Modulation of AMPA receptor mediated current by nicotinic acetylcholine receptor in layer I neurons of rat prefrontal cortex.
Layer I neurons in the prefrontal cortex (PFC) exhibit extensive synaptic connections with deep layer neurons, implying their important role in the neural circuit. Study demonstrates that activation of nicotinic acetylcholine receptors (nAChRs) increases excitatory neurotransmission in this layer. Here we found that nicotine selectively increased the amplitude of AMPA receptor (AMPAR)-mediated current and AMPA/NMDA ratio, while without effect on NMDA receptor-mediated current. The augmentation of AMPAR current by nicotine was inhibited by a selective α7-nAChR antagonist methyllycaconitine (MLA) and intracellular calcium chelator BAPTA. In addition, nicotinic effect on mEPSC or paired-pulse ratio was also prevented by MLA. Moreover, an enhanced inward rectification of AMPAR current by nicotine suggested a functional role of calcium permeable and GluA1 containing AMPAR. Consistently, nicotine enhancement of AMPAR current was inhibited by a selective calcium-permeable AMPAR inhibitor IEM-1460. Finally, the intracellular inclusion of synthetic peptide designed to block GluA1 subunit of AMPAR at CAMKII, PKC or PKA phosphorylation site, as well as corresponding kinase inhibitor, blocked nicotinic augmentation of AMPA/NMDA ratio. These results have revealed that nicotine increases AMPAR current by modulating the phosphorylation state of GluA1 which is dependent on α7-nAChR and intracellular calcium.


Regulatory T cell responses: potential role in the control of atherosclerosis.
Atherosclerosis is an inflammatory disease of the arterial wall where both innate and adaptive Th1-driven immunoinflammatory responses contribute to disease development. Th2-related responses have been shown to be either protective or pathogenic. Thus, it is unclear whether immunoregulatory activity can modulate disease development. Novel subtypes of T cells, called the regulatory T cells, have been shown recently to play a critical role in the maintenance of immunological tolerance against self and non-self antigens and prevent the development of various immunoinflammatory diseases. Preliminary studies suggest a potential role for this type of regulatory T cell response in atherosclerosis. Here we present a novel view of the immunoinflammatory response in atherosclerosis where natural and/or adaptive regulatory T cell responses modulate both Th1 and Th2 pathogenic responses and play a central role in counteracting disease initiation and progression.


Role of galeal-pericranial flap in reducing postoperative CSF leak in patients with intracranial endoscopic procedures.
The authors describe a simple technique to reduce the incidence of cerebrospinal fluid (CSF) leak following endoscopic third ventriculostomy and other neuroendoscopic procedures. After the scalp incision, the galea and pericranium are reflected in a single layer after the scalp incision which is then closed in a watertight fashion after the procedure is completed. The securely closed flap prevents minor CSF leaks which would have otherwise required intermittent CSF drainage procedures. This simple procedural modification is effective in children with thin cortical mantle and large ventricles who are otherwise highly susceptible for CSF leak in the postoperative period.


Canonical transient receptor potential channel 2 (TRPC2): old name-new games. Importance in regulating of rat thyroid cell physiology.
In addition to the TSH-cyclic AMP signalling pathway, calcium signalling is of crucial importance in thyroid cells. Although the importance of calcium signalling has been thoroughly investigated for several decades, the nature of the calcium channels involved in signalling is unknown. In a recent series of investigations using the well-studied rat thyroid FRTL-5 cell line, we showed that these cells exclusively express the transient receptor potential canonical 2 (TRPC2) channel. Our results suggested that the TRPC2 channel is of significant importance in regulating thyroid cell function. These investigations were the first to show that thyroid cells express a member of the TRPC family of ion channels. In this review, we will describe the importance of the TRPC2 channel in regulating TSH receptor expression, thyroglobulin maturation, intracellular calcium and iodide homeostasis and that the channel also regulates thyroid cell proliferation.


