Impact of lymphadenectomy in patients with locally recurrent or persistent cervical cancer treated with salvage hysterectomy.
To investigate the role of lymphadenectomy (LND) in locally recurrent or persistent cervical cancer patients treated with salvage hysterectomy. Locally recurrent or persistent cervical cancer patients treated with salvage hysterectomy, with or without LND, were identified. Patients were divided into two groups according to the status of radiologic evidence of lymph node metastasis, and the impact of LND was investigated by evaluating postoperative survival. This study included 72 patients; 48 did not show radiological evidence of lymph node metastasis (Group 1) while 24 did (Group 2). Overall, the addition of LND to salvage hysterectomy resulted in increased postoperative complications. In Group 1, salvage hysterectomy plus LND resulted in the identification of five cases with false-negative lymph nodes (19.2%), but showed no advantage over salvage hysterectomy alone in terms of postoperative survival. In Group 2, all patients underwent LND, which resulted in the identification of eight cases with false-positive nodes (33.3%), and reasonably long postoperative survival. The estimated 3-year postoperative survival rate in this group was 39.7%. Including LND in salvage hysterectomy allows for precise lymph node staging but increases risk of postoperative complications. However, considering the inability to improve survival, LND should not be performed during salvage hysterectomy in patients without radiological evidence of lymph node metastasis. In patients with radiological evidence of lymph node metastasis, salvage hysterectomy plus LND can only be performed in those who understand the risk of postoperative complications and the limited evidence supporting its survival advantage.


Recent advances in cellulose, pectin, carrageenan and alginate-based oral drug delivery systems.
Polymers-based drug delivery systems constitute one of the highly explored thrust areas in the field of the medicinal and pharmaceutical industries. In the past years, the properties of polymers have been modified in context to their solubility, release kinetics, targeted action site, absorption, and therapeutic efficacy. Despite the availability of diverse synthetic polymers for the bioavailability enhancement of drugs, the use of natural polymers is still highly recommended due to their easy availability, accessibility, and non-toxicity. The aim of the review is to provide the available literature of the last five years on oral drug delivery systems based on four natural polymers i.e., cellulose, pectin, carrageenan, and alginate in a concise and tabulated manner. In this review, most of the information is in tabulated form to provide easy accessibility to the reader. The data related to active pharmaceutical ingredients and supported components in different formulations of the mentioned polymers have been made available.


In vitro and in vivo interactions of cells with biomaterials.
The biocompatibility of materials at an implant site involves a complex interaction of cells and tissues with the biomaterial. This cell-cell and cell-polymer interaction evokes the release of mediators such as chemotactic and growth factors that elicit and sustain inflammatory responses at the implant site. In this review, we summarize the interaction of cells with biomaterials in vitro and in vivo.


Gastrin regulates ABCG2 to promote the migration, invasion and side populations in pancreatic cancer cells via activation of NF-κB signaling.
Gastrin is absent in most normal adult pancreatic tissues but is highly expressed in pancreatic cancer tissues. Although Gastrin expression was reported to be associated with tumor proliferation in human pancreatic cancer, studies on the relationship between Gastrin and tumor metastasis in pancreatic cancer are rare. In this study, we performed an analysis to determine the effects of Gastrin on modulating the side populations, cell proportion and tumor cell metastatic potential and invasion activity and explored its mechanisms in pancreatic cancer. We indicated that Gastrin and ABCG2 were widely expressed in pancreatic cancer cell lines and overexpressed in cancer tissues. Gastrin induced ABCG2 expression, and this effect was mediated by NF-κB activation. Gastrin regulated the SP proportion of BxPC-3 cells via modulating ABCG2 expression. Through the regulation of the functions of NF-κB/ABCG2, Gastrin functionally promoted the migration and invasion in pancreatic cancer cell. The present study indicated that Gastrin induced ABCG2 expression by activating NF-κB and thereby modulated the SP proportion, tumor cell metastatic potential and invasion activity in pancreatic cancer. Gastrin could serve as an effective therapeutic target for the metastasis of pancreatic cancer.


Isolation and amino-terminal sequence of a novel cellular growth inhibitor (inhibitory diffusible factor 45) secreted by 3T3 fibroblasts.
A growth inhibitory protein named inhibitory diffusible factor 45 (IDF45) has been purified to homogeneity from medium conditioned by dense cultures of mouse 3T3 cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of fast protein liquid chromatography-purified bioactive material showed a single band corresponding to a protein of 45 kDa. The molecule is a monomer. The pI of the molecule, as determined by isoelectric focusing, is about 6.5. The amino-terminal sequence of the protein was established as Ser-Ala-Gly-Ala-Val-Gly-Ala-Gly-Pro-Val-Val-Arg. The protein inhibits DNA synthesis in chicken embryo fibroblasts in a dose-dependent manner (ED50: 40 ng/ml, approximately 1 nM). The chemical properties of IDF45, i.e. molecular weight and amino-terminal sequence, clearly distinguish it from other known growth inhibitory proteins.


Impact of 2-Ethylhexyl Stereoisomers on the Electrical Performance of Single-Crystal Field-Effect Transistors.
Many organic semiconductors (OSCs) inherit chiral alkyl chains, which ensure the desirable high solubility for solution-processing but may also lead to disorder, inhomogeneous film-formation, as well as interfacial defects due to the presence of mixtures of stereoisomers or diastereomers, which impair their peak performance. Here, single-crystal field-effect transistors (SCFETs) of a diketopyrrolopyrrole-based organic semiconductor with chiral 2-ethylhexyl substituents by sublimation in air and organic ribbon mask method are fabricated. Devices of the mesomer (R/S), both enantiomers (R/R, S/S), as well as mixtures of these three stereoisomers measured under ambient conditions exhibit all appreciable p-channel charge carrier mobilities of > 0.1 cm2 V-1 s-1 despite different packing arrangement in the R/S, R/R (or S/S), and racemate crystal structures. These results suggest a surprising tolerance for isomeric impurities. The highest literature-reported p-channel mobility so far for a diketopyrrolopyrrole-based OSC of 3.4 cm2 V-1 s-1 (Ion /Ioff of 1 × 106 ) is, however, only obtained for the pure R/S mesomer, illustrating the inherent potential of stereochemical purity. These results on SCFETs are further substantiated by studies on organic thin-film transistors (OTFTs) of pure and mixed thin films of the different stereoisomers.


Does dihydroergotamine potentiate the thromboprophylactic effect of dextran 70? A controlled prospective study in general and hip surgery.
In a prospective randomized controlled study on postoperative thromboembolism, 259 patients undergoing elective general surgery, emergency general surgery, total hip replacement or hip fracture surgery were given thromboembolic prophylaxis with either a combination of dextran 70 and dihydroergotamine (DHE) or with dextran 70 alone. 500 ml dextran 70 was infused twice on the day of operation, once on postoperative days 1 and 3, and also on day 5 if the patient was still confined to bed. 0.5 mg DHE was given s.c. twice daily starting before operation and continued for 3 or 5 postoperative days. In hip fracture patients prophylaxis was started as soon as the diagnosis was made. 500 ml dextran 70 was given every other day before operation. DHE was given twice daily if so indicated from randomization. The patients were screened for deep-vein thrombosis (DVT) with the 125I-labelled fibrinogen test for 8 days and followed for one month postoperatively. In hip fracture surgery the incidence of DVT was significantly reduced by the combination of dextran 70 and DHE compared to dextran 70 alone (1/32 vs. 11/36, P = 0.003). However, this synergistic effect of DHE could not be detected in the other patient groups. Fatal pulmonary embolism did not occur. No severe side effects attributable to prophylaxis were noted in either group.


Application of assessment models for pollution and health risk from effluent discharge into a tropical stream: case study of Inyishi River, Southeastern Nigeria.
Pollution and health risk assessment models were used to study the effects of effluents discharged into the Inyishi River, Ikeduru LGA, Imo State, Nigeria. The study aims at investigating the environmental health effects of wastewater effluent discharge from the aluminum extrusion company on the Inyishi River. Samples were collected from both the aluminum extrusion company and Inyishi River and analyzed for physicochemical and trace metal parameters. Models adopted for assessment include transfer factor (TF), contamination factor (Cf), pollution load index (PLI), ecological risk factor (Er), water quality index (WQI), hazard quotient (HQ), and hazard index (HI). The results of the study revealed that pH and TH were within the Nigerian Standard for Drinking Water Quality (NSDWQ) and World Health Organization (WHO) standards. EC values at 2235 ± 0.001 and 105 ± 0.03 μS/cm for S3 and S4 respectively were higher than the permissible standards, while the values of EC at 24.04 ± 0.03, 5.26 ± 0.005, and 0.05 ± 0.01 μS/cm respectively for S1, S2, and SR are within the WHO standard. Very high concentration of SO42- was recorded at S3, while low concentration was measured at S2. Mean values of heavy metal ions studied were within NSDWQ and WHO standards for safe drinking water except for Al, Zn, Cd, Fe, and Mn, with the mean values of metal concentrations observed in the order Al > Fe > Zn > Mn > Cd > Cr. Positive linear correlation based on heavy metal contamination was observed for samples S1 and S2 with SR. High TF values were observed in decreasing order Mn > Cd > Cr > Fe > Zn. Similarly, very high CF was observed for Cd and Al while the PLI was generally high for all the samples. Low Er values were observed for all metals except for Cd, with the mean value of Er observed in the decreasing order Cd ˃ Mn ˃ Zn ˃ Cr. The river water sample generally revealed high WQI and was thus categorized as poor quality. HQ and HI values were below unity (< 1), but might pose health risk to children in cases of prolonged dermal adsorption. In conclusion, the quality of the Inyishi River has been negatively impacted by the wastewater effluent from the aluminum extrusion company. Proper treatment of the river water is therefore recommended before use for domestic purposes as prolonged usage of the untreated water might likely pose serious environmental health risks.


Multiple foreign non-H-2 determinants on the surface of a chemically-induced murine sarcoma.
By immunizing BALF/c (H-2d) mice against normal tissues from C57BL/6J (H-2d), C3Hf (H-2k) and DBA/2 (H-2d), but not from AKR (H-2k) strains, resistance was induced to the subsequent challenge of the 'syngeneic' methyl-cholanthrene-induced BALB/c sarcoma ST5; lymph node cells from alloimmune BALB/c mice were also able to exert a parallel cytotoxic effect against in vitro cultured ST5 cells. The involvement of foreign H-2 specificities in the observed cross-reactions was ruled out by absorption of H-2 monospecific sera and by the interallelic combinations used, thus suggesting that non-H-2 histocompatibility antigens were responsible for the above findings. By using the indirect isotopic antiglobulin assay, BALF/c anti-C57BL/6J and anti-C3Hf polyspecific sera were found to bind specifically to cultured ST5 cells. C57BL/6J and C3Hf, but not DBA/2, lymph node cells were able to absorb the anti-ST5 activity of the anti-C57BL/6J serum. These results indicated that ST5 cells expressed on their surface at least two different sets of foreign non-H-2 antigens: one shared by C57BL/6J and C3Hf tissues, and detected by both cell-mediated and serological techniques; the other one belonging to DBA/2 tissues, and revealed mainly at the cell-mediated level.


