Nutrition and factors limiting the growth of a methanogenic bacterium (Methanobacterium thermoautotrophicum).
The purification of Methanobacterium thermoautotrophicum from a culture contaminated with a heterotrophic organism is described. A defined inorganic medium under H2/CO2 (80:20 v/v) has been developed to support growth of M. thermoautotrophicum up to a concentration of at least 1.7 g dry weight/l. In a conventional medium iron and nitrogen sources were found to be growth-limiting factors. Throughout most of the culture period the rate of transfer of hydrogen or carbon dioxide from gas to liquid was the factor which controlled the growth rate. The growth yields of bacteria were in the range of 0.6-1.6 g dry weight/mole CH4.


Development of a sustained release dosage form for alpha-lipoic acid. II. Evaluation in human volunteers.
Within this study an oral sustained release dosage form of alpha-lipoic acid (thioctic acid) has been generated and evaluated in healthy volunteers. A granulate comprising 56.8% alpha-lipoic acid and 43.2% chitosan acetate was compressed to tablets (weight: 0.45 g; diameter: 10.0 mm; thickness: 4 mm). Three of these tablets were administered at once orally to each volunteer. Prior to administration and then every hour for 12 hours blood samples were taken from the antebrachial vein. alpha-Lipoic acid concentrations in plasma were quantified via precolumn derivatization and reversed-phase high-performance liquid chromatography (HPLC). Results demonstrated that an increased plasma level of alpha-lipoic acid can be achieved by this formulation for at least 12 hours. Within this time period at least two maximum plasma concentrations were reached. The first one is based on the release of alpha-lipoic acid, which is not ionically and therefore only loosely bound to chitosan, whereas a second maximum is based on the release of the drug during the enzymatic degradation of the chitosan matrix in the colon. The AUC(0-12) was determined to be 183.8 +/- 101.4 microg x min/mL (mean +/- SD; n = 8). Because of the pulsed sustained release of alpha-lipoic acid, the dosage form described here seems to be highly beneficial in order to stimulate the glucose uptake in the case of diabetes type II.


PAG/Cbp suppression reveals a contribution of CTLA-4 to setting the activation threshold in T cells.
PAG/Cbp represents a ubiquitous mechanism for regulating Src family kinases by recruiting Csk to the plasma membrane, thereby controlling cellular activation. Since Src kinases are known oncogenes, we used RNA interference in primary human T cells to test whether the loss of PAG resulted in lymphocyte transformation. PAG-depletion enhanced Src kinase activity and augmented proximal T-cell receptor signaling; exactly the phenotype expected for loss of this negative regulator. Surprisingly, rather than becoming hyper-proliferative, PAG-suppressed T cells became unresponsive. This was mediated by a Fyn-dependent hyper-phosphorylation of the inhibitory receptor CTLA-4, which recruited the protein tyrosine phosphatase Shp-1 to lipid rafts. Co-suppression of CTLA-4 abrogates this inhibition and restores proliferation to T cells. We have identified a fail-safe mechanism as well as a novel contribution of CTLA-4 to setting the activation threshold in T cells.


Corneal Hysteresis and Progressive Retinal Nerve Fiber Layer Loss in Glaucoma.
To investigate the relationship between corneal hysteresis (CH) and progressive retinal nerve fiber layer (RNFL) loss in a cohort of patients with glaucoma followed prospectively over time. Prospective observational cohort study. One hundred and eighty-six eyes of 133 patients with glaucoma were followed for an average of 3.8 ± 0.8 years, with a median of 9 visits during follow-up. The CH measurements were acquired using the Ocular Response Analyzer (Reichert Instruments, Depew, New York, USA) and RNFL measurements were obtained at each follow up visit using spectral-domain optical coherence tomography (SDOCT). Random-coefficient models were used to investigate the relationship between baseline CH, central corneal thickness (CCT), average intraocular pressure (IOP), and rates of RNFL loss during follow-up, while adjusting for potentially confounding factors. Average baseline RNFL thickness was 76.4 ± 18.1 μm and average baseline CH was 9.2 ± 1.8 mm Hg. CH had a significant effect on rates of RNFL progression. In the univariable model, including only CH as a predictive factor along with time and their interaction, each 1 mm Hg lower CH was associated with a 0.13 μm/year faster rate of RNFL decline (P = .011). A similar relationship between low CH and faster rates of RNFL loss was found using a multivariable model accounting for age, race, average IOP, and CCT (P = .015). Lower CH was significantly associated with faster rates of RNFL loss over time. The prospective longitudinal design of this study provides further evidence that CH is an important factor to be considered in the assessment of the risk of progression in patients with glaucoma.


Activity-dependent modulation of synaptic AMPA receptor accumulation.
Both theoretical and experimental work have suggested that central neurons compensate for changes in excitatory synaptic input in order to maintain a relatively constant output. We report here that inhibition of excitatory synaptic transmission in cultured spinal neurons leads to an increase in mEPSC amplitudes, accompanied by an equivalent increase in the accumulation of AMPA receptors at synapses. Conversely, increasing excitatory synaptic activity leads to a decrease in synaptic AMPA receptors and a decline in mEPSC amplitude. The time course of this synaptic remodeling is slow, similar to the metabolic half-life of neuronal AMPA receptors. Moreover, inhibiting excitatory synaptic transmission significantly prolongs the half-life of the AMPA receptor subunit GluR1, suggesting that synaptic activity modulates the size of the mEPSC by regulating the turnover of postsynaptic AMPA receptors.


Free amino acid levels in amyotrophic lateral sclerosis.
To evaluate reports of abnormal levels of free amino acids (AA) in patients with amyotrophic lateral sclerosis (ALS), we studied serum, cerebrospinal fluid, and urine AA in 12 patients with ALS and 12 controls matched for age, sex, and severity of disability. ALS patients had statistically significant elevations in serum levels of tyrosine, total aromatic AA, and total basic AA. ALS patients also had statistically significant elevations in cerebrospinal fluid of total basic AA, lysine, essential AA, and leucine. The severity of ALS correlated inversely with acidic AA (glutamate and aspartate) and O-phosphoserine in cerebrospinal fluid. Activity of ALS correlated directly with serum aspartate and cerebrospinal fluid alanine. We conclude that subtle abnormalities of AA levels are present in ALS and that these are not due to age, sex, or disability. The pattern of distribution of AA levels differs from that in hepatic or renal disease and suggests defective membrane transport or poor cellular utilization of basic and essential AA in the central nervous system.


The mode of hydrolysis of a glycan portion of Micrococcus lysodeikticus cell walls by endo-N-acetylglucosaminidase or endo-N-acetylmuramidase isolated from crude barley beta-amylase.
Micrococcus lysodeikticus cell walls were digested with a pI 6.8 endo-N-acetylglucosaminidase or a pI 9.5 endo-N-acetylmuramidase. The digests were further treated with a N-acetylmuramyl-L-alanine amidase of Flavobacterium L-11 enzyme to remove the peptide portion. The products were fractionated by gel filtration and ion-exchange chromatography, and the glycan portion of fractions were analyzed for their average amino sugar chain lengths. The following results were obtained. 1. The glycan portion of the main products in the pI 6.8 enzyme digest consisted of (-N-acetylmuramic acid-N-acetyl-glucosamine-)2-3. 2. The glycan moiety of the pI 9.5 enzyme digest was mainly composed of (-N-acetylglucosamine-N-acetylmuramic acid-)3-4. 3. The glycosidic linkages around the muramic acid 6-phosphate residues which linked to a special structure through a phosphodiester bond were rather refractory to the glycosidase action of both pI 6.8 and 9.5 enzymes.


A Rare Case of Fibrous Hamartoma of Infancy: A Clinicopathological Diagnosis at a Tertiary Hospital, Eastern Nepal.
Fibrous hamartoma of infancy is a rare soft tissue lesion of infants and young children with characteristic triphasic morphology. An 18-month-old female child was presented with complaints of swelling over right leg shin since birth. On examination, a lump of size 7x3 cm was identified which was mobile and nontender. Local excision was performed and tissue sent for histopathological examination. On gross examination, a globular, capsulated, firm to hard tissue had cut section revealing solid grey-white to grey-brown lesion with myxoid areas identified. Microscopic examination revealed a poorly circumscribed lesion comprising intersecting trabeculae of fibrous tissue, areas of immature oval and stellate cell within myxoid matrix, and varying amounts of interspersed mature fat cells. Even though fibrous hamartoma of infancy is a rare benign entity with limited clinical knowledge, proper diagnosis is mandatory as its prognosis is excellent.


Primary spinal Non-Hodgkin Lymphoma presenting as impending cauda equina syndrome: A case report.
Malignant lymphoma (ML) can involve the central nervous system either primarily or by secondary spread, which tends to occur late in the disease as part of widespread dissemination. Lymphoma presenting as primary tumors of the spinal cord is extremely uncommon. Primary spinal lymphoma if detected early can have a good prognosis with no relapse after effective treatment. A 32 years old male patient presented with the symptoms of impending cauda equina syndrome which was managed with surgery and chemotherapy. The patient was successfully treated without the relapse of his condition at his 6 months follow-up scan.Discussion: Primary spinal non-Hodgkin lymphoma is a rare entity among extranodal non-Hodgkin lymphoma. MRI is usually non-confirmatory and needs immunohistochemistry for the correct diagnosis. R-CHOP regimen is the standard chemotherapy regimen. Surgical decompression is required in cases of impending neurological injury along with radiotherapy. Primary spinal epidural diffuse large B-cell lymphoma should be considered as a differential diagnosis in patients presenting with back pain and symptoms of impending cauda equina syndrome. It is important to early detect and treat the disease to prevent permanent neurological injury and metastasis.


Phosphatase-regulated recruitment of the spindle- and kinetochore-associated (Ska) complex to kinetochores.
Kinetochores move chromosomes on dynamic spindle microtubules and regulate signaling of the spindle checkpoint. The spindle- and kinetochore-associated (Ska) complex, a hexamer composed of two copies of Ska1, Ska2 and Ska3, has been implicated in both roles. Phosphorylation of kinetochore components by the well-studied mitotic kinases Cdk1, Aurora B, Plk1, Mps1, and Bub1 regulate chromosome movement and checkpoint signaling. Roles for the opposing phosphatases are more poorly defined. Recently, we showed that the C terminus of Ska1 recruits protein phosphatase 1 (PP1) to kinetochores. Here we show that PP1 and protein phosphatase 2A (PP2A) both promote accumulation of Ska at kinetochores. Depletion of PP1 or PP2A by siRNA reduces Ska binding at kinetochores, impairs alignment of chromosomes to the spindle midplane, and causes metaphase delay or arrest, phenotypes that are also seen after depletion of Ska. Artificial tethering of PP1 to the outer kinetochore protein Nuf2 promotes Ska recruitment to kinetochores, and it reduces but does not fully rescue chromosome alignment and metaphase arrest defects seen after Ska depletion. We propose that Ska has multiple functions in promoting mitotic progression and that kinetochore-associated phosphatases function in a positive feedback cycle to reinforce Ska complex accumulation at kinetochores.