Requirement of the light-harvesting pigment.protein complex for magnesium ion regulation of excitation energy distribution in chloroplasts.
Cation regulation of excitation energy distribution was examined in chloroplasts isolated from (a) pea seedlings, grown in intermittent illumination, which contain no light-harvesting complex, (b) a barley mutant which is deficient in the major polypeptide component of the light-harvesting complex, and (c) a soybean mutant which contains a reduced amount of light-harvesting complex. It was found that: (1) Mg2+-induced increase in Photosystem II fluorescence at room temperature is small in the chloroplasts of the soybean mutant, smaller in the barley mutant, and almost absent in the light-harvesting complex-less chloroplasts of pea as compared to their respective controls. (2) Mg2+-induced increase in the F685/F730 emission peak ratio at 77 K is not detected in the isolated chloroplasts of the intermittent light-grown pea and the barley mutant. (3) Pre-illumination induced State 1-State 2 and adaptation in vivo is absent in the barley mutant and is less pronounced in the soybean mutant as compared to their respective controls. (4) Increase of slow fluorescence decay upon addition of Mg2+ observed in control chloroplasts was not detected in chloroplasts of intermittent-light grown peas. These results confirm earlier conclusions (Armond, P.A., Arntzen, C.J., Briantais, J.M. and Vernotte, C. (1976) Arch. Biochem. Biophys. 175, 54--63; Davis, D.J., Armond, P.A., Gross, E.L. and Arntzen, C.J. (1976) Arch. Biochem. Biophys. 175, 64--70) that light-harvesting complex is required for the Mg2+-induced regulation of the excitation energy distribution between Photosystems I and II. The characteristic P-S decay and I-D dip of the in vivo fluorescence inductions (Kautsky effect) were not significantly altered in the light-harvesting complex-less and the light-harvesting complex-deficient chloroplasts as compared to their respective controls. These results indicate that light-harvesting complex is not obligatorily required to observe the P-S decay or the I-D dip.


Long-term survival of implant-based oral rehabilitation following maxillofacial reconstruction with vascularized bone flap.
The aim of the study was to assess the 5-year cumulative survival rate of implant-based dental rehabilitation following maxillofacial reconstruction with a vascularized bone flap and to investigate the potential risk factors which might influence the survival rate. A retrospective cohort study was designed. Inclusion criteria involved 18 years old or above patients with the availability of clinical and radiological data and a minimum follow-up 1 year following implant placement. The cumulative survival rate was analyzed by Kaplan-Meier curves and the influential risk factors were assessed using univariate log-rank tests and multivariable Cox-regression analysis. 151 implants were assessed in 40 patients with a mean age of 56.43 ± 15.28 years at the time of implantation. The mean number of implants placed per patient was 3.8 ± 1.3 with a follow-up period of 50.0 ± 32.0 months. The cumulative survival at 1-, 2- and 5-years was 96%, 87%, and 81%. Patients with systemic diseases (HR = 3.75, 95% CI 1.65-8.52; p = 0.002), irradiated flap (HR = 2.27, 95% CI 1.00-5.17; p = 0.05) and poor oral hygiene (HR = 11.67; 95% CI 4.56-29.88; p < 0.0001) were at a significantly higher risk of implant failure. The cumulative implant survival rate was highest at 1st year followed by 2nd and 5th year, indicating that the risk of implant failure increased over time. Risk indicators that seem to be detrimental to long-term survival include poor oral hygiene, irradiated flap and systemic diseases.


Coating thickness affects surface stress measurement of brush electro-plating nickel coating using Rayleigh wave approach.
A surface ultrasonic wave approach was presented for measuring surface stress of brush electro-plating nickel coating specimen, and the influence of coating thickness on surface stress measurement was discussed. In this research, two Rayleigh wave transducers with 5MHz frequency were employed to collect Rayleigh wave signals of coating specimen with different static tensile stresses and different coating thickness. The difference in time of flight between two Rayleigh wave signals was determined based on normalized cross correlation function. The influence of stress on propagation velocity of Rayleigh wave and the relationship between the difference in time of flight and tensile stress that corresponded to different coating thickness were discussed. Results indicate that inhomogeneous deformation of coating affects the relationship between the difference in time of flight and tensile stress, velocity of Rayleigh wave propagating in coating specimen increases with coating thickness increasing, and the variation rate reduces of difference in time of flight with tensile stress increasing as coating thickness increases.