A chloroplast protein binds a viroid RNA in vivo and facilitates its hammerhead-mediated self-cleavage.
Viroids, small single-stranded circular RNAs (246-401 nucleotides), do not have mRNA capacity and must recruit host proteins to assist in the steps of their biological cycle. The nature of these cellular factors is poorly understood due to a lack of reliable experimental approaches. Here, to screen for host proteins interacting with viroid RNAs in vivo, we UV-irradiated avocado leaves infected with avocado sunblotch viroid (ASBVd), the type member of chloroplast viroids containing hammerhead ribozymes. This resulted in the detection of several ASBVd-host protein adducts. Tandem mass spectrometry analysis of the most abundant cross-linked species identified the protein component as two closely related chloroplast RNA-binding proteins (PARBP33 and PARBP35) of a family whose members previously have been shown to be involved in stabilization, maturation and editing of chloroplast transcripts. PARBP33 behaves as an RNA chaperone that stimulates in vitro the hammerhead-mediated self-cleavage of the multimeric ASBVd transcripts that result from rolling circle replication, indicating that this reaction, despite its RNA-based mechanism, is facilitated by proteins. The structural and functional parallelism between PARBP33 and PARBP35, and some proteins involved in viral RNA replication, indicates that viroids and RNA viruses recruit similar host proteins for their replication.


Marriage, motherhood and psychiatric morbidity in New Zealand.
The prevalence of psychiatric disorder, as assessed by both the GHQ-28 and the short PSE, is described for a random community sample of New Zealand women. In contrast to previous studies, married and widowed women and mothers showed lower rates than the never married and childless women. A plausible explanation is provided by available analysis of New Zealand gender roles. Such an explanation would reconfirm the importance of socio-cultural factors in community psychiatric disorder.


Type 2 diabetes in younger adults: clinical characteristics, diabetes-related complications and management of risk factors.
To describe the clinical characteristics and risk factors of adults <35 years with type 2 diabetes (T2DM). Observational study of 185 younger adults attending a specialist diabetes clinic. In this cohort 65% were female, 51% Caucasian, 43% South Asian. Characteristics at presentation: age 24 ± 5.5 years, BMI 33 ± 7.6 kg/m(2) and HbA1c 9.0% ± 2.3. Follow up of 3.2 ± 2.8 years with a diabetes duration of 4.5 ± 3.6 years. HbA1c had improved compared with diagnosis (8.3 ± 2.2% vs. 9.0% ± 2.3%, p<0.0001), but 63% still had an HbA1c>7%. Oral anti-diabetic drugs were used in 72%, insulin alone in 19% and both in 26%. 41% had a BP ≥ 140/80 mmHg, 78% total cholesterol >4 mmol/l, 63% LDL >2 mmol/l, 56% triglycerides >1.7 mmol/l. From diagnosis only the cholesterol and LDL improved significantly, with a modest increase in primary prevention therapy (statin 12-26%, p<0.0001, anti-hypertensives 16-29%, p<0.0001, aspirin 8-12%, p=0.18). 13% had retinopathy, 21% microalbuminuria. 46% had not been reviewed within the past year. This group represents an extreme phenotype with a high prevalence of insufficiently treated metabolic risk factors. There is need for tailored management strategies to engage and aggressively manage this high-risk group.


Evaluation of Terpenes' Degradation Rates by Rumen Fluid of Adapted and Non-adapted Animals.
The aim of the present study was to evaluate terpenes degradation rate in the rumen fluid from adapted and non-adapted animals. Four castrated healthy animals, two rams and two bucks, were used. Animals were daily orally dosed for 2 weeks with 1 g of each of the following terpenes, α-pinene, limonene and β-caryophyllene. At the end of each week, rumen fluid (RF) samples were assayed in vitro for their potential to degrade terpenes over time. For each animal, a 10 mL reaction medium (RM) at a ratio 1:9 (v/v) was prepared and a terpenes solution at a concentration of 100 μg/ml each, was added in each RM tube. Tubes were incubated at 39 °C under anaerobic conditions and their contents sampled at 0, 2, 4, 8, 21 and 24 h. RF could degrade terpenes as it was shown by the significantly (P < 0.05) higher overall degradation rates. Individual terpene degradation rates, were significantly (P < 0.05) higher in week 5 for limonene and marginally (P = 0.083) higher also in week 5 for α-pinene. In conclusion, the findings of the present preliminary study suggest that terpenes can be degraded in the rumen fluid.


Time resolved secretion of chloride from a monolayer of mucin-secreting epithelial cells.
Short-circuit current (Isc) measurement is used to quantify transepithelial ion flux. This technique provides a direct measure of net charge transport across a cell monolayer. Isc however, lacks chemical selectivity. Chemically resolved ion fluxes may be much greater than Isc, and differ in different biological processes. This work describes a novel experimental approach and deconvolution method to obtain temporally resolved ion fluxes at epithelial cell monolayers. HT29-Cl.16E cells, a sub clone of the human colonic cancer cell line HT29 was used as a model cell line to validate this approach in the context of epithelial transport studies. This cell line is known to secrete chloride in response to purinergic stimulation. Changes in chloride concentration after stimulation with 1 mM ATP plus 50 nM phorbol-myristate acetate (PMA) are recorded with a chloride ion-selective electrode (ISE) at a short distance (approximately 50 microm) from the monolayer. The recorded concentrations are transformed to corresponding chloride flux across the monolayer using a deconvolution algorithm for extracellular mass transport based on minimization of the shape error function (Nair and Gratzl in Anal Chem 77:2875-2888, 2005). Simultaneous voltage clamp yields the associated net electrical charge flux (Isc). The dynamics of Cl(-) flux did correlate with that of the electrical flux, but was found to be greater in amplitude. This suggests that Cl(-) may not be the only ion secreted. The method of simultaneously assessing ionic and electrical fluxes with a temporal resolution of seconds provides unique information about the dynamics of solute fluxes across the apical membrane.


How to Predict Parturition in Cattle? A Literature Review of Automatic Devices and Technologies for Remote Monitoring and Calving Prediction.
Cattle farming is facing an increase in number of animals that farmers must care for, together with decreasing time for observation of the single animal. Remote monitoring systems are needed in order to optimize workload and animal welfare. Where the presence of personnel is constant, for example in dairy farms with great number of lactating cows or with three milking/day, calving monitoring systems which send alerts during the prodromal stage of labor (stage I) could be beneficial. On the contrary, where the presence of farm personnel is not guaranteed, for example in smaller farms, systems which alert at the beginning of labor (stage II) could be preferred. In this case, time spent observing periparturient animals is reduced. The reliability of each calving alarm should also be considered: automatic sensors for body temperature and activity are characterized by a time interval of 6-12 h between the alarm and calving. Promising results have been shown by devices which could be placed within the vaginal canal, thus identifying the beginning of fetal expulsion and optimizing the timing of calving assistance. However, some cases of non-optimal local tolerability and cow welfare issues are reported. Future research should be aimed to improve Sensitivity (Se), Specificity (Sp) and Positive Predictive Value (PPV) of calving alert devices in order to decrease the number of false positive alarms and focusing on easy-to-apply, re-usable and well tolerated products.


Antibacterial and inducer activities for tetracycline resistance by its derivates and analogues.
Antibacterial and inducer activities of thirteen TC derivates were investigated for tetracycline (TC) resistance in staphylococcus aureus. Four compounds of the TC derivatives were not able to induce the resistance to TC in Staphylococcus aureus MS3937 rms7 (TC) + harboring an inducible TC resistance determinant located on a plasmid. The 12a-hydroxy position seems to be essential for the inducer activity.


High class filtering facepiece (FFP) are fundamental and effective in protection of emergency health care workers: an observational cohort study in a German community.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious airborne virus inducing pandemic coronavirus disease 2019 (COVID-19). This is most relevant for medical staff working under harmful conditions in emergencies often dealing with patients and an undefined SARS-CoV-2 status. We aimed to measure the effect of high-class filtering facepieces (FFP) in emergency medical service (EMS) staff by analyzing seroprevalence and history of positive polymerase chain reaction (PCR) for SARS-CoV-2. This observational cohort study included workers in EMS, who were compared with hospital staff (HS) and staff, which was not directly involved in patient care (NPC). All direct patient contacts of EMS workers were protected by FFP2/N95 (filtering face piece protection class 2/non-oil-based particulates filter efficiency 95%) masks, whereas HS was protected by FFP2/N95 exclusively when a patient had a proven or suspected SARS-CoV-2 infection. NPC was not protected by higher FFP. The seroprevalence of SARS-CoV-2 antibodies was analyzed by immunoassay by end of 12/2020 together with the history of a positive PCR. In addition, a self-assessment was performed regarding the quantity of SARS-CoV-2 positive contacts, about flu symptoms and personal belief of previous COVID-19 infections. The period in which contact to SARS-CoV-2 positive patients has been possible was 10 months (March to December 2020)-with 54,681 patient contacts documented for EMS-either emergencies (n = 33,241) or transportation services (n = 21,440). Seven hundred-thirty (n = 730) participants were included into the study (n = EMS: 325, HS: 322 and NPC: 83). The analysis of the survey showed that the exposure to patients with an unknown and consecutive positive SARS-CoV-2 result was significantly higher for EMS when compared to HS (EMS 55% vs. HS 30%, p = 0.01). The incidence of a SARS-CoV-2 infection in our cohort was 1.2% (EMS), 2.2% (HS) and 2.4% (NPC) within the three groups (ns) and lowest in EMS. Furthermore, the belief of previous COVID-19 was significant higher in EMS (19% vs. 10%), CONCLUSION: The consistent use of FFP2/N95 in EMS is able to prevent work-related SARS-CoV-2 infections in emergency situations. The significance of physical airway protection in exposed medical staff is still relevant especially under the aspect of new viral variants and unclear effectiveness of new vaccines.