[Study on the role of interleukin-5 and eosinophil cationic protein and the correlation between them in nasal polyp].
To evaluate the degree of recruitment and activation of eosinophils; to confirm the concentration and expression of IL-5 in nasal polyps; to study the correlation between eosinophilic activation and cytokine such as IL-5. Blood and nasal specimens were collected from 30 patients with nasal polyps and 8 controls with deviation of nasal septum or OSAS. The serum ECP levels in two groups and the IL-5 and ECP in nasal polyp specimens or inferior turbinate mucosa were examined. Concentration of IL-5 and ECP in nasal polyps tissue homogenates were significantly higher than those in inferior turbinate mucosas (P < 0.05). The same result was showed in serum ECP. The elevated IL-5 levels in polyp homogenates had a significant correlation with serum ECP(r = 0.598, P < 0.05) and polyp tissues ECP(r = 0.451, P < 0.05). The concentration of IL-5 increased in the nasal polyp tissues and the degree of expression showed a significant correlation with activated eosinophils.


Dealing with impact of COVID-19 on transportation in a developing country: Insights and policy recommendations.
While developed nations have established policy frameworks for dealing with various macroeconomic shocks, developing countries respond to the influx of COVID-19 on heterogeneous scales, borne out of varying institutional bottlenecks. These inadequate transport facilities are not diversified enough to deal with an impending public health crisis. With the growing divergence in public transport management procedures and societal responses and willingness to adjust to a "new normal" transport procedures in time of COVID-19 and post-pandemic, it becomes expedient to learn evidence-based policy responses to transport service delivery. Qualitative data from semi-structured interviews with commuters and operators were thematically analysed to understand the impact of COVID-19 on transportation in Lagos Nigeria. The analysis revealed that increased cost of transportation, financial sustainability, changes in travel needs and loss of revenue were the significant impacts of the pandemic. This study contributes such that transport stakeholders can better understand how to navigate their transportation needs at this time of global uncertainty. The understanding of these impacts advances policy recommendations that are most inclined to the development objectives of developing nations in the time of COVID-19 and beyond. The limitations and suggestions for further research were discussed.


Synthesis and evaluation of in vitro antiviral activity of novel phenoxy acetic acid derivatives.
Several substituted phenoxy acetic acid derived pyrazolines were synthesized by the reaction between 2-{4-[3-(2,4-dihydroxyphenyl)-3-oxo-1-propenyl]-2-methoxyphenoxy} acetic acid and substituted acid hydrazides and were tested for their in vitro cytotoxicity and antiviral activity. None of the compounds showed any specific antiviral activity [50% antivirally effective concentration (EC(50)) > or = 5-fold lower than minimum cytotoxic concentration]. The most cytotoxic of the series was 2-{4-[3-(2,4-dihydroxyphenyl)-1-(2-hydroxybenzoyl-4,5-dihydro-1H-5-pyrazolyl]-2-methoxyphenoxy}acetic acid (3(j)), with a minimum cytotoxic concentration of 0.16 microg/mL in human embryonic lung (HEL) cells.


Peripheral sensory nerve function, type 2 diabetes and frailty among men with cardiovascular disease.
To investigated the cross-sectional association between peripheral sensory nerve function and frailty among community-dwelling men, and examine whether type 2 diabetes (T2D) modifies this association. A sample of 349 men [mean age = 77.1 ± 6.4 years; 37 % with T2D] who previously (1990-1998) participated in the Bezafibrate Infarction Prevention (BIP) trial, underwent assessment of frailty and legs vibratory thresholds (LVT), a measure of peripheral sensory nerve function, as part of the BIP Neurocognitive study during 2011-2013. LVT was assessed using a graduated tuning fork and frailty was assessed using the Fried criteria. An ordered logistic regression model was used to assess the link between LVT and degrees of frailty and to test for effect modification by T2D. Overall, 117 (33.5 %) of patients were non-frail, 134 (38.4 %) pre-frail, and 98 (28.1 %) frail. A significant interaction between LVT and T2D with regard to frailty was found. Among men with T2D, estimated OR (95%CI) for increasing frailty at the 1st, 2nd, and 3rd as compared to the top LVT quartile were 13.5 (3.4-54.3), 5.9 (1.5-23.5), and 4.4 (1.20-16.0), respectively. Among men without T2D, the estimated ORs for increasing frailty in patients at the 1st, 2nd, and 3rd quartiles compared to the top LVT quartile were 2.8 (1.1-7.4), 1.6 (0.6-4.1), and 2.5 (1.0-6.5), respectively. Frailty is significantly associated with worsening peripheral sensory nerve function, particularly among men with T2D.


Proton MR spectroscopy of basal ganglia in Wilson's disease: case report and review of literature.
Volume localized proton Magnetic Resonance Spectroscopy was carried out in both the left and right basal ganglia of three patients with clinically proven Wilson's Disease. While the untreated patient died 15 days after the spectroscopy study, the other 2 patients have been under treatment and have shown clinical improvement. The spectral features of the untreated patient were very different from those of the other two patients who were under treatment and responding. Asymmetrical changes in NAA and Cho were also observed for this patient.


Bone bridge technique for lateral meniscal allograft transplantation: no difference in clinical outcome compared to the soft tissue technique.
There is considerable debate regarding the optimal method of fixation for lateral meniscus allograft transplantation (MAT), with bone bridge techniques technically harder but allowing maintenance of root attachments, while soft tissue techniques are potentially more challenging for healing. The aim of this study was to compare the clinical results of the bone bridge and soft tissue techniques for lateral MAT in terms of failure, re-operation rate, complications and patient reported outcomes. Retrospective analysis of prospectively collected data for patients undergoing primary lateral MAT with a minimum of 12-month follow-up. Patients following surgery utilising the bone bridge technique (BB) were compared with historical control patients who underwent MAT with the soft tissue technique (ST). Outcome was assessed by failure rate, defined as removal or revision of the meniscus transplant, survivorship by Kaplan-Meir analysis, re-operation rates, and other adverse event. Patient-reported outcome measures (PROMs) were compared using data at the 2-year point or 1 year if not reached 2 years. One-hundred and twelve patients following lateral meniscal transplants were included, 31 in the BB group and 81 in the ST historical control group, with no differences in demographics between both groups. Median follow-up for the BB group was 18 (12-43) months compared to 46 (15-62) months for the ST group. There were 3 failures (9.6%) in the BB group v 2 (2.4%) in the ST group (n.s.) with a mean time to failure of 9 months in both groups. 9 patients (29%) required a re-operation (all cause) in the BB group v 24 patients (29.6%) in the ST group (n.s). There was no difference in complications between both groups. There was significant improvement (p < 0.0001) in all PROMs (Tegner, IKDC, KOOS and Lysholm) between baseline and 2-year follow-up for both groups but no between-group differences. Lateral MAT has a high success rate for symptomatic meniscal deficiency with significant benefits irrespective of the fixation technique. There is no advantage in performing the more technically demanding BB technique over ST fixation. Level 2.


Oxidative stress as an etiological factor and a potential treatment target of psychiatric disorders. Part 1. Chemical aspects and biological sources of oxidative stress in the brain.
Oxidative stress is a dysfunctional state of living cells, caused by the disturbance of the pro-/antioxidative equilibrium. This dynamic equilibrium, constitutive for all aerobic organisms, is an inevitable necessity of maintaining the level of oxidative factors on non-destructive value to the cell. Among these factors reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the best known molecules. This review article shows the current state of knowledge on the chemical specificity, relative reactivity and main sources of ROS and RNS in biological systems. As a Part 1 to the report about the role of oxidative stress in psychiatric disorders (see Smaga et al., Pharmacological Reports, this issue), special emphasis is placed on biochemical determinants in nervous tissue, which predisposed it to oxidative damage. Oxidative stress can be identified based on the analysis of various biochemical indicators showing the status of antioxidant barrier or size of the damage. In our article, we have compiled the most commonly used biomarkers of oxidative stress described in the literature with special regard to potentially effective in the early diagnosis of neurodegenerative processes.


VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond.
Despite the enormous progress made in terms of prevention and early intervention, a pressing need remains to develop innovative therapeutic strategies for ischemic cardiovascular disorders, including acute myocardial infarction, chronic cardiac ischemia, peripheral artery disease and stroke. The induction of new blood vessel formation by delivering angiogenic genes to ischemic tissues continues to appear as a promising, alternative strategy to currently available therapies. In aspiring to induce therapeutic angiogenesis, the members of the vascular endothelial growth factor (VEGF) family have long been recognized as major molecular tools. Remarkably, VEGF family members have recently been recognized to also exert multiple, non-angiogenic effects on various cell types, including neurons, skeletal muscle and cardiac cells. Here, we critically review the VEGF-based therapies that have already reached clinical experimentation and highlight the pleiotropic activities of VEGF factors that might create new opportunities for therapeutic application.


Retroperitoneal myxoid variant of malignant fibrous histiocytoma: report of a case.
A case of a retroperitoneal myxoid variant of malignant fibrous histiocytoma is reported. The chief complaints were remittent fever and a painful mass on the right flank, which were misdiagnosed as acute inflammatory disease.


Role of unfolded protein response and ER-associated degradation under freezing, anoxia, and dehydration stresses in the freeze-tolerant wood frogs.
The North American amphibian, wood frogs, Rana sylvatica are the most studied anuran to comprehend vertebrate freeze tolerance. Multiple adaptations support their survival in frigid temperatures during winters, particularly their ability to produce glucose as natural cryoprotectant. Freezing and its component consequences (anoxia and dehydration) induce multiple stresses on cells. Among these is endoplasmic reticulum (ER) stress, a condition spawned by buildup of unfolded or misfolded proteins in the ER. The ER stress causes the unfolded protein response (UPR) and the ER-associated degradation (ERAD) pathway that potentially could lead to apoptosis. Immunoblotting was used to assess the responses of major proteins of the UPR and ERAD under freezing, anoxia, and dehydration stresses in the liver and skeletal muscle of the wood frogs. Targets analyzed included activating transcription factors (ATF3, ATF4, ATF6), the growth arrest and DNA damage proteins (GADD34, GADD153), and EDEM (ERAD enhancing α-mannosidase-like proteins) and XBP1 (X-box binding protein 1) proteins. UPR signaling was triggered under all three stresses (freezing, anoxia, dehydration) in liver and skeletal muscle of wood frogs with most tissue/stress responses consistent with an upregulation of the primary targets of all three UPR pathways (ATF4, ATF6, and XBP-1) to enhance the protein folding/refolding capacity under these stress conditions. Only frozen muscle showed preference for proteasomal degradation of misfolded proteins via upregulation of EDEM (ERAD). The ERAD response of liver was downregulated across three stresses suggesting preference for more refolding of misfolded/unfolded proteins. Overall, we conclude that wood frog organs activate the UPR as a means of stabilizing and repairing cellular proteins to best survive freezing exposures.