Galactomannan gum coated mucoadhesive microspheres of glipizide for treatment of type 2 diabetes mellitus: In vitro and in vivo evaluation.
Type 2 diabetes mellitus is a heterogeneous disease of polygenic origin and involves both defective insulin secretion and peripheral insulin resistance. Studies have shown that post-meal hyperglycemic spikes are associated with increased cardiovascular mortality in type 2 diabetes. Over the past decade, a major interest in control of postprandial glucose excursion has emerged and a plethora of new medications that specifically target postprandial hyperglycemia were discovered. Despite the availability of new agents for treatment of type 2 diabetes mellitus, oral sulfonylureas remain a cornerstone of therapy, because they are relatively inexpensive and are well tolerated. However, hypoglycemia is a major safety concern with sulfonylureas and it is one major risk factor requiring hospitalization. Glipizide is a potent, rapid-acting with short duration of action and well tolerated second-generation sulfonylurea effective in reducing postprandial glucose levels. However, risk of postprandial hypoglycemia and post-meal glucose excursions, if dose missed before meal; are always associated with the use of glipizide for treatment of type 2 diabetes mellitus. Since, the site of absorption of glipizide is from stomach thus dosage forms that are retained in stomach by mucoadhesion; would increase absorption, improve drug efficiency and decrease dose requirements. Microsphere carrier systems made by using polymer galactomannan having strong mucoadhesive properties and easily biodegradable could be an attractive strategy to formulate. The purpose of this research work is to formulate galactomannan coated mucoadhesive microspheres of glipizide and systematically evaluate its in vitro characteristics and in vivo performance for sustained glucose lowering effect and improvement in diabetic condition as compared to immediate release of glipizide.


Etherolytic cleavage of 4-(2,4-dichlorophenoxy)butyric acid and 4-(4-chloro-2-methylphenoxy)butyric acid by species of Rhodococcus and Aureobacterium isolated from an alkaline environment.
Bacterial strains were isolated from the concrete rubble of a demolished herbicide production plant. The predominant feature of these strains was the etherolytic cleavage of 4-(2,4-dichlorophenoxy)butyric acid (DCPB)1) and 4-(4-chloro-2-methylphenoxy)butyric acid (MCPB) while liberating 2,4-dichlorophenol (DCP) and 4-chloro-2-methylphenol (MCP) respectively. Some of the isolates were identified by 16S rDNA sequence analysis and shown to belong to the genera Aureobacterium sp. (strain K2-17) and Rhodococcus (Rh. erythropolis K2-12). The other strains isolated clustered into these two groups according to fatty acid analysis. Etherolytic cleavage proceeded under neutral to alkaline conditions with an optimum at around pH 8.5. With Aureobacterium sp. No. K2-17, the degradation rate was zero at a pH of 6 but as much as 60% of the maximum activity was observed at pH 10.5. With Rh. erythropolis K2-12, by contrast, pronounced activity was detected at pH 6.5 while degradation was no longer observed at pH 10.5. The maximum rates of cleavage were about 1 mmol DCPB/h.g dry mass with Aureobacterium sp. No. K2-17 and about 0.6 mmol DCPB/h.g dry mass with Rh. erythropolis K2-12. DCPB and MCPB were utilized to the same extent. Substrate cleavage and product formation (DCP) proceeded at almost equal rates with Aureobacterium sp. No. K2-17 and Rh. erythropolis K2-12, which indicates that this compound was not further metabolized. Only phenoxybutyric acid compounds served as substrates; phenoxyacetic acid and phenoxypropionic acid derivatives were not utilized by these strains.