Capsule types of Klebsiella pneumoniae isolated from the genital tract of mares with metritis, extra-genital sites of healthy mares and the genital tract of stallions.
A survey of K. pneumoniae was performed on cervical swabs, feces and nasal swabs of mares and on samples from the genital tract of stallions from 1980 to 1986 in south-western Hokkaido, Japan. K1 was the predominant type (79 of 88, 89.8%) in the metritis cases due to K. pneumoniae in mares of racing breeds. The same type was isolated from semen and swabs of the fossa glandis of 6 of 20 (30.0%) of the stallions of racing breeds. Heavily encapsulated and less heavily encapsulated K1 strains were isolated from the stallions. Mares bred to stallions carrying heavily encapsulated strains developed metritis, while those bred to stallions carrying less heavily encapsulated strains did not. K39 was isolated from cervical swabs solely from metritis-infected mares of draft breeds and not from any mares of the racing breeds examined. Untypable strains were isolated from cervical swabs in 7 of 88 (8.0%) metritis cases of mares of racing breeds and from semen in 7 of 19 (36.8%) stallions of racing breeds and they were predominant in feces (19 of 21, 90.5%) and nasal swabs (3 of 4, 75.0%) of healthy mares of racing breeds.


Epidemiology of inflammatory bowel disease in the Republic of San Marino: The "EPIMICI - San Marino" study.
The burden of Crohn's disease (CD) and ulcerative colitis (UC) has never been estimated in the Republic of San Marino, the third smallest nation of the world. To assess the occurrence and clinical features of CD and UC in San Marino during the last 35 years. We retrospectively evaluated the prevalence, incidence, and main clinical aspects of CD and UC from 1980 to 2014, crossing data from various sources. Prevalence rates (per 100,000) on December 31, were 241 for CD (263 in males and 220 in females) and 311 for UC (370 in males and 255 in females). The specific incidence of UC steadily increased from 4.6 (95% CI: 1.5-10.6) in 1980-1984 to 12.4 (95% CI: 7.6-19.1) in 2010-2014; CD incidence showed a higher proportional increase, from 1.8 (95% CI: 0.2-6.6) in 1980-1984 to 17.9 (95% CI: 12.0-25.7) in 2010-2014. The main clinical features of CD and UC (activity and location at diagnosis, extra-intestinal manifestations, disease progression overtime, therapies, and hospitalizations) were analyzed. This study provides the first epidemiological report on CD and UC in San Marino, showing specific traits and overall higher prevalence and incidence rates than previously reported in neighbor Areas.


Single-cell analysis reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of ovarian cancer.
High-grade serous ovarian carcinoma (HGSOC) is a heterogeneous disease, and a high stromal/desmoplastic tumor microenvironment (TME) is associated with a poor outcome. Stromal cell subtypes, including fibroblasts, myofibroblasts, and cancer-associated mesenchymal stem cells, establish a complex network of paracrine signaling pathways with tumor-infiltrating immune cells that drive effector cell tumor immune exclusion and inhibit the antitumor immune response. Single-cell transcriptomics of the HGSOC TME from public and in-house datasets revealed a distinct transcriptomic landscape for immune and non-immune cells in high-stromal vs. low-stromal tumors. High-stromal tumors had a lower fraction of certain T cells, natural killer (NK) cells, and macrophages and increased expression of CXCL12 in epithelial cancer cells and cancer-associated mesenchymal stem cells (CA-MSCs). Analysis of cell-cell communication indicated that epithelial cancer cells and CA-MSCs secreted CXCL12 that interacted with the CXCR4 receptor, which was overexpressed on NK and CD8 + T cells. CXCL12 and/or CXCR4 antibodies confirmed the immunosuppressive role of CXCL12-CXCR4 in high-stromal tumors.


Ibotenic acid and thioibotenic acid: a remarkable difference in activity at group III metabotropic glutamate receptors.
In this study, we have determined and compared the pharmacological profiles of ibotenic acid and its isothiazole analogue thioibotenic acid at native rat ionotropic glutamate (iGlu) receptors and at recombinant rat metabotropic glutamate (mGlu) receptors expressed in mammalian cell lines. Thioibotenic acid has a distinct pharmacological profile at group III mGlu receptors compared with the closely structurally related ibotenic acid; the former is a potent (low microm) agonist, whereas the latter is inactive. By comparing the conformational energy profiles of ibotenic and thioibotenic acid with the conformations preferred by the ligands upon docking to mGlu1 and models of the other mGlu subtypes, we propose that unlike other subtypes, group III mGlu receptor binding sites require a ligand conformation at an energy level which is prohibitively expensive for ibotenic acid, but not for thioibotenic acid. These studies demonstrate how subtle differences in chemical structures can result in profound differences in pharmacological activity.


Reliability and Validity of the Composite Activity-Related Fall Risk Scale.
The newly developed Composite Activity-related Risk of Falls Scale (CARFS) is designed to measure composite activity-related risk of falls (CARF) in relation to the activity-specific fear of falling and physical behavior. This study tested the reliability and validity of the CARFS in older people with various health statuses and persons with stroke or spinal cord injury. Participants included 70 older adults, 38 persons with stroke, and 18 with spinal cord injury. They were first surveyed using a combined questionnaire including the CARFS and activity-specific balance confidence (ABC) scale in addition to items asking for personal and disease-related information, fall history, walking independence levels for examining internal consistency, ceiling and floor effects, and convergent validity in each participant group. One week after the initial survey, 33 older participants were reexamined using the CARFS to analyze test-retest reliability, where a minimal detectable change was found. Significance was set at α = 0.05 for all analyses. The CARFS showed excellent test-retest reliability in the dimensions of fear of falling, physical behavior, and CARF [ICC (3,1) = 0.972, 0.994, and 0.994, respectively for their overall score], with a minimal detectable change of 3.944 in the older population. The internal consistency of CARFS items was excellent in the older participants, good in participants with stroke or spinal cord injury (Cronbach's alpha = 0.945, 0.843, 0.831 in each participant group, respectively). No ceiling and floor effects were demonstrated in the wide range of people. For the convergent validity, overall CARF score was significantly correlated with the average ABC score in each participant group (rho = -0.824, -0.761, and -0.601, respectively; p < 0.01), and was significantly correlated with walking independence levels in each participant group (rho = -0.636, -0.423, and -0.522, respectively; p < 0.01). It showed weak correlation with the number of previous falls only in participants with stroke (rho = 0.291, p = 0.076). The CARFS is a reliable and valid tool for measuring fall risk in older people and persons with stroke or spinal cord injury.


DNA methylome in pancreatic cancer identified novel promoter hyper-methylation in NPY and FAIM2 genes associated with poor prognosis in Indian patient cohort.
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading cancers worldwide and has a poor survival, with a 5-year survival rate of only 8.5%. In this study we investigated altered DNA methylation associated with PDAC severity and prognosis. Methylome data, generated using 450 K bead array, was compared between paired PDAC and normal samples in the TCGA cohort (n = 9) and our Indian cohort (n = 7). The total Indian Cohort (n = 75) was split into cohort 1 (n = 7), cohort 2 (n = 22), cohort 3 (n = 26) and cohort 4 (n = 20).Validation of differential methylation (6 selected CpG loci) and associated gene expression for differentially methylated genes (10 selected gDMs) were carried out in separate validation cohorts, using MSP, RT-PCR and IHC correlations between methylation and gene expression were observed in TCGA, GTEx cohorts and in validation cohorts. Kaplan-Meier survival analysis was done to study differential prognosis, during 2-5 years of follow-up. We identified 156 DMPs, mapped to 91 genes (gDMs), in PDAC; 68 (43.5%) DMPs were found to be differentially methylated both in TCGA cohort and our cohort, with significant concordance at hypo- and hyper-methylated loci. Enrichments of "regulation of ion transport", "Interferon alpha/beta signalling", "morphogenesis and development" and "transcriptional dysregulation" pathways were observed among 91 gDMs. Hyper-methylation of NPY and FAIM2 genes with down-regulated expression in PDAC, were significantly associated with poor prognosis in the Indian patient cohort. Ethnic variations among populations may determine the altered epigenetic landscape in the PDAC patients of the Indian cohort. Our study identified novel differentially methylated genes (mainly NPY and FAIM2) and also validated the previously identified differentially methylated CpG sites associated with PDAC cancer patient's survival. Comparative analysis of our data with TCGA and CPTAC cohorts showed that both NPY and FAIM2 hyper-methylation and down-regulations can be novel epigenetically regulated genes in the Indian patient population, statistically significantly associated with poor survival and advanced tumour stages.


Comparison of five commonly used automated susceptibility testing methods for accuracy in the China Antimicrobial Resistance Surveillance System (CARSS) hospitals.
The objective of this study was to evaluate the performance of five commonly used automated antimicrobial susceptibility testing (AST) systems in China (Vitek 2, Phoenix, Microscan, TDR, and DL). Two "unknown" isolates, S1 (ESBL-producing Escherichia coli) and S2 (KPC-producing Klebsiella pneumoniae), were sent to 886 hospitals in China for identification and AST. Using broth microdilution method (BMD) as gold standard, minimum inhibitory concentrations (MICs) were determined. Most hospitals (392, 46.1%) used Vitek 2, followed by 16% each for Phoenix, Microscan, and DL systems, and 5.9% (50) used TDR system. MICs of 22 antimicrobials were evaluated for two study isolates plus three ATCC strains. Individual susceptibility results for three ATCC strains (n=1581) were submitted by 780 (91.2%) hospitals. For each AST system, 8.7% (6/69) to 13.0% (33/253) reported MICs outside the expected range for several drugs. For the two study isolates, TDR and DL systems performed the worst in MIC determination and susceptibility categorization of cefazolin and cefepime, while the Microscan system had difficulties in susceptibility categorization for aztreonam and ertapenem. Categorical agreements were >90% for most antimicrobials tested for both the isolates, among which, using BMD, no essential agreements were noted for ampicillin, piperacillin, cefazolin, cefuroxime, ceftriaxone, and trimethoprim/sulfamethoxazole. All AST systems except Vitek 2 showed unacceptable VMEs for cefazolin (S1 and S2) and major errors for ceftazidime, cefepime, and aztreonam (isolate S1), while Vitek 2 showed a high VME rate for cefepime (10.0%) and meropenem (6.2%) for S2. None of the five automated systems met the criteria for acceptable AST performance, but Vitek 2 provided a relatively accurate and conservative performance for most of the antimicrobials.