A novel endothelial function test using Doppler flow: the snuff-box technique.
Precise measurement of Doppler estimated blood flow volume using the standard technique of flow-mediated vasodilation is not possible because the anatomic course of the brachial or radial artery goes against the principle of Doppler measurements that the insonation angle should be less than 30 degrees . The radial artery in the anatomic snuff-box area is useful for the measurement of Doppler signals as the insonation angle is less than 30 degrees and because the size of the artery allows observation of laminar flow. We introduce the snuff-box technique as a novel endothelial function test that enables measurement of both blood flow and diameter of the radial artery. Changes in diameter and blood flow volume during reactive hyperemia were examined in 15 healthy volunteers. Changes in blood flow determined using the snuff-box technique were compared with changes in forearm blood flow determined by plethysmography. The diameter of the radial artery increased from 2.3 +/- 0.2 mm at baseline to 2.8 +/- 0.4 mm at 60 s after deflation (P = 0.0017), and blood flow increased from 52.3 +/- 21.4 ml/min at baseline to 108.6 +/- 33.1 ml/min at 15 s after deflation (P = 0.0014). Percentile blood flow determined by the snuff-box technique correlated significantly with that determined by plethysmography (r = 0.824, P = 0.0002). Both blood flow volume and artery diameter can be measured with high reliability using the snuff-box technique, as has been shown in subjects with reactive hyperemia.


Aquatic life and its parallelsHow Far the Light Reaches: A Life in Ten Sea Creatures Sabrina Imbler Little, Brown, 2022. 320 pp.
Blurring the personal and the scientific, an author probes the beauty, terror, and richness of the natural world.


[Arthroscopic treatment of chondropathia patellae with lateral release and motor driven instruments].
The treatment of chondromalacia of the patella is a medical problem. There are no sure concepts of therapy. We have analysed the value of the only lateral release or shaving by motorizised instruments or the combination of both methods. After lateral release have many patients no pain but the other methods also helped many patients. The comparison of these groups is impossible because of the different structure. A prospective randomised study has to bring the answer to this question.


Right ventricular apical view--a new window for Doppler echocardiography of aortic valve stenosis.
We studied a new Doppler echocardiographic approach in 56 patients with valvular aortic stenosis from the right ventricular apex (AS-RV) and compared the transvalvular gradients with the results of the standard view from the left ventricular apex (AS-LV). AS-RV resulted in good or acceptable velocity curves in 59% of patients. The correlation between the two apical views for the peak/mean gradients were close (r = 0.95/0.96). Using all typical positions for Doppler investigation of aortic stenosis, highest peak gradients were best recorded in five cases by AS-RV. In one woman with a narrow left ventricular cavum and severe aortic stenosis, only AS-RV yielded a technically good spectral curve. Thus, in selected patients--probably those with a small left ventricular cavity or an enlarged right ventricle--AS-RV may be the best window or even the only possibility in Doppler investigation of aortic valve stenosis.


[Changes in the clinical electromyographic indices of patients with the hyperkinetic form of infantile cerebral palsy and their dynamics during combined sanatorium-health resort treatment including transcerebral exposure to an ultrahigh-frequency electrical field].
Clinical electromyographic studies were made to evaluate the efficacy of transcerebral exposure to UHF electric field which has been used as an adjuvant to therapeutic exercise, massage, climate treatment in 33 patients with hyperkinetic infantile cerebral paralysis (ICP). The effect on the motor disorders reached 70.8%. Specific features of statokinetic function in hyperkinetic ICP children recorded electromyographically dictate combined use of various modalities (therapeutic exercises, preformed physical factors, games, reflex therapy, etc.) to improve therapeutic actions on vestibular apparatus.


Focal MRI and Learning Disability with Reduced Automaticity.
Investigators from the Boston Children's Hospital, Harvard Medical School, MA, performed a retrospective analysis of 1,587 children referred for a learning disability, and 127 had a focal deficit demonstrated on either a neurologic or neuropsychological evaluation.


Chemical modification of triplex-forming oligonucleotide to promote pyrimidine motif triplex formation at physiological pH.
Extreme instability of pyrimidine motif triplex DNA at physiological pH severely limits its use in wide variety of potential applications, such as artificial regulation of gene expression, mapping of genomic DNA, and gene-targeted mutagenesis in vivo. Stabilization of pyrimidine motif triplex at physiological pH is, therefore, crucial for improving its potential in various triplex-formation-based strategies in vivo. To this end, we investigated the effect of 3'-amino-2'-O,4'-C-methylene bridged nucleic acid modification of triplex-forming oligonucleotide (TFO), in which 2'-O and 4'-C of the sugar moiety were bridged with the methylene chain and 3'-O was replaced by 3'-NH, on pyrimidine motif triplex formation at physiological pH. The modification not only significantly increased the thermal stability of the triplex but also increased the binding constant of triplex formation about 15-fold. The increased magnitude of the binding constant was not significantly changed when the number and position of the modification in TFO changed. The consideration of the observed thermodynamic parameters suggested that the increased rigidity of the modified TFO in the free state resulting from the bridging of different positions of the sugar moiety with an alkyl chain and the increased hydration of the modified TFO in the free state caused by the introduction of polar nitrogen atoms may significantly increase the binding constant at physiological pH. The study on the TFO viability in human serum showed that the modification significantly increased the resistance of TFO against nuclease degradation. This study presents an effective approach for designing novel chemically modified TFOs with higher binding affinity of triplex formation at physiological pH and higher nuclease resistance under physiological condition, which may eventually lead to progress in various triplex-formation-based strategies in vivo.


Emerging Viral and Bacterial Infections: Within an Era of Opioid Epidemic.
The opioid epidemic is a public health crisis that continues to impact healthcare in the United States of America (USA). While changes in opioid prescribing have curbed the medical use of opioids, the increase in nonmedical use, largely driven by injection drug use (IDU), has contributed to the escalating incidence of opioid use disorder (OUD). Furthermore, IDU is associated with high-risk injection practices that can increase the risk of acquiring viral and bacterial infections. Here in this comprehensive review, we aimed to summarize the epidemiology and management of OUD, along with the screening and antimicrobial treatment of associated infections, specifically focused on human immunodeficiency virus, hepatitis C virus, skin and soft tissue infections, endocarditis, and osteomyelitis. Medication-assisted therapy (MAT) and infection guidelines from the USA will be presented.


Comparison of outcomes and donor-site morbidity in unilateral free TRAM versus DIEP flap breast reconstruction.
At long-term follow up we cannot easily differentiate between patients who have undergone free transverse rectus abdominis musculocutaneous (TRAM) flap and deep inferior epigastric artery perforator (DIEP) flap breast reconstruction in terms of subjective functional limitations of daily activities. The aim of this study was to evaluate postoperative outcomes and long-term subjective functional deficit in patients following unilateral free TRAM compared with DIEP flap breast reconstruction. Sixty consecutive patients who underwent unilateral autologous breast reconstruction were included in the study, 30 of whom had undergone a DIEP flap, and 30 a free TRAM flap. Surgical and postoperative outcome data were collected and a postal questionnaire was sent to each patient at least 6 months postoperatively consisting of a short functional assessment questionnaire and a Short Form 36 (SF-36) survey. We found no significant difference in postoperative outcomes or in the subjective ability to perform activities of daily living, including work, domestic activities, sports and hobbies, between patients who underwent TRAM flap breast reconstruction and those who underwent a DIEP flap, and no significant difference between the groups for scores on the physical functioning, role-physical, or bodily pain scales of the SF-36. We conclude that harvesting of the free TRAM flap results in no significant difference in postoperative outcomes or in the subjective ability to perform activities of daily living compared with the DIEP flap.


Abortion and anxiety: what's the relationship?
Using data from the United States National Survey of Family Growth (NSFG) and the National Comorbidity Survey (NCS), we conducted secondary data analyses to examine the relationship of abortion, including multiple abortions, to anxiety after first pregnancy outcome in two studies. First, when analyzing the NSFG, we found that pre-pregnancy anxiety symptoms, rape history, age at first pregnancy outcome (abortion vs. delivery), race, marital status, income, education, subsequent abortions, and subsequent deliveries accounted for a significant association initially found between first pregnancy outcome and experiencing subsequent anxiety symptoms. We then tested the relationship of abortion to clinically diagnosed generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), and social anxiety disorder, using NCS data. Contrary to findings from our analyses of the NSFG, in the NCS analyses we did not find a significant relationship between first pregnancy outcome and subsequent rates of GAD, social anxiety, or PTSD. However, multiple abortions were found to be associated with much higher rates of PTSD and social anxiety; this relationship was largely explained by pre-pregnancy mental health disorders and their association with higher rates of violence. Researchers and clinicians need to learn more about the relations of violence exposure, mental health, and pregnancy outcome to avoid attributing poor mental health solely to pregnancy outcomes.


Sidedness of the ATP-Na+-K+ interactions with the Na+ pump in squid axons.
Using dialysed squid axons we have been able to control internal and external ionic compositions under conditions in which most of the Na+ efflux goes through the Na+ pump. We found that (i) internal K+ had a strong inhibitory effect on Na+ efflux; this effect was antagonized by ATP, with low affinity, and by internal Na+, (ii) a reduction in ATP levels from 3 mM to 50 microM greatly increased the apparent affinity for external K+, but reduced its effectiveness compared with other monovalent cations, as an activator of Na+ efflux, and (iii) the relative effectiveness of different K+ congeners as external activator of the Na+ efflux, though affected by the ATP concentration, was not affected by the Na+/K+ ratio inside the cells. These results are consistent with the idea that the same conformation of the (Na+ + K+)-ATPase can be reached by interaction with external K+ after phosphorylation and with internal K+ before rephosphorylation. They also stress a nonphosphorylating regulatory role of ATP.