Functional polymorphisms of FAS and FASL gene and risk of breast cancer - pilot study of 134 cases.
Fas/Fas ligand (FasL) system is one of the key apoptotic signaling entities in the extrinsic apoptotic pathway. De-regulation of this pathway, i.e. by mutations may prevent the immune system from the removal of newly-formed tumor cells, and thus lead to tumor formation. The present study investigated the association between -1377 G/A (rs2234767) and -670 A/G (rs1800682) polymorphisms in Fas as well as single nucleotide polymorphisms INV2nt -124 A/G (rs5030772) and -844 C/T (rs763110) in FasL in a sample of Iranian patients with breast cancer. This case-control study was done on 134 breast cancer patients and 152 normal women. Genomic DNA was extracted from whole blood samples. The polymorphisms were determined by using tetra-ARMS-PCR method. There was no significant difference in the genotype distribution of FAS rs2234767 polymorphism between cases and controls. FAS rs1800682, FASL rs5030772, and FASL rs763110 genotypes showed significant associations with an increasing risk of breast cancer (odds ratio OR = 3.18, P = 0.019; OR = 5.08, P = 0.012; OR = 2.40, P = 0.024, respectively). In conclusion, FAS rs2234767 was not associated with breast cancer risk. Though, FAS rs1800682, FASL rs5030772, and FASL rs763110 polymorphisms were associated with the risk of breast cancer in the examined population.


Sequential chemotherapy with cisplatin, leucovorin, and 5-fluorouracil followed by docetaxel in previously untreated patients with metastatic gastric cancer: a phase II study.
The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) has demonstrated a survival advantage over cisplatin and 5-FU, but with substantial hematological toxicity. We aimed to evaluate the efficacy and toxicity of a sequential regimen with cisplatin, leucovorin, and 5-FU (PLF) followed by docetaxel in metastatic gastric cancer patients. Treatment consisted of 4 cycles of biweekly PLF (cisplatin 50 mg/m(2) as a 30-min infusion on day 1, leucovorin 200 mg/m(2) in a 2-h infusion, and 5-FU 2,800 mg/m(2) in a 48-h continuous infusion starting on day 1) followed, in cases of response or stable disease, by 3 cycles of docetaxel (75 mg/m(2), every 3 weeks). Thirty-four patients were enrolled, with an average age of 64 years (range 34-69). The main cumulative grade 3-4 toxicities were: neutropenia (38.2%), febrile neutropenia (11.8%), and fatigue (14.7%). After the planned 7 cycles of treatment, the overall response rate was 38.2% (95% confidence interval [CI] 21.9-54.6), with 3 complete and 10 partial responses. Median progression-free survival and overall survival were 4.8 and 10.6 months, respectively. For patients with metastatic gastric cancer, the sequential administration of cisplatin, leucovorin, 5-FU, and docetaxel may be an effective palliative option and offers a far more favorable toxicity profile than the simultaneous use of docetaxel, cisplatin, and 5-FU.


Effects of accelerated fractionation on radiation injury of the small intestine: a new rat model.
The present study assessed the influence of shortening the overall treatment time (accelerated fractionation) on radiation injury of the small intestine. A rat model which allowed repeated irradiation of a localized segment of small intestine was developed. Young adult male Sprague-Dawley rats were orchiectomized, and a loop of the distal ileum was transposed to the left part of the scrotum. The intestinal segment was irradiated with a total dose of 56 Gy, given in 20 fractions, the total treatment time being either 26, 12, or 7 days (i.e. 1, 2, or 3 fractions per day). Radiation injury was assessed by histopathologic examination at 6 hr and at 2 weeks after the last irradiation. The surgical procedure was without complications. Shortening the overall treatment time by giving more than one radiation dose per day resulted in markedly increased injury both at 6 hr and at 2 weeks. It is concluded that accelerated fractionation results in increased radiation injury of the intestine when compared with standard fractionation. Because there may be a relationship between early and late effects in the intestine, our results also indicate that increased late radiation enteropathy may result from accelerated fractionation.


A Social Desirability Item Response Theory Model: Retrieve-Deceive-Transfer.
In this study, a new item response theory model is developed to account for situations in which respondents overreport or underreport their actual opinions on a positive or negative issue. Such behavior is supposed to be a result of deception and transfer mechanisms. In the proposed model, this behavior is simulated by incorporating a deception term into a multidimensional rating scale model, followed by multiplication by a transfer term, with the two operations performed by an indicator function and a transition matrix separately. The proposed model is presented in a Bayesian framework approximated by Markov chain Monte Carlo algorithms. Through a series of simulations, the parameters of the proposed model are recovered accurately. The methodology is also implemented within an online experimental study to demonstrate the methodology's application.