Essential oil of Bassia muricata: Chemical characterization, antioxidant activity, and allelopathic effect on the weed Chenopodium murale.
The essential oil (EO) of Bassia muricata shoots was extracted via hydro-distillation and then investigated by gas chromatography-mass spectrometry. Thirty-four compounds were recognized for the first time from this plant, representing 100% of the total mass. Terpenoids represented the major components with 69.17% of the total mass, containing oxygenated sesquiterpenes (53.18%), oxygenated monoterpenes (9.77%), sesquiterpene hydrocarbons (5.03%), and diterpenes (1.19%). Additionaly, 6-methoxy-1-acetonaphthone was the only aromatic compound represented in a high percentage of the total identified compounds with 22.35%. Additionally, a percent of 8.48% of the total mass was hydrocarbons. Only one oxygenated sesquiterpene namely hexahydrofarnesyl acetone representing 47.35% of the total mass was identified. It was followed by methoxy-1-acetonaphthone (19.92%), n-dotriacontane (3.58%), endo-borneol (3.24%), 6-methy-α-ionone (3.04%), and α-gurjunene (2.65%). The EO exhibited moderate antioxidant activity comparable with ascorbic acid as a standard, where it attained IC50 value of 20.70 µL L-1 and 16.32 µL L-1, for DPPH and ABTS. The EO of B. muricata significantly reduces the germination and seedling development of the weed Chenopodium murale. The EO showed an IC50 value of 175.60 µL L-1, 246.65 µL L-1, and 308.33 µL L-1 for root growth, shoot growth, and germination, respectively. Therefore, this EO could be a good green resource for the control of weeds.


Kagami-Ogata syndrome: a clinically recognizable upd(14)pat and related disorder affecting the chromosome 14q32.2 imprinted region.
Human chromosome 14q32.2 carries paternally expressed genes including DLK1 and RTL1, and maternally expressed genes including MEG3 and RTL1as, along with the germline-derived DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and the postfertilization-derived MEG3-DMR. Consistent with this, paternal uniparental disomy 14 (upd(14)pat), and epimutations (hypermethylations) and microdeletions affecting the IG-DMR and/or the MEG3-DMR of maternal origin, result in a unique phenotype associated with characteristic face, a small bell-shaped thorax with coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly and polyhydramnios. Recently, the name 'Kagami-Ogata syndrome' (KOS) has been approved for this clinically recognizable disorder. Here, we review the current knowledge about KOS. Important findings include the following: (1) the facial 'gestalt' and the increased coat-hanger angle constitute pathognomonic features from infancy through childhood/puberty; (2) the unmethylated IG-DMR and MEG3-DMR of maternal origin function as the imprinting control centers in the placenta and body respectively, with a hierarchical interaction regulated by the IG-DMR for the methylation pattern of the MEG3-DMR in the body; (3) RTL1 expression level becomes ~2.5 times increased in the absence of functional RTL1as-encoded microRNAs that act as a trans-acting repressor for RTL1; (4) excessive RTL1 expression and absent MEG expression constitute the primary underlying factor for the phenotypic development; and (5) upd(14)pat accounts for approximately two-thirds of KOS patients, and epimutations and microdeletions are identified with a similar frequency. Furthermore, we refer to diagnostic and therapeutic implications.


Rapastinel, a novel glutamatergic agent with ketamine-like antidepressant actions: Convergent mechanisms.
Conventional antidepressant medications, which act on monoaminergic systems, have significant limitations, including a time lag of weeks to months and low rates of therapeutic efficacy. Recently, clinical findings demonstrate that ketamine, a dissociative anesthetic that blocks N-methyl-d-aspartate (NMDA) receptor channel activity, causes rapid (within hours) and long-lasting (7 to 10 days) antidepressant effects. Rapastinel is a novel glutamatergic compound that acts as an NMDAR postive allosteric modulator and produces rapid antidepressant actions in depressed patients and in preclinical rodent models. In addition, rapastinel has no ketamine-like side effect such as cognitive impairment and psychotomimetic symptoms. Despite recent negative clinical trials, it remains possible that rapastinel could prove effective as an alternative rapid agent with reduced side effects. In this review, we discuss the pharmacological profile of rapastinel and the molecular and cellular mechanisms underlying the rapid and sustained antidepressant actions of this novel agent.


Induction and quantitative proteomic analysis of cell dedifferentiation during callus formation of lotus (Nelumbo nucifera Gaertn.spp. baijianlian).
Lotus is an aquatic plant with high nutritional, ornamental and medical values. Its callus formation is crucial for germplasm innovation by genetic transformation. In this study, embryogenic callus was successfully induced on appropriate medium using cotyledons at 12days after pollination as explants. To dissect cellular dedifferentiation and callus formation processes at the proteome level, cotyledons before and tissues from 10 to 20days after induction were sampled for shotgun proteomic analysis. By applying multivariate statistics 91 proteins were detected as differentially regulated, and sorted into 6 functional groups according to MapMan ontology analysis. Most of these proteins were implicated in various metabolisms, demonstrating that plant cells underwent metabolism reprogramming during callus induction. 14.3% proteins were associated with stress and redox, indicating that the detached explants were subjected to a variety of stresses; 13.2% were cell and cell wall-related proteins, suggesting that these proteins played important roles in rapid cell division and proliferation. Some proteins were further evaluated at the mRNA levels by quantitative reverse transcription PCR analysis. In conclusion, the results contributed to further deciphering of molecular processes of cellular dedifferentiation and callus formation, and provided a reference data set for the establishment of transgenic transformation in lotus.


Isoflavones and hypercholesterolemia in rats.
Isoflavones isolated from three commonly used pulses such as Bengalgram (Cicer arietinum), greengram (Phaseolus aureus) and blackgram (Phaseolus mungo) and p-coumaric acid were supplemented to hypercholesterolemia-inducing diet of rats. Among isoflavones, Biochanin A and Formononetin showed hypolipidemic activity but diadzein did not; p-coumaric acid also produced a significant reduction in serum cholesterol levels.


NOx emission deterioration in modern heavy-duty diesel vehicles based on long-term real driving measurements.
NOx emissions from diesel vehicles generally deteriorate with increased durability mileage owing to the wear and deterioration of engines and after-treatment systems. Three China-VI heavy-duty diesel vehicles (HDDVs) were selected for four-phase long-term real driving emission (RDE) tests using the portable emission measurement system (PEMS). After 200,000 km of on-road driving, the maximum NOx emission factor of the test vehicles (387.06 mg/kWh) was found to be significantly lower than the NOx limit of 690 mg/kWh. Under all driving conditions, the NOx conversion efficiency of selected catalytic reduction (SCR) decreased almost linearly as the durability mileage increased. Importantly, the deterioration rate of the NOx conversion efficiency in low-temperature intervals was discernibly higher than that in high-temperature intervals. The NOx conversion efficiency at 200 °C dropped by 16.67-19.82% with higher durability mileage; however, the highest values at 275-400 °C only decreased by 4.11%. Interestingly, the SCR catalyst at 250 °C showed strong NOx conversion efficiency and durability (maximum decline of 2.11%). Overall, the poor de-NOx performance of SCR catalysts at low temperatures significantly challenges the long-term effective control of NOx emissions from HDDVs. Thus, improving the NOx conversion efficiency and durability at low-temperature intervals is the top priority for SCR catalyst optimization; NOx emissions from HDDVs at low velocities and loads should also be monitored by environmental authorities. The linear fitting coefficient for the NOx emission factors of the four-phase RDE tests was 0.90-0.92, indicating that NOx emissions deteriorated linearly with an increase in mileage. Based on the linear fitting results, the NOx emission control of the test vehicles during 700,000 km of on-road driving was highly likely to be qualified. These results can be used by environmental authorities to supervise the NOx emission conformity of in-use HDDVs after validation using other types of vehicles.


Traumatic lung laceration secondary to avulsed lung adhesion - A case report.
Pulmonary lacerations caused by an avulsion force on an adhesion between the lung and chest wall following blunt thoracic injury are very rare. They may result in pneumothorax and/or hemothorax and may not be immediately apparent clinically or radiologically. We present the case of a healthy 34-year-old male who sustained blunt thoracic injury. He was clinically stable, and his initial routine images were unremarkable. The patient was discharged home on the same day. He presented a week later with a massive hemothorax requiring surgical intervention which revealed bleeding from an avulsed adhesion between the lung and chest wall. Bleeding was successfully controlled by hemostatic agent, and the patient had an uneventful recovery. Hemothorax requiring intervention from an avulsed adhesion may occur following blunt thoracic trauma. Initial imaging and clinical finding may be misleading. Close follow up and adequate patient education should be ensured prior to discharge following seemingly trivial trauma.


Local protein-DNA interactions may determine nucleosome positions on yeast plasmids.
The structure of the nucleosome core particle, the basic structural subunit of chromatin, is well known. Although nucleosomes often appear to be positioned randomly with respect to DNA sequences, in some cases they seem to occupy precisely defined positions on the DNA. The yeast plasmid TRP1ARS1 contains three precisely positioned, stable nucleosomes, I, II and III, which are flanked by nuclease-sensitive regions. Our aim in the present study was to determine whether the positions of these three nucleosomes relate to (1) protein-DNA interactions; (2) the limited space between nuclease-sensitive regions, which is just long enough to accommodate three yeast nucleosomes (that is, boundary conditions); or (3) proximity to the putative origin of replication in one of the nuclease-sensitive regions. We have tested these alternatives by analysing the positions of nucleosomes after insertion of various lengths of DNA into this region and assembly of chromatin in vivo. Our results suggest that specific protein-DNA interactions are the most likely determinants of these nucleosome positions.


Isolation and identification of chitin in the black coral Parantipathes larix (Anthozoa: Cnidaria).
Until now, there is a lack of knowledge about the presence of chitin in numerous representatives of corals (Cnidaria). However, investigations concerning the chitin-based skeletal organization in different coral taxa are significant from biochemical, structural, developmental, ecological and evolutionary points of view. In this paper, we present a thorough screening for the presence of chitin within the skeletal formations of a poorly investigated Mediterranean black coral, Parantipathes larix (Esper, 1792), as a typical representative of the Schizopathidae family. Using a wide array variety of techniques ((13)C solid state NMR, Fourier transform infrared (FTIR), Raman, NEXAFS, Morgan-Elson assay and Calcofluor White Staining), we unambiguously show for the first time that chitin is an important component within the skeletal stalks as well as pinnules of this coral.