"We need more big trees as well as the grass roots": going beyond research capacity building to develop sustainable careers in mental health research in African countries.
There are substantial gaps in our knowledge regarding the aetiology of mental, neurological and substance use disorders in sub-Saharan Africa, and the cost-effectiveness and scalability of interventions to reduce the burden of these conditions on the continent. To address these gaps, international investment has focussed on building research capacity, including funding doctoral students in African countries, to support development of high quality, contextually relevant interventions. Absent, however, is an understanding of how capacity building feeds into research careers. Within a broader mental health research capacity-building initiative (African Mental Health Research Initiative), we conducted 52 qualitative interviews with early-career researchers, policymakers, academics, and service users from four African countries (Ethiopia, Malawi, South Africa, and Zimbabwe) and with international funders of mental health research. The interview guide focused on the research context, planning, and priorities and how respondents perceive research careers and funding. Thematic analysis was applied to the transcribed interviews. Five components of a research career emerged: (i) research positions; (ii) research skills; (iii) funding; (iv) research commitment from African countries; and (v) advocacy. All stakeholders wanted more high-impact African researchers, but few saw a clear, replicable track for developing their careers within universities or their Ministries of Health in their African countries. This stemmed, in part, from the lack of support for infrastructure that enables high-quality research: grants administration, mentorship, university leadership, research culture, and open communication between policymakers and researchers. This study highlights the importance of developing research infrastructure alongside capacity-building efforts. International funders should invest in grant management at African universities which would place them at the centre of research initiatives. African universities should prioritise the creation of a research culture by developing and promoting well-defined research tracks for both clinicians and academics, investing in grant management, and raising the profile of research within their institutions.


Seasonal root growth in the arctic tussock tundra.
The quantity of growing root tips per unit of soil volume was analyzed in a central Alaskan tussock tundra site. By June 10, the aboveground fraction of the vegetation had initiated the flush of spring growth and flowering while less than 5 active root tips cm-3 were found. By June 25 this value had increased to 30 root tips cm-3. Similar values in July were followed by a complete cessation of root growth after the first week of August. By then, leaf senescence had also become visible. In the spring, low root temperatures were responsible for the time lag between shoot growth initiation and the beginning of root growth. In early August, root growth stopped in spite of adequate soil temperatures and accumulated carbohydrate for root growth. It is proposed that use of reserve carbohydrate for root growth in August would compromise the flush of spring growth in the following year.


Variation in foliar uptake of polycyclic aromatic hydrocarbons in six varieties of winter wheat.
To investigate intraspecific variations of foliar uptake of polycyclic aromatic hydrocarbons (PAHs) of winter wheat (Triticum aestivum L.), leaves of six varieties including Changwu 521 (CW), Hedong TX-006 (HD), Jiaomai 266 (JM), Xiaoyan 22 (XY), Yunong 949 (YN), and Zhongmai 175 (ZM) were exposed to three levels of (0, 0.25, and 1.5 mg L-1) mixture of six selected PAHs (phenanthrene, anthracene, pyrene, benz[a]anthracene, benzo[a]pyrene, and benzo[g,h,i]perylene). After 10 consecutive days of application, all the six selected PAHs (Σ6 PAHs) were determined in the leaves of the six varieties of the winter wheat. There were apparent intraspecific differences in foliar uptake of PAHs in the winter wheat. The highest concentrations of Σ6 PAHs in the leaves of YN variety (64.6 mg kg-1) were approximate two times of the lowest concentrations in the leaves of HD variety (29.6 mg kg-1). Both individual PAHs and Σ6 PAHs in the cuticular waxes were significantly (p < 0.01) higher than those in leaves and far higher than those in roots, indicating that the cuticular waxes could play significant role in foliar uptake of PAHs. The present results also showed that the concentrations PAHs in leaves were positively (p < 0.05) correlated with the water solubility of the six selected PAHs. In addition, the present study suggested that there was basipetal translocation of PAHs in the winter wheat after foliar application of PAHs, although the mechanism was yet to be further studied.


ATM inhibition drives metabolic adaptation via induction of macropinocytosis.
Macropinocytosis is a nonspecific endocytic process that may enhance cancer cell survival under nutrient-poor conditions. Ataxia-Telangiectasia mutated (ATM) is a tumor suppressor that has been previously shown to play a role in cellular metabolic reprogramming. We report that the suppression of ATM increases macropinocytosis to promote cancer cell survival in nutrient-poor conditions. Combined inhibition of ATM and macropinocytosis suppressed proliferation and induced cell death both in vitro and in vivo. Supplementation of ATM-inhibited cells with amino acids, branched-chain amino acids (BCAAs) in particular, abrogated macropinocytosis. Analysis of ATM-inhibited cells in vitro demonstrated increased BCAA uptake, and metabolomics of ascites and interstitial fluid from tumors indicated decreased BCAAs in the microenvironment of ATM-inhibited tumors. These data reveal a novel basis of ATM-mediated tumor suppression whereby loss of ATM stimulates protumorigenic uptake of nutrients in part via macropinocytosis to promote cancer cell survival and reveal a potential metabolic vulnerability of ATM-inhibited cells.


Effects of low-temperature plasma treatment on pulmonary function in children with obstructive sleep apnea-hypopnea syndrome.
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common sleep-related respiratory disease. Despite reports of low-temperature plasma radiofrequency ablation of tonsils and adenoids for the treatment of OSAHS, the effects on lung function and quality of life are unclear. This study aims to explore the effects of low-temperature plasma treatment on pulmonary function in children with OSAHS. A total of 110 children with OSAHS were included in this prospective study. Low-temperature plasma radiofrequency treatment and routine surgical treatment were performed in group A and group B, respectively. Maximal voluntary ventilation (MVV), forced vital capacity (FVC), and total lung capacity (TLC) were measured. OSA-18 survey was used to evaluate the quality of life 1 year after operation. Group A had significantly higher effective treatment rate (P < 0.05) and lower operative period, bleeding volume, visual analog score, pseudomembrane detachment time, and time required to feed after operation than group B (all P < 0.001). There were no significant difference in the incidence of postoperative complications between the groups and MVV, FVC, and TLC between the groups before and after operation (all P > 0.05), and the above indexes in both groups were significantly increased after operation (all P < 0.05). OSA-18 scores in group A were significantly lower than group B after operation (P < 0.001). Low-temperature plasma technique performed in OSAHS children has a good clinical effect, which can reduce the operation time, intraoperative blood loss, postoperative pain, pseudomembrane detachment time, hospitalization time, and improve pulmonary function and quality of life.


Results of evaluation of 203 patients for photosensitivity in a 7.3-year period.
Although photosensitivity disorders have been well described, their incidence in a referral institution had not been studied. The purpose of this study was to evaluate the incidence of photosensitivity disorders, including photocontact dermatitis, in an academic medical center. The results of the assessment of 203 consecutive patients, all of whom had phototests, referred for the evaluation of photosensitivity disorders during a 7.3-year period were reviewed. The mean age was 50 years, and 63% of the patients were women. The most frequent diagnoses were polymorphous light eruption (26% of the total patient population), chronic actinic dermatitis (17%), photoallergic contact dermatitis (8%), systemic phototoxicity to therapeutic agents (7%), and solar urticaria (4%). Positive photopatch reactions, patch test reactions, or both were observed in 40 (29%) of the 138 tested patients. The frequencies of the positive photopatch test reactions were sunscreens (57%), fragrances (18%), and antimicrobial agents (13%). Of the positive patch test responses, fragrances elicited 47% of the total positive reactions, followed by sunscreens (39%) and antimicrobial agents (7%). Polymorphous light eruption, chronic actinic dermatitis, and photoallergic contact dermatitis were the most frequently made diagnoses. Sunscreens, fragrances, and antimicrobial agents were the most common clinically relevant photoallergens and allergens.


Comparative genomic analyses reveal the genetic basis of the yellow-seed trait in Brassica napus.
Yellow-seed trait is a desirable breeding characteristic of rapeseed (Brassica napus) that could greatly improve seed oil yield and quality. However, the underlying mechanisms controlling this phenotype in B. napus plants are difficult to discern because of their complexity. Here, we assemble high-quality genomes of yellow-seeded (GH06) and black-seeded (ZY821). Combining in-depth fine mapping of a quantitative trait locus (QTL) for seed color with other omics data reveal BnA09MYB47a, encoding an R2R3-MYB-type transcription factor, as the causal gene of a major QTL controlling the yellow-seed trait. Functional studies show that sequence variation of BnA09MYB47a underlies the functional divergence between the yellow- and black-seeded B. napus. The black-seed allele BnA09MYB47aZY821, but not the yellow-seed allele BnA09MYB47aGH06, promotes flavonoid biosynthesis by directly activating the expression of BnTT18. Our discovery suggests a possible approach to breeding B. napus for improved commercial value and facilitates flavonoid biosynthesis studies in Brassica crops.


Association study of common genetic variants in pre-microRNAs in patients with ulcerative colitis.
Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human diseases. We evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444) in pre-miRNAs (miR-196a2, miR-146a, and miR-499) with the risk of ulcerative colitis (UC) in a Japanese population. The rs11614913 (T > C), rs2910164 (C > G), and rs3746444 (A > G) SNPs were genotyped in 170 UC and 403 control subjects. The rs3746444 AG genotype was significantly higher among the UC group (odds ratio (OR) = 1.51, 95% CI = 1.03-2.21, p = 0.037). The rs3746444 AG genotype was associated with onset at an older age (OR = 1.70, 95% CI = 1.04-2.78, p = 0.035), left-sided colitis and pancolitis (left-sided colitis, OR = 2.10, 95% CI = 1.12-3.94, p = 0.024; pancolitis, OR = 1.81, 95% CI = 1.09-3.01, p = 0.028, left-sided colitis + pancolitis, OR = 1.91, 95% CI = 1.26-2.92, p = 0.003), higher number of times hospitalized (OR = 2.63, 95% CI = 1.22-5.69, p = 0.017), steroid dependence (OR = 2.63, 95% CI = 1.27-5.44, p = 0.014), and refractory phenotypes (OR = 2.76, 95% CI = 1.46-5.21, p = 0.002) while the rs3746444 AA genotype was inversely associated with the number of times hospitalized (2∼, OR = 0.36, 95% CI = 0.17-0.79, p = 0.012), steroid dependence (OR = 0.42, 95% CI = 0.21-0.88, p = 0.021), and refractory phenotypes (OR = 0.38, 95% CI = 0.20-0.72, p = 0.003). The rs1161913 TT genotype also held a significantly higher risk of refractory phenotype (T/T vs. T/C + C/C, OR = 2.21, 95% CI = 1.17-4.18, p = 0.016). Our results provided the first evidence that rs3746444 SNP may influence the susceptibility to UC, and both rs3746444 and rs11614913 SNPs may influence the pathophysiological features of UC.


