. The mutation was localized to peptide betaT10 by analysis of a tryptic digest. Tandem mass spectrometry and DNA sequencing confirmed the Gly --> Cys substitution occurred at residue 83 of the beta chain. Problems encountered in identifying the components in mixtures of monomers and dimers are discussed.


Lipids, Blood Pressure, and Diabetes Mellitus on Risk of Cardiovascular Diseases in East Asians: A Mendelian Randomization Study.
Elevated blood pressure, dyslipidemia, and impaired glycemic control are well-established cardiovascular risk factors in Europeans, but there are comparatively few studies focused on East Asian populations. This study evaluated the potential causal relations between traditional cardiovascular risk factors and disease risk in East Asians through a 2-sample Mendelian randomization approach. We collected summary statistics for blood pressure parameters, lipid subsets, and type 2 diabetes mellitus liability from large genome-wide association study meta-analyses conducted in East Asians and Europeans. These were paired with summary statistics for ischemic heart disease (IHD), ischemic stroke (IS), peripheral vascular disease, heart failure (HF) and atrial fibrillation (AF). We performed univariable Mendelian randomization analyses for each exposure-outcome pair, followed by multivariable analyses for the available lipid subsets. The genetically predicted risk factors associated with IHD and AF were similar between East Asians and Europeans. However, in East Asians only genetically predicted elevated blood pressure was significantly associated with IS (odds ratio 1.05, 95% confidence interval 1.04 to 1.06, p <0.0001) and HF (odds ratio 1.05, 95% confidence interval 1.04 to 1.06, p <0.0001), whereas nearly all genetically predicted risk factors were significantly associated with IS and HF in Europeans. In conclusion, this study provides supportive evidence for similar causal relations between traditional cardiovascular risk factors and IHD and AF in both East Asian and European ancestry populations. However, the identified risk factors for IS and HF differed between East Asians and Europeans, potentially highlighting distinct disease etiologies between these populations.