Metabolic-associated fatty liver disease increases the risk of end-stage renal disease in patients with biopsy-confirmed diabetic nephropathy: a propensity-matched cohort study.
To investigate the relationship between metabolic-associated fatty liver disease (MAFLD) and end-stage renal disease (ESRD) in patients with biopsy-confirmed diabetic nephropathy (DN). A total of 316 participants with biopsy-confirmed DN between January 2008 and December 2019 were retrospectively assessed. Kaplan-Meier curve and Cox proportional hazard models were used to compare the risk of incident ESRD in 50 patients with MAFLD and 50 patients without MAFLD, after using propensity score matching (PSM) to address the imbalances of sex, age, baseline-estimated glomerular filtration rate, serum albumin, 24-h urine protein, hemoglobin and systolic blood pressure. During the median follow-up period of 3 years, there were 19 ESRD outcome events (19%) in PSM cohort. Kaplan-Meier curve analysis suggested that renal survival significantly deteriorated in patients with MAFLD versus those without MAFLD (p = 0.021). Additionally, the hazard ratios (95% confidence interval) of MAFLD were 3.12 (1.09-8.95, p = 0.035), 3.36 (1.09-10.43, p = 0.036), 3.66 (1.22-10.98, p = 0.021), 4.25 (1.34-13.45, p = 0.014), 3.11 (1.08-8.96, p = 0.035) and 5.84 (1.94-18.5, p = 0.003) after adjustment for six models, including demographic, clinical and pathological characteristics as well as medication use at the time of renal biopsy, respectively. Besides, patients with higher liver fibrosis score had a greater possibility of ESRD, comparing to those with lower liver fibrosis score (p = 0.002). MAFLD increases the risk of incident ESRD in patients with biopsy-proven DN. Further research is needed to determine whether treatment targeting MAFLD improves the prognosis of DN.


Crystal structure of 9,20-dimethyl-1,8,12,19-tetra-aza-tetra-cyclo-[17.3.1.02,7.013,18]tricosane dihydrate from synchrotron X-ray data.
The structure of the title compound, C21H40N4·2H2O, has been determined from synchrotron X-ray radiation data. The asymmetric unit comprises one 12-membered macropolycycle and two lattice water mol-ecules. The macropolycycle contains two cyclo-hexane rings and one 1,3-di-aza-cyclo-hexane ring, all in chair conformations. The C-N and C-C bond lengths are in the ranges 1.4526 (16)-1.4786 (17) and 1.517 (2)-1.5414 (17) Å, respectively. One intra-molecular N-H⋯N hydrogen bond helps to stabilize the mol-ecular conformation while medium-strength inter-molecular N-H⋯O, O-H⋯N and O-H⋯O hydrogen bonds involving the lattice water mol-ecules connect the components into a three-dimensional network.


Intrathecal serotonin in mice: analgesia and inhibition of a spinal action of substance P.
Serotonin, administered intrathecally in mice, produced dose-related analgesia in the tail flick test and the subcutaneous hypertonic saline assay. Low doses (2.5-5 ng) of serotonin blocked the biting and scratching response elicited by intrathecal substance P. However, higher doses of serotonin itself elicited a behavioral syndrome characterized by scratching of the torso with the hindlimbs. Both the analgesic response and the scratching response due to serotonin were blocked by specific serotonin antagonists and the analgesia is likely mediated by a postsynaptic action on dorsal horn nociceptive neurons.


Protocol for electrotaxis of large epithelial cell sheets.
Here, we present a protocol for electrotaxis of large epithelial cell sheets without compromising the integrity of cell epithelia in a high-throughput customized directed current electrotaxis chamber. We describe the fabrication and use of polydimethylsiloxane stencils to control the size and shape of human keratinocyte cell sheets. We detail cell tracking, cell sheet contour assay, and particle image velocimetry to reveal the spatial and temporal motility dynamics of cell sheets. This approach is applicable to other collective cell migration studies. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2022).1.


Harnessing cellular-derived forces in self-assembled microtissues to control the synthesis and alignment of ECM.
The alignment and blend of extracellular matrix (ECM) proteins give a tissue its specific mechanical properties as well as its physiological function. Various tissue engineering methods have taken purified ECM proteins and aligned them into gels, sponges and threads. Although, each of these methods has created aligned ECM, they have had many limitations including loss of hierarchal collagen structure and poor mechanical performance. Here, we have developed a new method to control ECM synthesis using self-assembled cells. Cells were seeded into custom designed, scaffold-free, micro-molds with fixed obstacles that harnessed and directed cell-mediated stresses. Cells within the microtissue reacted to self-generated tension by aligning, elongating, and synthesizing an ECM whose organization was dictated by the strain field that was set by our micro-mold design. We have shown that through cell selection, we can create tissues with aligned collagen II or aligned elastin. We have also demonstrated that these self-assembled microtissues have mechanical properties in the range of natural tissues and that mold design can be used to further tailor these mechanical properties.


Relationship between manometric and videofluoroscopic measures of swallow function in healthy adults and patients treated for head and neck cancer with various modalities.
Pharyngeal manometry complements the modified barium swallow with videofluoroscopy (VFS) in diagnosing pressure-related causes of dysphagia. When manometric analysis is not feasible, it would be ideal if pressure information about the swallow could be inferred accurately from the VFS evaluation. Swallowing function was examined using VFS and concurrent manometry in 18 subjects (11 head and neck patients treated with various modalities and 7 healthy adults). Nonparametric univariate and multivariate analyses revealed significant relationships between manometric and fluoroscopic variables. Increases in pressure wave amplitude were significantly correlated with increased duration of tongue base to pharyngeal wall contact, reduced bolus transit times, and oropharyngeal residue. Pharyngeal residue was the most important VFS variable in reflecting pharyngeal pressure measurements. Certain VFS measures were significantly correlated with measures of pressure assessed with manometry. Further research is needed before observations and measures from VFS alone may be deemed sufficient for determining pressure-generation difficulties during the swallow in patients who are unable or unwilling to submit to manometric testing.


Schizophreniform disorder, delusional disorder and psychotic disorder not otherwise specified: clinical features, outcome and familial psychopathology.
The relationship between DSM-III-R schizophreniform disorder, delusional disorder (DD) and psychotic disorder not otherwise specified (PD-NOS) and schizophrenia and affective illness (AI) remains uncertain. We explore this question in the Roscommon Family Study by examining symptoms, outcome and patterns of psychopathology in relatives. Probands were selected from a population-based case registry in the west of Ireland with an ICD-9 diagnosis of schizophrenia or AI. Personal interviews were conducted with 88% of traceable, living probands, a mean of 16 years after onset, and 86% of traceable, living first-degree relatives. Best-estimate diagnoses were made at follow-up. Schizophreniform disorder, DD and PD-NOS constituted 6.4%, 2.8% and 7.5%, respectively, of all probands with a registry diagnosis of schizophrenia. Probands with schizophreniform disorder had prominent positive psychotic symptoms, negligible negative symptoms and a good outcome, comparable to that seen in AI probands. Their relatives had an excess risk of schizophrenia spectrum illness but not AI. Probands with DD had prominent delusions but no other psychotic symptoms, few negative symptoms, fair to good outcome and an increased risk in relatives for alcoholism. Probands with PD-NOS had both moderate positive and negative psychotic symptoms, a poor to fair outcome and a substantially elevated risk in relatives of schizophrenia and schizophrenia spectrum disorders but not AI.(ABSTRACT TRUNCATED AT 250 WORDS)


Short-term folic acid supplementation induces variable and paradoxical changes in plasma homocyst(e)ine concentrations.
Folic acid is presently the mainstay of treatment for most subjects with elevated plasma homocyst(e)ine concentrations [Plasma or serum homocyst(e)ine, or total homocysteine, refers to the sum of the sulfhydryl amino acid homocysteine and the homocysteinyl moieties of the disulfides homocystine and homocystein-cysteine, whether free or bound to plasma proteins.] Changes in homocyst(e)ine in response to folic acid supplementation are characterized by considerable interindividual variation. The purpose of this study was to identify factors that contribute to heterogeneity in short-term responses to folic acid supplementation. The effects of folic acid supplementation (1 or 2 mg per day) for 3 wk on plasma homocyst(e)ine concentrations were assessed in 304 men and women. Overall, folic acid supplementation increased mean plasma folate 31.5 +/- 98.0 nmol/L and decreased mean plasma homocyst(e)ine concentrations 1.2 +/- 2.4 micromol/L. There was evidence of substantial interindividual variation in the homocyst(e)ine response from -18.5 to +7.1 micromol/L, including an increase in homocyst(e)ine in 20% of subjects (mean increase 1.5 +/- 1.4 micromol/L). Basal homocyst(e)ine, age, male gender, cigarette smoking, use of multivitamins, methylene tetrahydrofolate reductase, and cystathionine beta-synthase polymorphisms accounted for 47.6% of the interindividual variability in the change in homocyst(e)ine after folic acid supplementation, but about 50% of variability in response to folic acid was not explained by the variables we studied.


Dendritic cell-based cancer immunotherapy: potential for treatment of colorectal cancer?
Human tumours including those of the gastrointestinal tract express a number of specific antigens that can be recognized by T cells, thus providing potential targets for cancer immunotherapy. Dendritic cells (DC) are rare leucocytes that are uniquely potent in their ability to capture, process and present antigens to T cells, and so selectively migrate through tissues to reach lymph nodes and spleen where initiation of immune responses takes place. Studies in murine tumour models have shown clearly that DC are capable of presenting tumour antigens to initiate tumour-specific cytotoxic T cell responses, and DC vaccination can induce anti-tumour activity against both primary tumours and pre-established tumour metastases. These findings together with the ability to culture sufficient numbers of DC from human bone marrow or blood progenitors have prompted the current major interest in their potential use in human tumour vaccination. Vaccine production involves harvesting autologous DC from cultured peripheral blood mononuclear cells in the presence of a cocktail of cytokines, ex vivo exposure of the DC to tumour antigens and return of pulsed DC to the patient to induce tumour immunity. Reports from Phase I/II clinical trials indicate that DC vaccines are safe with little or no side effect, and are capable of initiating antigen-specific T cell responses. Furthermore, defined tumour antigens are not necessarily required, which may make the process more applicable to human cancers, including many gastrointestinal cancers that lack well-characterized tumour-specific antigens. Additional trials of DC vaccination for a variety of human cancers including colorectal cancers are under way, and refinement of vaccine protocols and methods for targeting tumour antigens to DC in vivo are also being explored. There is reason to believe that DC-based vaccination could become an adjunct to current treatments for human cancers including colorectal cancer in the foreseeable future.


Factors influencing contraceptive behavior of single college students.
This study investigated the premarital contraceptive behavior of 222 male and female college students. Contraceptive practice was examined in relation to dating patterns, level of emotional involvement with the sex partner was heightened, the intercourse was planned, and the individual and prior sexual experience.


Stakeholder Perspectives on the Social Determinants of Mental Health in Community Coalitions.
Although evidence supports the potential for community coalitions to positively address social determinants of mental health, little is known about the views of stakeholders involved in such efforts. This study sought to understand county leaders' perspectives about social determinants related to the Health Neighborhood Initiative (HNI), a new county effort to support community coalitions. Descriptive, qualitative study, 2014. Community coalitions, located in a large urban city, across eight service planning areas, that serve under-resourced, ethnic minority populations. We conducted key informant interviews with 49 health care and community leaders to understand their perspectives about the HNI. As part of a larger project, this study focused on leaders' views about social determinants of health related to the HNI. All interviews were audio-recorded and transcribed. An inductive approach to coding was used, with text segments grouped by social determinant categories. County leaders described multiple social determinants of mental health that were relevant to the HNI community coalitions: housing and safety, community violence, and employment and education. Leaders discussed how social determinants were interconnected with each other and the need for efforts to address multiple social determinants simultaneously to effectively improve mental health. Community coalitions have an opportunity to address multiple social determinants of health to meet social and mental health needs of low-resourced communities. Future research should examine how community coalitions, like those in the HNI, can actively engage with community members to identify needs and then deliver evidence-based care.