Effect of an injectable trace mineral supplement containing selenium, copper, zinc, and manganese on the health and production of lactating Holstein cows.
The objective of this study was to evaluate the effect of a subcutaneous injection of a multimineral preparation containing 300 mg of zinc, 50mg of manganese, 25mg of selenium, and 75 mg of copper at 230 and 260 days of gestation and 35 days postpartum, on the health, milk production and reproductive performance of lactating Holstein cows. A randomized field trial was conducted on three large commercial dairy farms located near Ithaca, New York, USA, with 1416 cows enrolled. All cows were housed and offered a total mixed ration consisting of approximately 55% forage and 45% concentrate on a dry matter basis of the diet, which supplied 2-6 times the NRC requirements for the supplemented elements. Dry cows and pregnant heifers were blocked by parity and randomly allocated to one of two treatments: Trace mineral supplemented (TMS) or control. For multiparous cows, subcutaneous TMS significantly decreased linear somatic cell count scores (normalized data) as compared to control cows. The incidence of subclinical mastitis for TMS and control cows was 10.4% and 8.0%, respectively (P=0.005). The main effect of treatment on clinical mastitis was not significant but the interaction of treatment and parity was significant. For primiparous cows, the incidence of clinical mastitis was 11.8% and 15.6% for control and TMS cows, respectively (P=0.33); for multiparous cows, the incidence of clinical mastitis for control and TMS cows was 25.4% and 19.7%, respectively (P=0.03). Additionally, control cows had increased odds of stillbirth and endometritis (odds ratios 1.69 and 1.30, respectively). The incidence of endometritis was 34.2% and 28.6% for control and TMS cows, respectively (P=0.039) but treatment had no effect on reproductive performance, milk production or other health traits. Further research is required to confirm these findings and to establish whether the response seen in this study was related to the supplementation of a particular mineral.


The expression of late infantile neuronal ceroid lipofuscinosis (CLN2) gene product in human brains.
We raised polyclonal antibodies against a gene product responsible for late infantile neuronal ceroid lipofuscinosis (CLN2). By Western blotting, all three antisera recognized the CLN2 protein at approximately 49 kDa in human brain homogenates. Immunohistochemistry using the antisera demonstrated the granular labelling in the cytoplasm of cerebral neurons and glial cells. The immunoreactivity on Western blots was absent from the brain of a patient with CLN2. Our results suggest the usefulness of these antibodies for the diagnosis of CLN2, which currently requires demonstration of characteristic ultrastructure by electron microscopy.


The L2/HNK-1 carbohydrate mediates adhesion of neural cells to laminin.
The L2/HNK-1 carbohydrate epitope shared by several neural adhesion molecules has been implicated in cell-to-cell and cell-to-laminin adhesion (Keilhauer et al., Nature, 316, 728-730, 1985; Künemund et al., J. Cell Biol., 106, 213-223, 1988). As demonstrated previously for chicken retinal ganglion cells (Cole et al., Neurosci. Lett., 93, 170-175, 1988), cerebral cortex astrocytes or cerebellar neurons could not be shown to adhere to the substrate-bound L2/HNK-1 carbohydrate. The cell-bound L2/HNK-1 carbohydrate, however, was a potent mediator of astrocytic and neuronal cell adhesion to laminin, which was strongly reduced in the presence of the L2/HNK-1 carbohydrate-carrying glycolipids or Fab fragments of a monoclonal antibody against it. Inhibition of adhesion could not be observed in the presence of the negatively charged gangliosides or sulphatide, but in the presence of heparin. To investigate whether the L2/HNK-1 carbohydrate and heparin use the same or different binding sites on laminin, adhesion of cells to laminin was determined in the presence of heparin and Fab fragments of a monoclonal L2 antibody, which gave an additive value of inhibition as compared to the inhibition caused by the single compounds. This result, as well as studies of the binding of the L2/HNK-1 glycolipids to laminin in the presence of heparin, indicates that the L2/HNK-1 carbohydrate and heparin are implicated in different aspects of neural cell adhesion to laminin.


Genetically obese Zucker rats have abnormally low brain insulin content.
The concentration of immunoreactive insulin (IRI) extracted from the olfactory bulb, hypothalamus, hippocampus, cerebral cortex, amygdala, midbrain, and hindbrain was significantly lower in obese (fa/fa) and heterozygous (Fa/fa) Zucker rats in comparison to lean (Fa/Fa) Zucker rats. This deficit in brain IRI content was most severe in the hypothalamus and olfactory bulb and was independent of severe obesity since the marked reduction of brain IRI content was also found in heterozygous rats which possessed only one copy of the fa allele. These results demonstrate that in the 2-3 month-old female Zucker rat, the fa allele is associated with defective regulation of insulin in the brain.


Effect of phosphorylation in vitro of human fibrinogen with protein kinase C on thrombin-induced gelation.
Thrombin-induced gel formation of fibrinogen phosphorylated by protein kinase C yielded a transparent gel, whereas unphosphorylated fibrinogen yielded a coarse gel. The mass-length ratio was found to be one order of magnitude higher for the unphosphorylated than for the phosphorylated fibrinogen. Since the phosphorylated sites are located near the cross-linking sites in the A alpha-chain of fibrinogen, it is likely that the introduction of charged phosphate groups in this region prevent the lateral growth of the fibrin fibres.


Roles of pH in biologic production of hydrogen and volatile fatty acids from glucose by enriched anaerobic cultures.
Batch experiments were carried out to study the roles of pH in the biologic production of hydrogen and volatile fatty acids from glucose by enriched anaerobic cultures. The results showed that 95-99% of glucose in wastewater was acidified at 30 degrees C and pH 4.0-8.5. Hydrogen yield fluctuated between 1.30 and 1.57 mol of H2/mol of glucose when the reactor was operated at pH 4.0-5.0. However, a further increase in pH led to a considerable decrease in hydrogen yield, especially for the cases at pH 7.5 and 8.0. Acetate, propionate, butyrate, and ethanol were the key products of acidogenesis. Production of butyrate was favored at pH 4.0-5.0, whereas production of acetate was favored at pH 6.0-8.0. A modified Gompertz equation is able to properly describe the batch production of hydrogen from glucose. The optimum pH for the specific hydrogen production was found to be 5.5, close to 5.7, the optimum pH calculated using a semiempirical model.


The myorelaxant effect of theophylline on smooth muscle cells of the afferent arterioles and glomerular tuft.
Theophylline, infused i.v. into rats increased the diameter of the glomerular afferent arterioles by 35.78%; when added to a suspension of isolated glomeruli, it increased the diameter of the capillary tuft within the glomerulus by 25-30%. These variations in diameter can be explained by the myorelaxant effect of theophylline on the smooth contractile fibers present in the arteriolar cells and in certain glomerular cells, such as the mesangial cells. These observations explain, in part, the marked changes in glomerular hemodynamics caused by the injection of theophylline.


Evaluation of one-year effectiveness of clobazam as an add-on therapy to anticonvulsant monotherapy in participants with epilepsy having uncontrolled seizure episodes: An Indian experience.
To prospectively study the effectiveness and safety of clobazam as an add-on therapy in patients with epilepsy whose seizures are not adequately controlled with antiseizure medicine (ASM) monotherapy. We conducted a prospective, observational study at 28 neurology outpatient clinics in India from June 2017 to October 2019. Consecutive patients with epilepsy (older than 3 years) with inadequate seizure control with ASM monotherapy were initiated on clobazam. Patients were followed up at 1, 3, 6, 9, and 12 months. Seizure control and adverse events were assessed through personal interviews and seizure diaries. Out of 475 eligible patients, data of 429 patients (men: 65.5%) were evaluated (46 excluded due to protocol deviations). The median age was 25 (range, 3-80 years) years and the median duration of epilepsy was 3 (0.1-30) years. The majority of patients had focal epilepsy (55.0%) and genetic generalized epilepsy (40.1%). The one-year follow-up was completed by 380 (88.5%) patients. At one-year follow-up, 317 (83.4%; N = 380) patients in the study remained seizure free. These 317 patients who were seizure free at 12 months comprised 73.9% of the evaluable population (N = 429). In 98.8% of patients, the primary reason for adding clobazam was inadequate control of seizures with treatment. During one-year follow-up, a total of 113 (22.6%) patients experienced at least one adverse event which included 103 (20.6%) patients who experienced 386 episodes of seizures. The study provides preliminary evidence that clobazam is effective and well-tolerated as add-on therapy for a period of one year among patients with epilepsy inadequately stabilized with monotherapy. CTRI/2017/12/010906.


Exploring barriers to primary care for patients with severe mental illness: frontline patient and provider accounts.
The goal of this study was to obtain in-depth descriptions of barriers to primary care for adults with serious mental illness (SMI) and to provide solutions to these barriers. Qualitative interviews were administered to mental health and medical providers, as well as patients. Several major themes were reported including: poor access to care; patient limitations (e.g., psychopathology, cognitive difficulties); societal, health care system, and provider bias; integrated/fragmented care, communication difficulties; and quality of care issues. Results point to a need for nursing professionals to continue to improve access to medical care for this population, as well as to continue to integrate mental health and primary care.


Low-Intensity vs High-Intensity Home-Based Treadmill Training and Walking Attainment in Young Children With Spastic Diplegic Cerebral Palsy.
To compare the effect of low-intensity (LI) vs high-intensity (HI) treadmill training (TT) on walking attainment and overall walking activity in children with cerebral palsy (CP). Prospective, multisite, randomized controlled trial. Homes of the participants. Children with spastic diplegic CP, Gross Motor Function Classification System Level I and II, ages 14-32 months (N=19; male, n=8). The children were randomized to LI TT (2×/wk for 6wk) (n=10) and HI TT (10×/wk for 6wk) (n=9). The TT was carried out by the families with weekly instruction by the researchers. Children were assessed at study onset, post intervention, and 1 and 4 months post intervention with the Gross Motor Function Measure Dimension D/E (GMFM D/E), average strides per day and percentage of time spent walking with accelerometers, the Peabody Developmental Motor Scales-2 (PDMS-2), Pediatric Evaluation of Disability Index Mobility Scale, timed 10-m and 1-minute walk test, and Functional Mobility Scale. Blinding was conducted for GMFM D/E and PDMS-2. Linear mixed effects regression models were applied to all outcomes. No significant between-group differences were found in any outcome measure at any of the time points. Children in the HI group did not show significant improvement immediately following the intervention in GMFM E (P=.061), while children in the LI group did (P=.003), but no statistically significant differences were detected over time (P=.71). Children in the HI group showed better walking independence on the Functional Mobility Scale at all postintervention assessments. A twice-weekly dosage was equally effective in improving skills related to walking compared with a 10×/wk program and can be more readily implemented into clinical practice.