SHEF: a vHTS geometrical filter using coefficients of spherical harmonic molecular surfaces.
SHEF (spherical harmonic coefficient filter), a geometrical matching procedure constituting a preliminary step in the virtual high throughput screening of large databases of small drug-like molecules, is demonstrated. This filter uses a description of both the binding site of the target and the ligand surfaces using spherical harmonic polynomial expansions. Using this representation, which is based on limited sets of spherical harmonic coefficients, considerably reduces the complexity of surface complementarity calculation. As a first test, 188 known protein-ligand complexes were used, and the results of docking the abstracted ligands into the bare proteins using SHEF were compared to the original X-ray structures. The ability of SHEF to retrieve known ligands "hidden" in a virtual library of 1,000 randomly selected drug-like compounds is also demonstrated.


Impact of the FTO gene variation on fat oxidation and its potential influence on body weight in women with polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder where insulin resistance might be involved in the development of endocrine and metabolic abnormalities. It has recently been shown that the FTO gene modifies weight, fat mass and insulin sensitivity in women with PCOS, where its role might be larger than in other phenotypes. The aim of this study was to estimate the effect of a variation of the FTO gene on carbohydrate and lipid oxidation in PCOS women. The study group consisted of 65 women with PCOS and 28 healthy, normally menstruating women. Clinical examination, anthropometric measurements, euglycaemic hyperinsulinaemic clamp and measurements of serum sex hormones were performed. Carbohydrate and lipid oxidation were evaluated with indirect calorimetry in the baseline state and during last 30 min of the clamp. The FTO rs9939609 polymorphism was genotyped using the restriction fragment length polymorphism method. There were no differences in carbohydrate and lipid oxidation between PCOS and control women. In the PCOS group, TT homozygotes had higher baseline fat oxidation in comparison with carriers of the A allele (P = 0·018), which was not found in the control group. We did not observe the effect of the FTO gene variation on insulin-stimulated lipid oxidation and neither on the baseline nor on the insulin-stimulated carbohydrate oxidation. Our data show that this FTO gene variation might influence the baseline lipid oxidation in PCOS patients. This might potentially be one of the mechanisms explaining the impact of the FTO gene on body weight in PCOS.


Preparative isolation and purification of salvianolic acid B from the Chinese medicinal plant Salvia miltiorrhiza by high-speed counter-current chromatography.
High-speed counter-current chromatography was applied to the isolation and purification of salvianolic acid B from the Chinese medicinal plant Salvia miltiorrhiza Bunge. The crude salvianolic acid B was obtained by extraction with ethanol-water from S. miltiorrhiza Bunge. Preparative high-speed counter-current chromatography with a two-phase solvent system composed of n-hexane-ethyl acetate-ethanol-water (3:7:1:9, v/v) was successfully performed yielding 342 mg salvianolic acid B at 98% purity from 500 mg of the crude extract in a one-step separation.


Concatenating Suzuki Arylation and Buchwald-Hartwig Amination by A Sequentially Pd-Catalyzed One-Pot Process-Consecutive Three-Component Synthesis of C,N-Diarylated Heterocycles.
The concatenation of Suzuki coupling and Buchwald-Hartwig amination in a consecutive multicomponent reaction opens a concise, modular and efficient one-pot approach to diversely functionalized heterocycles, as exemplified for 3,10-diaryl 10H-phenothiazines, 3,9-diaryl 9H-carbazoles, and 1,5-diaryl 1H-indoles, in high yields starting from simple staring materials. Moreover, this one-pot reaction is a sequentially palladium-catalyzed process that does not require additional catalyst loading after the first coupling step.


A case-report of idiopathic juvenile osteoporosis with particular reference to 47-calcium absorption.
Calcium metabolism was studied in a 12-year-old girl preseting with idiopathic juvenile osteoporosis. Absorption of orally administered 47-Ca was high. Serum calcium and phosphorus, serum immunoreactive PTH and CT and tubular phosphate reabsorption were found to be within normal limits. The data suggest that calcium malabsorption, nutritional calcium deficiency, hyperparathyroidism, a dysfunction related to sex hormones, and Cushing's syndrome cannot be implicated in the aetiology of the osteoporosis in this case who recovered spontaneously with sexual maturation.


Fetal brain tumors.
Fetal intracranial tumors are rare and their evolution is usually poor. With routine use of antenatal ultrasound imaging, a larger number of such tumors have been diagnosed. During the period from January 1992 to January 2002, 18 cases diagnosed as intracranial tumors in the fetal stage were treated in the Neurosurgery and Obstetrics Departments of the Federal University of São Paulo and in the Fetal Medicine Service of the Maternity Hospital Santa Joana. The tumors most frequently found were those of the choroid plexus and teratomas. Out of those 18 cases, 11 patients presented with fetal hydrocephalus, and 5 of them, who were less than 34 weeks old (gestational age), underwent repeated cephalocenteses while awaiting better conditions for delivery. Two fetuses died while in utero before any intervention had taken place and 16 underwent craniotomy after birth. Twelve of those patients are still alive, 9 of whom are considered normal. The 3 others are slightly or moderately retarded.


Prevalence of hepatitis B and C viruses infection among military personnel at Bahir Dar Armed Forces General Hospital, Ethiopia.
Military personnel are high-risk people for parenteral and sexually transmitted diseases such as hepatitis B virus (HBV) and hepatitis C virus (HCV). Data regarding HBV and HCV prevalence among military personnel in Ethiopia is limited. Hence, the study aimed to determine sero-prevalence and associated risk factors of HBV and HCV among military personnel at Bahir Dar Armed Forces General Hospital, Ethiopia. A cross-sectional study was conducted in a total of 403 military personnel from February to May 2015. Socio-demographic characteristics and risk factors were collected through face to face interview using structured questionnaire. HBV and HCV infection was determined using HBsAg and anti-HCV antibody rapid tests. Logistic regression analysis was employed to assess possible risk factors for HBV and HCV infections. The sero-prevalence of HBV and HCV infection were 4.2 and 0.2%, respectively. None of the study subjects were co-infected with HBV and HCV. Higher prevalence of HBV infection (11.3%) was observed in the age group of 40 and above. Being at the age of 40 years and above (COR 7.6; 95% CI 2.0-29.0, p = 0.003), history of nose piercing (COA 5.9; 95% CI 1.2-29.9, p = 0.033) and sexually transmitted infection (COR 4.3; 95% CI 1.1-16.4, p = 0.03) were significantly associated with these viral hepatitis infections. Intermediate prevalence of HBV and low prevalence of HCV were observed among military personnel. Strengthening HBV screening strategies among military personal may further reduce these viral diseases.


Properties and regulation of C-1-fructose-1,6-diphosphatase from spinach chloroplasts.
Chloroplast fructose diphosphatase (EC 188.8.131.52) was purified according to the procedures of Racker and Schroeder [1] and Buchanan et al. [2] and the properties compared. Neither preparation contained fructose diphosphatase from the cytoplasm. The preparations had similar molecular weights, pH optima, affinites for fructose diphosphate and Mg-2+ and were similarly activated by EDTA, dithiothreitol and cystamine. Mg-2+, fructose diphosphate and dithiothreitol all activate chloroplast fructose diphosphatase more so at suboptimal pH values. The combined effects of these substances under estimated physiological conditions in the chloroplast stroma in the light and in darkness were consistent with almost full activity of the enzyme during illumination but no activity in the dark.


Application of Fourier transform infrared spectroscopy for monitoring hydrolysis and synthesis reactions catalyzed by a recombinant amidase.
This study demonstrates the use of Fourier transform infrared (FTIR) spectroscopy for monitoring both synthesis and hydrolysis reactions catalyzed by a recombinant amidase (EC 188.8.131.52) from Pseudomonas aeruginosa. The kinetics of hydrolysis of acetamide, propionamide, butyramide, acrylamide, benzamide, phenylalaninamide, alaninamide, glycinamide, and leucinamide were determined. This revealed that very short-chain substrates displayed higher amidase activity than did branched side-chain or aromatic substrates. In addition, on reducing the polarity and increasing the substrates' bulkiness, a reduction of the amidase affinity for the substrates took place. Using FTIR spectroscopy it was possible to monitor and quantify the synthesis of several hydroxamic acid derivatives and ester hydrolysis products. These products may occur simultaneously in a reaction catalyzed by the amidase. The substrates used for the study of such reactions were ethyl acetate and glycine ethyl ester. Hydroxylamine was the nucleophile substrate used for the synthesis of acetohydroxamate compounds. Results presented in this article demonstrate the usefulness of FTIR spectroscopy as an important tool for understanding the enzyme structure-activity relationship because it provides a simple and rapid real-time assay for the detection and quantification of amidase hydrolysis and synthesis reactions in situ.


Electrical source imaging of interictal spikes using multiple sparse volumetric priors for presurgical epileptogenic focus localization.
Electrical source imaging of interictal spikes observed in EEG recordings of patients with refractory epilepsy provides useful information to localize the epileptogenic focus during the presurgical evaluation. However, the selection of the time points or time epochs of the spikes in order to estimate the origin of the activity remains a challenge. In this study, we consider a Bayesian EEG source imaging technique for distributed sources, i.e. the multiple volumetric sparse priors (MSVP) approach. The approach allows to estimate the time courses of the intensity of the sources corresponding with a specific time epoch of the spike. Based on presurgical averaged interictal spikes in six patients who were successfully treated with surgery, we estimated the time courses of the source intensities for three different time epochs: (i) an epoch starting 50 ms before the spike peak and ending at 50% of the spike peak during the rising phase of the spike, (ii) an epoch starting 50 ms before the spike peak and ending at the spike peak and (iii) an epoch containing the full spike time period starting 50 ms before the spike peak and ending 230 ms after the spike peak. To identify the primary source of the spike activity, the source with the maximum energy from 50 ms before the spike peak till 50% of the spike peak was subsequently selected for each of the time windows. For comparison, the activity at the spike peaks and at 50% of the peaks was localized using the LORETA inversion technique and an ECD approach. Both patient-specific spherical forward models and patient-specific 5-layered finite difference models were considered to evaluate the influence of the forward model. Based on the resected zones in each of the patients, extracted from post-operative MR images, we compared the distances to the resection border of the estimated activity. Using the spherical models, the distances to the resection border for the MSVP approach and each of the different time epochs were in the same range as the LORETA and ECD techniques. We found distances smaller than 23 mm, with robust results for all the patients. For the finite difference models, we found that the distances to the resection border for the MSVP inversions of the full spike time epochs were generally smaller compared to the MSVP inversions of the time epochs before the spike peak. The results also suggest that the inversions using the finite difference models resulted in slightly smaller distances to the resection border compared to the spherical models. The results we obtained are promising because the MSVP approach allows to study the network of the estimated source-intensities and allows to characterize the spatial extent of the underlying sources.