Evaluation of the effectiveness of iodine prophylaxis in Poland based on over 20 years of observations of iodine supply in school-aged children in the central region of the country.
Due to the mild-to-moderate iodine deficiency in Poland, in 1997 iodine prophylaxis based on obligatory salt iodization was introduced. We attempted to evaluate the effectiveness of such prophylaxis, based on over 20 years of observations of iodine supply in school-aged children in Opoczno district (Central Poland). A group of 603 children (316 girls and 287 boys), aged 6-14, was examined at 4 time points: in the years 1994, 1999, 2010 and 2016. The children were tested for urine iodine concentration (UIC) and in each child the thyroid volume was measured ultrasonographically. The median UIC in 1994 (45.5 μg/l) indicated moderate iodine deficiency, while after introducing prophylaxis it corresponded to adequate values (1999 - 101.1 μg/l, 2010 - 100.6 μg/l, 2016 - 288.3 μg/l); however, the last value was higher than the previous two. The thyroid size, assessed by ultrasonography and presented as volume/body surface area (V/BSA), in 1994 was 6.55 × 10-6 m; this value was higher than at other time points (2.73 × 10-6 m in 1999, 2.73 × 10-6 m in 2010, and 2.70 × 10-6 m in 2016). Iodine prophylaxis has proved effective in eliminating iodine deficiency. In recent years, the diversification of iodine sources, despite the reduction of salt consumption, has led to an increase in median UIC to values close to the upper limit of UIC, accepted as normal. Further increase in iodine supply may be unfavourable for health; therefore constant monitoring of iodine prophylaxis is required.


Endoscopic laryngo-pharyngeal surgery for elderly patients.
Due to the rising number of elderly patients and advances in endoscopic devices, early laryngeal and pharyngeal cancers are increasingly found in elderly patients. In these cases, minimally invasive endoscopic larygo-pharyngeal surgery (ELPS) may be indicated. However, the safety and efficacy of ELPS in elderly populations has not been established. The purpose of this study was to investigate the safety, outcomes and feasibility of ELPS in very elderly patients. Between February 2010 and April 2016, 29 pharyngeal cancerous or pre-cancerous lesions in 19 patients aged 75 years or older were treated with ELPS. Twenty-six resections were performed in total, and the patients' clinical courses were reviewed. Sixteen patients had multiple comorbidities and moderate to severe comorbidities were observed in 17 patients. The average surgical time and hospitalization period was 54.3min and 18.8 days, respectively. On average, oral intake began 4.4days after the procedure, and all patients eventually received nourishment by mouth; no percutaneous endoscopic gastrostomy dependency was observed. Complications included post-operative bleeding and aspiration pneumonia in two cases each, and all complications were safely managed. The 3-year overall survival rate was 90.2% and the 3-year disease-specific survival rate was 100%. ELPS was safely performed in elderly patients, suggesting that it is a feasible treatment option for pharyngeal lesions in very elderly patients.


A peptide derived from phage-display limits psoriasis-like lesions in mice.
Psoriasis is a pro-inflammatory disease with unknown etiology, that is characterized by skin inflammation and keratinocytes hyperproliferation. Specific inhibition of inflammation has shown positive effects avoiding the progression of the psoriatic lesions in different animal models of the disease, turning this strategy as a remarkable therapeutic alternative. To screen the effectiveness of a novel IFN-α/β signalling inhibitor in the development reduction of skin lesions in IMQ and TPA mice models of psoriasis. We used a Phage-peptide library for the screening of a peptide with inhibitory effects on the development of psoriasis-like lesions in mice. To evaluate the in vivo effect of the phage-peptides (Phpep3D) and the derived peptide (Pep3D), we administered Phpep3D or Pep3D intradermally in mice with imiquimod (IMQ)-induced psoriasis and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced psoriasis. We scored the lesions, and we determined the number of neutrophils and the production of some pro-inflammatory cytokines in the lesions. In this work, we describe how the Ph3pepD and Pep3D reduced skin thickness, redness, and acanthosis despite the presence of the psoriasis inducers, IMQ or TPA. We also found that Pep3D reduced the number of GR1+ infiltrated cells and decreased the production of IL-17A and TNFα in the psoriatic skin of mice. In-silico, docking analysis showed that Pep3D may interact with the interferon-alpha receptor, but further analyses should be performed to uncover the mechanism of action of this peptide. Our results suggest that Pep3D could be used as a new treatment for psoriasis.


Multicenter External Validation of the Deep Pelvic Endometriosis Index Magnetic Resonance Imaging Score.
Preoperative mapping of deep pelvic endometriosis (DPE) is crucial as surgery can be complex and the quality of preoperative information is key. To evaluate the Deep Pelvic Endometriosis Index (dPEI) magnetic resonance imaging (MRI) score in a multicenter cohort. In this cohort study, the surgical databases of 7 French referral centers were retrospectively queried for women who underwent surgery and preoperative MRI for DPE between January 1, 2019, and December 31, 2020. Data were analyzed in October 2022. Magnetic resonance imaging scans were reviewed using a dedicated lexicon and classified according to the dPEI score. Operating time, hospital stay, Clavien-Dindo-graded postoperative complications, and presence of de novo voiding dysfunction. The final cohort consisted of 605 women (mean age, 33.3; 95% CI, 32.7-33.8 years). A mild dPEI score was reported in 61.2% (370) of the women, moderate in 25.8% (156), and severe in 13.1% (79). Central endometriosis was described in 93.2% (564) of the women and lateral endometriosis in 31.2% (189). Lateral endometriosis was more frequent in severe (98.7%) vs moderate (48.7%) disease and in moderate vs mild (6.7%) disease according to the dPEI (P < .001). Median operating time (211 minutes) and hospital stay (6 days) were longer in severe DPE than in moderate DPE (operating time, 150 minutes; hospital stay 4 days; P < .001), and in moderate than in mild DPE (operating time; 110 minutes; hospital stay, 3 days; P < .001). Patients with severe disease were 3.6 times more likely to experience severe complications than patients with mild or moderate disease (odds ratio [OR], 3.6; 95% CI, 1.4-8.9; P = .004). They were also more likely to experience postoperative voiding dysfunction (OR, 3.5; 95% CI, 1.6-7.6; P = .001). Interobserver agreement between senior and junior readers was good (κ = 0.76; 95% CI, 0.65-0.86). The findings of this study suggest the ability of the dPEI to predict operating time, hospital stay, postoperative complications, and de novo postoperative voiding dysfunction in a multicenter cohort. The dPEI may help clinicians to better anticipate the extent of DPE and improve clinical management and patient counseling.


Maternal vs paternal diabetes: The parental history is different in younger onset versus older onset type 2 diabetes.
A number of previous studies exploring family history of type 2 diabetes have reported a predominance of maternal diabetes. These studies have not explicitly compared parental history of diabetes across the spectrum of disease onset from youth to later adulthood. Family history data from 11,467 patients with type 2 diabetes were extracted from the RPA Diabetes Centre database. Parental histories of diabetes were compared across a range of age of diagnosis strata (15-<30, 30-<40, 40-<50, 50-<60 and 60-<70 years). For the young-onset group (diagnosed between 15 and 30 years of age), associations between parental history of diabetes and the presence of cardio-metabolic risk factors and diabetic complications were also explored. For the total cohort and within each age of diagnosis strata, more individuals reported maternal history than paternal history of diabetes. The young-onset group demonstrated the highest prevalence of any parental history of diabetes (60.7%), the highest combined maternal and paternal history (15.8%) and the smallest differential between maternal (25.1%) and paternal (19.7%) history of diabetes. Within the young-onset group, no significant association between parental history and cardio-metabolic risk factors or diabetic complications were identified after a median of 15.0 years of diabetes exposure. Overall, our results demonstrate a consistent maternal excess of diabetes which could be consistent with an underlying epigenetic effect. However, the differential between maternal and paternal history is significantly lower in the young-onset group. Earlier emergence of type 2 diabetes may therefore reflect a different interaction and impact of genetic and environmental factors.


Female sex hormones and platelet/endothelial cell interactions.
The effects of estradiol and progesterone added to the growth medium of human umbilical vein endothelial cells for 72 h on the formation and release of prostacyclin were investigated. The influence on collagen-induced platelet aggregation and on the platelet formation of thromboxane A2 following aggregation, of the growth medium collected before and after thrombin stimulation of the endothelial cells, was studied simultaneously. Under basal conditions, endothelial cells grown with progesterone released significantly less prostacyclin into the growth medium than did controls (p less than 0.05). Following thrombin stimulation, endothelial cells grown with estradiol (p less than 0.05) or a combination of estradiol and progesterone (p less than 0.01) contained significantly less prostacyclin than controls. No significant effects on the platelet aggregation or platelet thromboxane formation could be found. This study indicates a lowering effect of both female sex hormones on the endothelial cell prostacyclin formation and release. This may be of significance for the increased risk of vascular disease in pregnant women and oral contraceptive users, but can hardly explain the consequences of the hormonal loss occurring at the menopause.


Preliminary evaluation of growth and conformation traits of local goats and Nubians upgraded by a black Boer line in Taiwan.
The goal of this research, conducted in the most southern part of Taiwan, was to create a new genotype: the "Hengchun Black Goat" (HB). Nubian (NU) goats were first crossed with a local breed, the Taiwan native (TN), then the F1 females were crossed with the imported black Boer (BO) bucks. The upgraded genotypes were then compared with the parental breeds and Kinmen (KM), another local breed, for growth traits and body conformation. The study concerned 1,136 kids born between 2005 and 2007. The analysed traits were body weight (BW), average daily gain and three linear measurements, namely height at withers, body length and chest girth. The results indicated that environmental factors, sex, birth and rearing type, dam parity and birth year had significant effects from birth to 6 months of age. The same differences persisted to 1 year. At 6 months of age, the least square means of BW were 16.2, 19.2, 25.1, 32.0, 23.9, 23.8, 23.0 and 23.9 kg, for KM, TN, NU, 1/2BO, 3/4BO, 7/8BO, BO and HB, respectively. These first results also indicate that the growth performances of the newly created line, Hengchun Black, were equivalent to those of Boer goats.


Imaging Mitosis with Lattice LightSheet.
Mitosis is one of the most fundamental processes of life, allowing organisms to grow, develop, and evolve. Acquiring microscopic images and understanding the detailed mechanism of this process is critical in the fields of cell and developmental biology. Modern fluorescence microscopy is the standard for imaging specific molecules and proteins as they interact during this complicated process. However, researchers must take care to ensure that they are maintaining the basal cell processes during mitosis without disruption by placing the sample on a microscope. In addition, mitosis in itself is an incredibly dynamic process that requires both high-speed and high-resolution imaging (McIntosh and Hays. Biology. 5:55, 2016). The Lattice LightSheet is an advanced system, developed in the lab of Eric Betzig (Chen et al. Science. 346:1257998), that offers imaging speeds in the volumes/second while still resolving fine, intracellular structures. Here we describe how to prepare cell culture samples for ideal mitotic imaging on this cutting-edge light sheet fluorescence microscope.


Gender and HIV risk behavior among intravenous drug users in Sichuan Province, China.
Using data from a community-based study of injection drug users (IDUs) in Sichuan Province in China, this study compared the level of HIV risk behavior (needle sharing and unsafe sex) amongst female and male IDUs, and examined the risk factors separately for these two groups. Five risk factors were examined in the analysis, including a lack of family support, having an IDU primary sex partner, economic pressure, lack of access to a methadone program, and younger age. Regression results showed that male and female IDUs had different risk factors. For male IDUs, younger age and a lack of family support increased their level of HIV risk behavior. For female IDUs, having an IDU primary sex partner and economic pressure were predictive of their HIV risk behavior. Sex differences in risk factors are explained with respect to gender norms surrounding HIV risk behavior in the context of social relations. Female IDUs who were sex workers suffered additional HIV risk due to their powerlessness in negotiating safe sex with male customers. Practical implications of the findings for HIV/AIDS prevention and intervention work in China are discussed.


Intracellular and intramitochondrial binding of lanthanum in dark degenerating midgut cells of a collembolan (insect).
Lanthanum is known to be a marker of extracellular spaces. Intracellular organelles are always devoid of stain. But dark and damaged cells may be entered by the marker, as studied at the cellular level, using the electron probe X-ray microanalyser. The technique may be used to detect increased permeability at a stage when no fine structural abnormality is discernible.


Oxygen activation and defence against oxygen toxicity in a psychrophilic Bacteroidaceae.
When suddenly exposed to air the growth of the obligate anaerobic bacterium of the bacteroidaceae type, strain B6, continues for a few hours before coming to a complete stop. When air is shut off soon after growth has ceased, the organism is able to reestablish anaerobic conditions due to an ability to reduce O2, and resumes normal growth after another few hours. The O2 reducing ability of the organism is due to the presence in the cells of a particle-bound NADH oxidase, a soluble NADPH oxidase and a soluble pyruvate oxidase. The two pyridine nucleotide oxidases reduce O2 to H2O2, the pyruvate oxidase reduces O2 to H2O. Catalase and peroxidase were not detected in anaerobically grown cells. Kinetic studies with cell-free extracts showed that the pyruvate oxidase had a considerably greater affinity (smaller Km) for O2 and capacity (higher Vmax) for O2 reduction than the two other oxidases. It is postulated that the pyruvate oxidase acts as a scavenger for O2, leading to the non-toxic reduction product H2O, and thus functions as a defense mechanism against oxygen toxicity when the organism is exposed to aerobic condition.


A systematic review of Tuina for women with primary dysmenorrhea: A protocol for systematic review and meta-analysis.
Primary dysmenorrhea (PD) occurs most often in adolescent girls. Tuina, a kind of Chinese massage, can effectively relieve women's pain and is widely used in clinical practice. However, there is no relevant systematic review show its effectiveness and safety. The study aims to assess the effectiveness and safety of Tuina for PD. The following electronic databases will be searched from the respective dates of database inception to September 1st, 2021: The Cochrane Library, Web of Science, EMBASE, Springer, MEDLINE, China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the World Health Organization International Clinical Trials Registry Platform, the Chinese Scientific Journal Database, Wanfang database, and other sources. This study will provide a high quality comprehensive and/or descriptive analysis of existing evidence on Tuina therapy for PD. This study will provide the evidence of whether Tuina is an effective and safe intervention for women with PD. CRD42021257392.


Characterization of the cellulolytic bacteria communities along the gastrointestinal tract of Chinese Mongolian sheep by using PCR-DGGE and real-time PCR analysis.
A balanced gastrointestinal microbial ecosystem is crucial for the health and growth of animals. In the gastrointestinal tract (GIT) of ruminants, cellulolytic bacteria aid in the digestion and absorption of nutrients. Rumen contents and feces in ruminants are often used to assess gastrointestinal microbial communities; however, these sites do not guarantee to represent the diversity of microbes found in the entire GIT. In this study, we investigated the microbiota along the GIT of five Chinese Mongolian sheep using PCR-denaturing gradient gel electrophoresis (DGGE) and real-time PCR analysis. Results indicated that microbiota were more abundant in the stomach and large intestine than in the small intestine. DGGE and real-time PCR revealed the predominance of Firmicutes and Bacteroidetes in the GIT. Meanwhile, Ruminococcus flavefaciens and Clostridium cluster IV showed significant difference in their abundance along the GIT (P < 0.05). Fibrobacter succinogenes was the most dominant species, followed by Ruminococcus albus and R. flavefaciens. The ileum harbored a larger number of cellulolytic bacteria, particularly-Clostridium cluster IV, than reported previously. In addition, comparisons between microbiota in the rumen and rectum indicated similar number of total bacteria, Firmicutes, Bacteroidetes, F. succinogenes, Butyrivibrio fibrisolvens, Clostridium cluster IV, and Clostridium cluster XIVa, whereas the number of R. albus and R. flavefaciens was higher in the rumen. This study investigated the composition and quantification of GIT microbial community in Chinese Mongolian sheep, and revealed for the first time the cellulolytic bacterial community in these sheep.


MGMT promoter methylation in gliomas-assessment by pyrosequencing and quantitative methylation-specific PCR.
Methylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter is a favorable prognostic factor in glioblastoma patients. However, reported methylation frequencies vary significantly partly due to lack of consensus in the choice of analytical method. We examined 35 low- and 99 high-grade gliomas using quantitative methylation specific PCR (qMSP) and pyrosequencing. Gene expression level of MGMT was analyzed by RT-PCR. When examined by qMSP, 26% of low-grade and 37% of high-grade gliomas were found to be methylated, whereas 97% of low-grade and 55% of high-grade gliomas were found methylated by pyrosequencing. The average MGMT gene expression level was significantly lower in the group of patients with a methylated promoter independent of method used for methylation detection. Primary glioblastoma patients with a methylated MGMT promoter (as evaluated by both methylation detection methods) had approximately 5 months longer median survival compared to patients with an unmethylated promoter (log-rank test; pyrosequencing P = .02, qMSP P = .06). One third of the analyzed samples had conflicting methylation results when comparing the data from the qMSP and pyrosequencing. The overall survival analysis shows that these patients have an intermediate prognosis between the groups with concordant MGMT promoter methylation results when comparing the two methods. In our opinion, MGMT promoter methylation analysis gives sufficient prognostic information to merit its inclusion in the standard management of patients with high-grade gliomas, and in this study pyrosequencing came across as the better analytical method.


Extraction and replacement of permanent pacemaker leads through occluded vessels: use of extraction sheaths as conduits--balloon venoplasty as an adjunct.
Patients (pts) may present for lead extraction with symptomatic or asymptomatic subclavian vein or superior vena cava thrombosis. Replacement of permanent pacemaker leads (PPLs) in these pts may be difficult and may require accessing a new site. We examined the utility of replacing PPLs through completely occluded vessels using extraction sheaths as conduits through the total occlusion. Over six years, a total of 210 atrial and/or ventricular PPLs were extracted from 137 pts. Two pts presented with angiographically documented thrombotic occlusion of the subclavian vein. One additional pt. who had presented with a superior vena cava (SVC) syndrome, had a totally occluded innominate vein and SVC occlusion. Balloon venoplasty was used as an adjunct to dilate the SVC. In all pts, after PPLs were removed via a subclavian extraction sheath through the occluded vessel, the retained sheath was used to place a guide wire, then a peel away dilating sheath, to insert new PPLs, in each case on the side of total venous occlusion. Seven PPLs and two lead fragments were extracted, and five new PPLs replaced, ipsilateral to the venous occlusion. These data show that extraction of PPLs through thrombosed veins may be performed successfully and may not require replacing the leads through a new site. This technique spares the pt the need to access the opposite subclavian vein, and it avoids an excessive number of PPLs in the subclavian vein and SVC. The procedure illustrates an efficient means to reintroduce new PPLs with the potential to reduce associated morbidity, since repeat puncture of the subclavian vein is not required. Safety of the procedure as a whole must be considered with regard to the known risks of lead extraction, some complications of which may be substantial using current techniques.


Nutrition in Chronic Liver Disease.
Malnutrition is a common finding in patients with chronic advanced liver disease (CLD) and is an important prognostic predictor for morbidity and mortality. This review aims to summarize the latest evidence-based guidelines and expert opinion regarding diagnosing malnutrition in patients with CLD and providing optimal solutions. In addition to diet, evidence demonstrates sarcopenia and frailty are emerging concepts critical to outcomes in those with CLD. Thus, adequate assessment of nutritional status incorporates the interplay of nutrient intake, sarcopenia, and frailty. Addressing malnutrition in patients with CLD requires understanding the multifactorial mechanisms contributing to nutritional deficiencies, but also careful assessment of functional capacity. Interventions mitigating or reversing sarcopenia and frailty are equally important to nutritional supplementation. While the latency period between compensated and decompensated cirrhosis provides a good window for fruitful interventions, we believe providers need to be vigilant early on the course of CLD to maximize nutritional gains and halt muscle loss.


Parathyroid function in Paget's disease of bone.
In order to determine the prevalence of secondary hyperparathyroidism in patients with Paget's disease of bone, we measured serum parathyroid hormone levels (N-terminal assay) in 39 patients with a wide range of pagetic activity. All patients had normal serum calcium levels. A total of 30 patients were either untreated or had received no treatment for 6 months or longer when studied; the other 9 were receiving either salmon calcitonin (3) or EHDP (6). The results showed that in 7 of the 39 patients (18%) parathyroid hormone levels were increased above normal. These were among the most severely affected cases, as manifested by the degree of elevation of three pagetic biochemical indices: serum alkaline phosphatase, plasma bone Gla protein, and 24 h urinary hydroxyproline-creatinine ratios. Levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 were normal. We examined the relationships between parathyroid hormone and each of the three pagetic indices as well as serum calcium for the entire group of 39 patients. Parathyroid hormone values did not correlate with serum calcium measurements (r = -0.241, p = NS) but did correlate significantly with serum alkaline phosphatase (r = 0.496, p less than 0.001), plasma bone Gla protein (r = 0.537, p less than 0.001), and urinary hydroxyproline (r = 0.450, p less than 0.011). We conclude that relative or absolute increases in parathyroid hormone may occur in moderately active Paget's disease, possibly in the setting of greater calcium demands during periods of increased pagetic new bone formation.(ABSTRACT TRUNCATED AT 250 WORDS)


The sun and water sports.
Participation in aquatic sports such as sailing, fishing, SCUBA diving, and windsurfing often entails the unavoidable hazard of exposure to high levels of solar radiation. This review discusses what is known about the health hazards of ultraviolet radiation and presents information that allows a rational approach to sun protection.