Phase II Trial of Adjuvant Nivolumab Following Salvage Resection in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck.
Locoregional relapse in patients with head and neck squamous cell carcinoma (HNSCC) is common, approaching 50% for some subsites despite multimodality therapy. Salvage surgery is the standard of care, but able to achieve durable control in only a minority of patients. While adjuvant radiotherapy or chemo-radiotherapy is offered to select patients, this approach can be prohibitively toxic. Given the activity and tolerability of programmed death-1 inhibitors in metastatic HNSCC, we investigated the safety and efficacy of adjuvant nivolumab after salvage surgical resection. This was an open-label, multi-institutional phase II clinical trial (NCT03355560). Patients with recurrent, resectable HNSCC were enrolled within 6 weeks of salvage surgery. Six 28-day cycles of adjuvant nivolumab were planned. The primary endpoint was 2-year disease-free survival (DFS) more than 58%, based on an institutional historical control group of 71 patients with recurrent HNSCC who underwent salvage surgery. Between February 2018 and February 2020, 39 patients were enrolled. At a median follow-up of 22.1 months, 2-year DFS was 71.4% [95% confidence interval (CI), 57.8-88.1] and the 2-year overall survival (OS) was 73% (95% CI, 58-91.8). Three of 39 (8%) patients experienced grade 3 treatment-related adverse events and 3 of 39 (8%) discontinued treatment due to side effects. Ten of 39 had locoregional recurrence, while 2 of 10 also had synchronous metastatic disease. There was no difference in DFS between PD ligand-1 (PD-L1)-positive and PD-L1-negative patients. There was a nonsignificant trend toward improved DFS in patients with high tumor mutational burden (P = 0.083). Adjuvant nivolumab after salvage surgery in locally recurrent HNSCC is well tolerated and showed improved DFS compared with historical controls.


Skin injuries on the body and thigh of dairy cows: associations with season, claw health, disease treatment, and other cow characteristics.
An epidemiological study was conducted in 18 dairy herds with the objective to characterize those groups of cows where skin injuries to the body and thighs occurred most frequently. Data were analyzed with multivariable logistic regression. The epidemiologic patterns were different in first and later lactations. In first lactation some degree of injury occurred among 7.7% of 1793 cows. For most cows occurrence of sole ulcer was positively associated with injury while occurrence of heel horn erosion was negatively associated with injury. The association between injury and body weight differed depending on month of calving (significant interaction). Injuries occurred most frequently among high yielding cows. Severe reproductive, metabolic, and/or infectious diseases were associated with injuries. In later lactations some degree of injury occurred among 13.4% of 832 cows in lactations 2 to 9 where severity of injury increased with lactation number. Injuries occurred least frequently at examinations made in the January to March. They occurred most frequently among cows with sole ulcers. Calving in March through October was associated with injuries especially if the cows were treated for limb disorders. Most cases of injuries occurred early or late in lactation or among high or very low yielding cows in lactations 2 to 9.


Effects of Different Body Positions and Head Elevation Angles on Regional Cerebral Oxygen Saturation in Premature Infants of China.
To investigate the effects of different body positions and head elevation angles on regional cerebral oxygen saturation in premature infants using near-infrared spectroscopy (NIRS). This was a prospective study of premature infants hospitalized. The position was changed each feeding cycle (2-3 h), in order: 15° prone, 15° supine, 0° prone, and 0° supine position. Regional cerebral oxygen saturation (rSO2) was measured after each position period using NIRS, over 7 days. Thirty-three premature infants were included in the analysis. Among them, 22 (66.7%) were male, and 11 (33.3%) were female. When placing the premature infants in the prone position, the regional cerebral oxygen saturation (rSO2) values were higher at head elevation 15° compared with 0° (main effect P < 0.001). When placing the premature infants in the supine position, rSO2 was higher at a head elevation of 15° compared with that at 0° (main effect P < 0.001). When placing the premature infants with a head elevation of 15°, rSO2 in the prone position was higher than that of the supine position (main effect P < 0.001). There was no difference between the prone and supine positions when placing the premature infants with the head elevation at 0° (P > 0.05). Higher cerebral rSO2 can be achieved when placing premature infants in the prone or supine position, with a 15° head elevation angle. Using a specific body position and head angle could improve the regional cerebral oxygen saturation of premature infants.


The effectiveness of routine physiotherapy with and without neuromobilization on pain and functional disability in patients with shoulder impingement syndrome; a randomized control clinical trial.
The objective of the study was to compare the effects of neuromobilization (NM) techniques and routine physiotherapy on pain and functional disability in patients having shoulder impingement syndrome (SIS). Present study was aimed to discover evidence based conservative and cost effective remedy on pain and functional disability. Single blinded randomized control clinical trial. A total of 80 patients with SIS were randomly assigned into care and experimental groups (40 in each group). After the baseline assessment routine physiotherapy was executed on both groups, while NM was applied additionally to experimental group. Pain and functional disability score were evaluated by Visual Analogue Scale and University of California at Los Angeles rating score at baseline, 5th and 11th week. Differences in outcome between groups were evaluated with clinical improvement. The experimental group compared with care group at 11th week had lower mean pain score 2.15(1.66-2.64) vs 4.90(4.41-5.40); between group difference, 1.82; 95% (CI), - 2.38 to - 1.25; P < 0.001 and Partial ƞ2 = 0.33, similarly functional disability score 28.58(27.32-29.83) vs 20.10(18.84-21.36); between group difference,5.62; 95%CI, (4.32-6.92); P< 0.001 and Partial ƞ2 = 0.49 respectively. In experimental group NM was a more effective technique to reduce the pain severity and disability in SIS patients as compare to care group. Neuromobilization techniques in addition to routine physiotherapy were significantly effective for the treatment of SIS. IRCT20190121042445N1 , Registered 19 February 2019.


Coincidental Observation of Global Hypometabolism in the Brain on PET/CT of an AIDS Patient With High-Grade Pulmonary Non-Hodgkin Lymphoma.
AIDS-related dementia complex is the most severe form of cognitive dysfunction in a patient infected with human immunodeficiency virus. The use of FDG PET/CT to diagnose AIDS-related dementia complex has been studied previously and shows various specific metabolic patterns from striatal hypermetabolism in early asymptomatic stage to global hypometabolism in advanced stages. We present a case of a 49-year-old patient with long-standing human immunodeficiency virus infection, where global brain hypometabolism was noted coincidentally on FDG PET/CT done for initial staging of primary pulmonary non-Hodgkin lymphoma.


Antibodies to vasopressin in patients with diabetes insipidus. Implications for diagnosis and therapy.
To determine whether antibodies to vasopressin play a role in the development of diabetes insipidus or interfere with diagnosis and treatment. Random plasma or serum samples for determining of antibodies to vasopressin were collected from patients and controls. Referral university hospital with most patients studied in the clinical research center. Twenty-nine healthy controls and 113 patients with polyuria (15 with primary polydipsia; 86 with neurogenic diabetes insipidus [60 studied before, 28 during, and 10 after antidiuretic hormone treatment]; and 12 with nephrogenic diabetes insipidus). Antibodies were detected by incubating samples with radiolabeled 125I-arginine vasopressin. The effect of antibodies on diagnosis was studied by examining the relation of plasma vasopressin to osmolality measured during dehydration or infusion of hypertonic saline and the relation of urine osmolality to plasma vasopressin measured during dehydration. Antibodies to vasopressin were not detected in patients with primary polydipsia, nephrogenic diabetes insipidus, or neurogenic diabetes insipidus studied before therapy with antidiuretic hormone. Antibodies were detected in 6 of 28 patients studied during such treatments. All 6 patients reported decreased antidiuretic response to previously effective therapy with arginine or lysine vasopressin but had normal response to desmopressin or chlorpropamide. Diabetes insipidus does not result from spontaneously occurring antibodies to vasopressin. The antibodies occasionally develop during treatment with antidiuretic hormone and, when they do, almost always result in secondary resistance to its antidiuretic effect. Antibodies usually do not impair the response to other forms of therapy; they only rarely interfere with the diagnosis of diabetes insipidus, by falsely suggesting the presence of the partial nephrogenic form.


The Early Impact of the COVID-19 Pandemic on Lung, Colorectal, and Breast Cancer Screening and Treatment at a Tertiary Cancer Center.
During the coronavirus-19 pandemic, experts recommended delaying routine cancer screening and modifying treatment strategies. We sought to understand the sequalae of these recommendations. We performed a retrospective single-center analysis of screening, diagnosis, and treatment of lung, colorectal, and breast cancer. Data was collected from our institutional cancer registry. Prepandemic (2016-2019) was compared with pandemic (2020) data. Three thousand three sixty one screening chest computed tomography scans (CTs), 35,917 colonoscopies, and 48,093 screening mammograms were performed. There was no difference in CTs [81.0 (SEM10.0) vs. 65.6 (SEM3.29), P =0.067] or mammograms [1017.0 (SEM171.8) vs. 809.4 (SEM56.41), P =0.177] in 2020 versus prepandemic. There were fewer colonoscopies in 2020 [651.4 (SEM103.5) vs. 758.91 (SEM11.79), P =0.043]. There was a decrease in cancer diagnoses per month in 2020 of lung [22.70 (SEM1.469) vs. 28.75 (SEM0.8216), P =0.003] and breast [38.56 (SEM6.133) vs. 51.82 (SEM1.257), P =0.001], but not colorectal [13.11 (SEM1.467) vs. 15.88 (SEM0.585), P =0.074] cancer. There was no change in stage at presentation for lung ( P =0.717), breast ( P =0.115), or colorectal cancer ( P =0.180). Lung had a shorter time-to-treatment in 2020 [38.92 days (SEM 2.48) vs. 66 (SEM1.46), P =0.002]. In 2020, there was no difference in screening studies for lung and breast cancer but there was a decrease in new diagnoses. Although there were fewer colonoscopies performed in 2020, there was no change in new colorectal cancer diagnoses. Despite changes in guidelines during the pandemic, the time-to-treatment for lung cancer was shorter and was unchanged for colorectal and breast cancer. These findings highlight the importance of continuing care for a vulnerable patient population despite a pandemic.