Preoperative Valsalva leak point pressure may not predict outcome of mid-urethral slings. Analysis from a randomized controlled trial of retropubic versus transobturator mid-urethral slings.
To test the hypothesis that preoperative Valsalva leak point pressure (VLPP) predicts long-term outcome of mid-urethra slings for female stress urinary incontinence (SUI). One hundred and forty-five patients with SUI were prospectively randomized to two mid-urethra sling treatments: Tension free vaginal tape (TVT) or transobturator tape (TOT). They were followed-up at 3, 6, 12 months post-operatively and then annually for the primary outcome variable, i.e. dry or wet and secondary outcome variables such as scores on the urogenital distress inventory (UDI-6) and the impact of incontinence on quality of life (IIQ-7) questionnaire as well as patient satisfaction as scored on a visual analogue scale (VAS). Preoperative VLPP was correlated with primary and secondary outcome variables. Mean follow-ups were 32 +/- 12 months (range 12-55) for TVT and 31 +/- 15 months (range 12-61) for TOT. When patients were analyzed according to VLPP stratification, 95 (65.5%) patients showed a VLPP > 60 cm H2O and 50 (34.5%) patients had a VLPP < or = 60 cm H2O. The overall objective cure rates were 75.8% for patients with VLPP > 60 cm H2O and 72% for those with VLPP < or = 60 cm H2O (p < 0.619). No significant differences in objective cure rates emerged when patients were stratified for pre-operative VLPP and matched for TOT or TVT procedures: VLPP > 60 cm H2O (82% vs. 68.9% p < 0.172); VLPP < or = 60 cm H2O (68% vs. 76% p < 0.528). When patients were stratified for preoperative VLPP (< or = or > of 60 cm H2O), preoperative VLPP was not linked to outcome after TVT or TOT procedures.


In vitro activity of azithromycin and tetracycline against 358 clinical isolates of Brucella melitensis.
The in vitro activity of azithromycin against human pathogenic strains of Brucella melitensis was tested at three centres and compared to that of tetracycline, the standard antibiotic currently used for the treatment of human brucellosis. MIC determination was carried out. Tested concentration ranges for both azithromycin and tetracycline were between 0.03 and 16 micrograms/ml. Brucella melitensis biotype 1, strain M16 was employed as a control microorganism. A total of 358 Brucella melitensis strains from human blood cultures were tested. MIC90 (micrograms/ml) values ranged from 0.5 to 1.00 for azithromycin and were 0.25 for tetracycline. It was concluded that there was little difference in the sensitivity of pathogenic Brucella melitensis to azithromycin and tetracycline isolated from three different regions in Spain. These results encourage further investigations on the possible therapeutic role of azithromycin in brucellosis.


Pediatric ulcerative colitis: three- versus two-stage colectomy with ileal pouch-anal anastomosis.
Despite advancements in medical therapy for ulcerative colitis (UC), a significant proportion of children progress to colectomy with ileal pouch-anal anastomosis (IPAA). Procedural related complications between two- and three-stage operations in children have not been well described. We performed a retrospective review of patients who underwent a colectomy for UC or inflammatory bowel disease unclassified between 2008 and 2018. Forty-nine children underwent an IPAA at the time of colectomy (two stage) or during a subsequent operation (three stage). Preoperative hemoglobin and albumin concentrations were lower among those undergoing three-stage procedures. The rate of early complications (≤30 days) was similar between the two groups (p = 0.46); however, late complications (>30 days) were more commonly associated with three-stage procedures (p = 0.03). Time with a stoma was 3.2 months longer among those who underwent a three-stage procedure. While three-stage procedures were more often performed during the first half of the study period (2008-2012), two-stage procedures became more common during the second half (2013-2018). During this transition to favor two-stage procedures, complication rates did not significantly change. Although three-stage procedures were thought to be associated with fewer complications, we found comparable complication rates as we transition to two-stage procedures.


Crystal structures of (S)-(+)-5-(3-bromo/chloro-4-isopropoxyphen-yl)-5-methyl-imidazolidine-2,4-dione.
In (S)-(+)-5-(3-bromo-4-isopropoxyphen-yl)-5-methyl-imidazolidine-2,4-dione, C13H15BrN2O3, (I), the hydantoin groups are connected via inter-molecular N-H⋯O hydrogen bonds, forming a terraced sheet structure. In the chloro analogue, (S)-(+)-5-(3-chloro-4-isopropoxyphen-yl)-5-methyl-imidazolidine-2,4-dione, C13H15ClN2O3, (II), the inter-molecular N-H⋯O hydrogen-bonding network forms a flat sheet. Comparison of the crystal structures reveals that (II) is more loosely packed than (I).


Target dependent femtosecond laser plasma implantation dynamics in enabling silica for high density erbium doping.
Chemical dissimilarity of tellurium oxide with silica glass increases phase separation and crystallization tendency when mixed and melted for making a glass. We report a novel technique for incorporating an Er(3+)-doped tellurite glass composition into silica substrates through a femtosecond (fs) laser generated plasma assisted process. The engineered material consequently exhibits the spectroscopic properties of Er(3+)-ions, which are unachievable in pure silica and implies this as an ideal material for integrated photonics platforms. Formation of a well-defined metastable and homogeneous glass structure with Er(3+)-ions in a silica network, modified with tellurite has been characterized using high-resolution cross-sectional transmission electron microscopy (HRTEM). The chemical and structural analyses using HRTEM, Rutherford backscattering spectrometry (RBS) and laser excitation techniques, confirm that such fs-laser plasma implanted glasses may be engineered for significantly higher concentration of Er(3+)-ions without clustering, validated by the record high lifetime-density product 0.96 × 10(19) s.cm(-3). Characterization of planar optical layers and photoluminescence emission spectra were undertaken to determine their thickness, refractive indices and photoluminescence properties, as a function of Er(3+) concentration via different target glasses. The increased Er(3+) content in the target glass enhance the refractive index and photoluminescence intensity of the modified silica layer whilst the lifetime and thickness decrease.


The passive recipient: Neural correlates of negative self-view in depression.
Previous studies have argued that people tend to isolate themselves from negative information. This tendency is modulated by the individual's role in social interaction, that is, as an initiative actor (e.g., "I hit Tom") or a passive recipient (e.g., "Paul hits me"). Depressed patients tend to focus on negative aspects of themselves and cope with situations passively. It is still an open question how the actor/recipient role affects the behavioral and neural responses to self in depression. The present study adopted functional magnetic resonance imaging (fMRI) technology to investigate behavioral and neural responses to self (as an actor/recipient) in depressed patients and the matched healthy controls when attributing negative events. Compared with healthy controls, depressed patients showed more self-attribution for negative events. Depressed patients showed increased brain activity in the dorsal medial prefrontal cortex (dmPFC) subsystem of the default mode network (DMN) when they played recipient role in self-related negative events. Activity of the dmPFC subsystem was negatively correlated with depressed patients' self-attribution for negative events in recipient condition. While decreased brain activity in the medial temporal lobe (MTL) subsystem was observed in depressed patients when they played the actor or recipient role in self-related negative events. Activity of the MTL subsystem was negatively correlated with depressed patients' reaction time when they played recipient role in selfrelated negative events. These results implicated that depressed patients manifested the negative self-view. Actor/recipient role affected their activation patterns in the DMN which were different from the healthy controls. The correlation between the abnormal brain activations of the DMN and the behavioral performances might manifest more easily when depressed patients played recipient role in negative events.


Calmodulin stimulation and calcium regulation of smooth muscle adenylate cyclase activity.
The Ca2+-dependent regulation of the adenylate cyclase activity associated with microsomes isolated from bovine aortic smooth muscle has been studied. Calmodulin content of microsomal membranes employed in these studies was 80 +/- 14 ng/mg as determined by specific radioimmunoassay. In the absence of exogenous calmodulin, Ca2+ concentrations greater than 0.8 microM inhibited adenylate cyclase activity with one-half-maximal inhibition occurring at 2.5 microM Ca2+. In the presence of 5 or 9 microM bovine testis calmodulin, Ca2+ stimulated smooth muscle adenylate cyclase activity with one-half-maximal stimulation occurring at 0.2 microM for both 5 and 9 microM calmodulin. Calmodulin stimulation was observed between 0.1 and 0.8 microM Ca2+. Despite the presence of calmodulin, Ca2+ concentrations greater than 0.8 microM were inhibitory to smooth muscle adenylate cyclase activity. However, calmodulin reduced the sensitivity of the enzyme to inhibition by Ca2+. Trifluoperazine (100 microM) reversed both the calmodulin-dependent stimulation of cyclase activity and the calmodulin-induced decrease in sensitivity to the inhibitory actions of Ca2+. Trifluoperazine alone shifted the curve describing Ca2+ inhibition of cyclase activity to the left. The value of Ca2+ for one-half-maximal inhibition decreased from 2.9 to 1.2 microM. The trifluoperazine-induced shift was reversed by exogenous calmodulin. These data suggest: 1) Ca2+, at physiological concentrations, can stimulate as well as inhibit smooth muscle adenylate cyclase activity; 2) the stimulation of adenylate cyclase activity is mediated by calmodulin; 3) the Ca2+-calmodulin complex reduces the sensitivity of smooth muscle adenylate cyclase to the inhibitory actions of Ca2+; and 4) the level of calmodulin associated with smooth muscle adenylate cyclase may modulate the response (both stimulatory and inhibitory) of the enzyme to Ca2+.


MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT.
We compared the diagnostic capabilities of MRI to CT, evoked potentials (EP), and CSF oligoclonal banding analysis in a prospective evaluation of 200 patients with suspected multiple sclerosis (MS). MRI was the best method for demonstrating dissemination in space. An abnormal appropriate EP in monosymptomatic disease was usually supported by MRI and CSF analysis as being predictive of MS as a clinical diagnosis. A normal appropriate EP study was not satisfactory because MRI and CSF analysis often did not support a diagnosis of non-MS. When there is agreement between three of these paraclinical studies, the diagnosis of MS is probably unequivocal. For use in research studies, laboratory-supported definite MS (LSDMS) could be diagnosed in 85 patients of the total 200 (42.5%), in 19/38 (50%) of optic neuritis (ON) patients, and in 24/52 (46%) of chronic progressive myelopathy (CPM) patients. MRI was 100% successful in identifying patients who qualified for LSDMS in the ON and CPM groups. In a short follow-up (less than 1 year), 19/200 (10%) went on to develop clinically definite MS (CDMS), and MRI predicted that diagnosis in 18/19 (95%). Only long-term follow-up will show how well these studies and the category of LSDMS predict the development of CDMS. The clinical diagnosis of MS (CDMS), even though only 95% accurate, must remain the gold standard.