Between politics and prevention: A re-examination of China's schistosomiasis control campaign in the 1950s.
In the 1950s, China is widely regarded as having made great achievements in the control of schistosomiasis, also known as snail fever. Despite the success, efforts to prevent the disease did not fare well during the Reform period (1978-present). Given this, several key questions need to be addressed. Was the schistosomiasis control campaign a real success in the context of political fervor? Would a schistosomiasis control policy be successful only when it returns to the Maoist medical model, as Miriam Gross argues? Did schistosomiasis return as advertised, or was it never eliminated since the 1950s? In this article, I argue that (1) schistosomiasis control is widely regarded as a great success in an ecological sense, but as far as a long-term mechanism of control is concerned, an approach that relies exclusively on strong political intervention and mass participation may not be effective; (2) schistosomiasis control should first focus on the establishment of a sustainable, long-term mechanism, rather than a temporary, assault-style approach to the problem; and (3) from the 1950s to the present, the spread of schistosomiasis does not represent its return, but, rather, the failure of control efforts to eliminate it.


Educational roles impact burnout in paediatric undergraduate medical educators.
Physician burnout impacts all levels of medical education and has a relatively unknown impact on those responsible for medical student education, particularly in paediatrics. This study examines the prevalence of burnout among paediatric undergraduate medical educators and explores the impact of roles in medical education on medical educator burnout. This cross-sectional mixed-methods study utilised a binational survey of paediatricians involved in undergraduate medical education. Respondents answered demographics, standardised questions about burnout and attitudes towards students, and an open-ended probe about interactions between medical student education and wellness. Of 445 possible, 120 (26.9%) responded to demographic and burnout questions. Of these, 23.3% endorsed burnout, 21.7% high emotional exhaustion (EE) and 10.8% high depersonalisation (DP). High levels of student-related burnout symptoms were reported by fewer than 5% of respondents and were correlated with overall EE and DP. Content analysis revealed four emergent themes: positive effect of student-related role, need to balance medical education and clinical roles, impact of protected time and medical education-related autonomy on educator well-being, and the burden of the administrative portion of educational roles. Participating paediatric educators had low rates of burnout compared with paediatricians as a whole in prior studies. The vast majority found working with students rewarding and described the overall positive impact of their medical education role on wellness. Physician involvement in rewarding non-clinical activities may improve their overall well-being. Providing dedicated time for these activities may ameliorate the difficulty that many medical educators described in balancing their clinical and educational roles. Future studies should continue to explore how we can better support medical educators and the impact of this support on burnout.


Daytime and Nighttime Visual Analog Scales May Be Useful in Assessing Asthma Control Levels Before and After Treatment.
Few questionnaires evaluate daytime and nighttime symptoms separately, although these assessments could contribute to the improvement of disease control levels and prevention of future risks in asthma. The purpose of this retrospective study was to investigate whether daytime and nighttime visual analog scales (VAS) are useful in measuring the perception of symptoms, assessing disease control levels, and evaluating the treatment effects in asthma. Self-reporting asthma control tests (ACT) before and after treatment are standardized tests used to determine disease control levels. A multiple regression analysis was performed to determine the correlation between daytime and nighttime VAS and the characteristics of patients before treatment, as well as the changes in VAS and lung functions and fractional exhaled nitrogen oxide after treatment in 55 treatment-naïve symptomatic adult patients with asthma. Both daytime (r = -0.57, P < 0.0001) and nighttime (r = -0.46, P < 0.0001) VAS correlated well with ACT scores, and there was a correlation between daytime and nighttime VAS (r = 0.33, P = 0.0148) before treatment. In addition, the changes in daytime (r = -0.65, P < 0.0001) and nighttime (r = -0.44, P < 0.0001) VAS were significantly associated with changes in the ACT scores. The multiple regression analysis (β [95% confidence interval]) revealed that improvements in the daytime (-2.33 [-4.55 to -0.11], P = 0.0405) and nighttime (-3.09 [-6.25 to 0.07], P = 0.0505) VAS were associated with an increased forced vital capacity after treatment, although there was no correlation between the VAS and characteristics before treatment. Our study demonstrated that daytime and nighttime VAS were useful in assessing disease control levels and evaluating the treatment effects in asthma.


Therapeutic and functional results of limb salvage to treat sarcomas of the forearm and hand.
Twenty-six patients with soft tissue sarcomas of the forearm and hand were treated with limb salvage protocols involving surgical wide excision, chemotherapy, and radiation therapy. Six received immediate or delayed reconstructive surgery to improve function. The average delay from the time of the first medical consultation until the correct diagnosis was made was 4.5 months. The average follow-up period was 44 months; a 91% survival rate was observed, with an 8% rate of local recurrence. Functional abilities were assessed by a questionnaire concerning work, household activities, and overall satisfaction with the surgical result. Eight-six percent of the patients had an excellent functional result, and 84% reported excellent satisfaction with their operation.


High levels of thrombopoietin in sera of patients with essential thrombocythemia: cause or consequence of abnormal platelet production?
Thrombopoietin (TPO) is the most important regulator of megakaryocyte development and platelet production. Platelet production is thought to be regulated by a negative regulatory feed back loop. In an attempt to evaluate the role of TPO in the pathobiology of essential thrombocythemia (ET), we have examined levels of TPO and other cytokines with thrombopoietic activity (interleukin-6 and interleukin-11) in sera obtained from 25 patients with ET (ten treated, 15 untreated) and 117 healthy control subjects. TPO serum levels were assessed using a sandwich-antibody ELISA that utilizes a polyclonal rabbit antiserum for both capture and signal. The mean serum TPO level in 25 ET patients was significantly elevated (545+/-853 pg/ml) as compared with that in healthy controls (95.3+/-54.0 pg/ml,p<0.001). The difference in TPO serum levels between ten treated (781+/-1229 pg/ ml) and 15 untreated ET patients (388+/-458 pg/ml) did not reach statistical significance (p = 0.09). We conclude that either consumption or production of TPO is altered in ET. Failure of appropriate feedback regulation and continued megakaryocyte stimulation by an elevated TPO may play an important role in the pathobiology of ET.


Costs and complications of equine castration: a UK practice-based study comparing 'standing nonsutured' and 'recumbent sutured' techniques.
Clinicians are often asked to guide owners and trainers over the relative advantages and disadvantages of equine castration performed in either the standing horse with an open unsutured scrotal wound with healing by second intention, or a recumbent horse under general anaesthesia in aseptic conditions, with sutured scrotal skin allowing primary wound closure. To identify types and frequency of complications following the 2 differing approaches, and to compare the financial cost associated with each procedure, based on practice charges. Veterinary expenses of 217 horses castrated by a Newmarket equine veterinary practice over an 18-month period were analysed. Of these, Group 1 (n = 121) were castrated standing and nonsutured by one of 2 ambulatory clinicians and Group 2 (n = 96) castrated in recumbency, in aseptic equine hospital conditions. Group 1 had a complication prevalence of 22% with no mortalities, and Group 2 a significantly lower complication prevalence of 6% (P = 0.001) with a mortality rate of 1%. The financial cost of Group 1, without complications, was approximately one-third of the cost of uncomplicated Group 2. However, the cost of Group 1 with complications increased to approximately two-thirds of the cost of an uncomplicated Group 2 castration. Even though the complication prevalence for Group 1 castrations leaving an open scrotal wound was significantly higher than for a recumbent horse with a sutured scrotal wound in a hospital, the average cost of Group 1 was still less, even taking into account the additional follow-up costs associated with treating such complications. This report provides a benchmark for the outcome of 2 methods of castration based on a database obtained from particular circumstances within the practice involved. Further studies are required to corroborate and take into account future development in surgical and anaesthetic techniques.


Iron cobalt and nitrogen co-doped carbonized wood sponge for peroxymonosulfate activation: Performance and internal temperature-dependent mechanism.
The directional regulation of oxidation capacity in the carbon-based peroxymonosulfate (PMS) activation system is a promising strategy for wastewater purification. In this work, a novel iron cobalt and nitrogen co-doped carbonized wood sponge (FeCoNCWS) was developed. A superb catalytic performance for sulfamethoxazole (SMX) degradation (∼100.0%) was obtained within 30 min in FeCoNCWS800/PMS system at 60 °C. Besides, the reactive oxygen species (ROS) contribution was verified at different reaction temperatures. Specifically, the primary roles of sulfate and hydroxyl radicals (SO4- and OH) in SMX removal weakened, while the secondary role of singlet oxygen (1O2) in SMX degradation was enhanced with the rise of reaction temperature in FeCoNCWS800/PMS system. Interestingly, defects, graphitic N and carbonyl (CO) groups were vital active sites for PMS activation to produce 1O2, which was facilitated at higher reaction temperature. Besides, the metal sites were identified as PMS activators for SO4- and OH generation, which was promoted under lower reaction temperature. The findings revealed a novel internal temperature-dependent PMS activation mechanism, which can help to regulate the oxidation capacity of PMS activation system rationally for pollutant degradation.


Alcohol and pancreatic cancer.
Findings obtained from numerous prospective cohort and case-control studies on alcohol consumption and pancreatic cancer risk have been inconsistent, with many confounding variables present in various investigations. However, heavy alcohol consumption has been known to be a major cause of chronic pancreatitis and a risk factor for type 2 diabetes mellitus, both of which are linked to pancreatic cancer. It has been established that an extensive normal interaction exists between the exocrine and endocrine pancreas, as well as in inflammatory processes and carcinogenesis. Alcohol and its metabolites (acetaldehyde and fatty acid ethyl esters) can alter metabolic pathways involved in the inflammatory response and carcinogenesis, and they are mediated by one or more of the following mechanisms: (1) premature activation of zymogens; (2) induction of the inflammatory response through activation of nuclear transcription factors, including nuclear factor-kappa and activation protein 1; (3) increased production of reactive oxygen species, resulting in oxidative DNA damage and altered effect of dietary antioxidants; (4) activation of pancreatic stellate cells, which leads to fibrosis; (5) gene mutation in enzymes related to cytochrome P450, glutathione S-transferase, aldehyde dehydrogenase, cationic trypsinogen, and pancreatic secretory trypsin inhibitor; (6) synergistic effects of ethanol and tobacco carcinogen on NNK [nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] metabolism; and (7) dysregulation of proliferation and apoptosis. These various metabolic effects of alcohol can lead to or interact with other risk factors (genetic, dietary, environmental, and lifestyle factors) that result in acute and chronic pancreatitis and diabetes mellitus and, ultimately, affect the multistep process of carcinogenesis toward the development of pancreatic cancer.