Soil microbial residue characteristics in Pinus massoniana lamb. Plantations.
A large amount of stable soil organic matter (SOM) is derived from microbial necromass, which can be assessed by quantifying amino sugar biomarkers. Pinus massoniana Lamb. Plantations are widely distributed in China and play a vital role in forest carbon sequestration. However, the patterns of soil microbial residue remain poorly understood. In this study, amino sugars were used to characterize patterns of soil microbial residues at three soil depths (0-10, 10-20, and 20-30 cm) in P. massoniana plantations of different ages (young, middle-aged, near-mature, mature, and over-mature; denoted as YG, MD, NM, MT, and OM, respectively). In the topsoil (0-10 cm), the total nitrogen (TN) content of the OM forest was the highest, whereas the soil organic carbon (SOC) content of the MT forest was the highest. Consistent with changes in SOC and TN, total microbial residue content decreased with increasing soil depth. However, the total microbial residues C to SOC contribution increased considerably with increasing depth, suggesting that more SOC was derived from microbial residues in the subsoil than that from the topsoil. The fungal residue C to SOC contribution was higher than that of bacterial residue C. Total amino sugar content in the topsoil increased with increasing age, and MT and OM had a significantly higher content than that of other forests. At all soil depths, SOC and TN content predominantly determined microbial necromass, whereas soil microbial biomass content predominantly determined microbial necromass in the topsoil; soil pH predominantly determined microbial necromass in the 10-20 cm soil layer; and soil pH and Ca2+ content were the primary factors in the soil layer below 20 cm. The study provides valuable insights into controls of microbial-derived organic C could be applied in Earth system studies for predicting SOC dynamics in forests.


Portable Infrared Isothermal PCR Platform for Multiple Sexually Transmitted Diseases Strand Detection.
Rapid and portable PCR detection is essential for screening sexually transmitted infections regularly. We developed an infrared mediated RNA isothermal RT-PCR (IR-MERIT PCR) platform and its compatible multichamber microfluidic chip for simultaneous amplification and testing (SAT) detection. This microfluidic chip integrates RNA extraction, micropump, and multitarget detection function onto the same chip. By utilizing IR-light-emitting diode (LED) as heat source, this platform can fulfill isothermal amplification within 70 min.


Clustering of mitoses in human cervical carcinoma.
Mitotic nests have been noted both in tissue culture (Cone, 1968) and in human skin (Rowe and Dixon, 1975). The present paper is concerned with the disposition of mitoses in human tumor tissue. Mitotic indices, cell counts, and mitotic clusters were recorded in 20 carcinomas of the cervix uteri. The significance of the results was verified statistically. In 18 of 20 biopsies, the clustering of mitoses was in excess of chance at the 95% confidence level. Assuming a chance distribution, one would expect only one case (5% of 20 cases) to show significant clustering of mitoses. The incidence of cases which show mitotic clustering is higher in cervical carcinoma than in normal skin and uninvolved skin of psoriatic patients. The clustering phenomenon might be due to an initiating factor derived from a mitotic cell which propagates to other cells and activates them, or to a local deficiency in inhibitor factors which reversibly inhibit mitoses under normal conditions.


[Acupuncture for back pain: meta-analysis of randomised controlled trials and an update with data from the most recent studies].
Acupuncture is commonly used to treat back pain. A meta-analysis of clinical trials of acupuncture for this condition came to a positive conclusion whilst a qualitative review was negative. To compare our meta-analysis of trials of acupuncture for the treatment of back pain with a qualitative review and the most recent studies on the subject. A systematic literature search was conducted to retrieve all randomised controlled trials of any form of acupuncture for any type of back pain in humans. The adequacy of the acupuncture was assessed by consulting six experienced acupuncturists. The main outcome measure for the meta-analysis was numbers of subjects who where improved at the end of treatment. These data are discussed in relation to the qualitative review and the most recent studies. Twelve studies were included of which nine presented data suitable for meta-analysis. The odds ratio of improvement with acupuncture compared with control intervention was 2.30 (95% confidence interval 1.28 to 4.13). For sham-controlled, evaluator-blinded studies, the odds ratio was 1.37 (95% confidence interval, 0.84-2.25). The results from the majority of the most recent studies also support the effectiveness of acupuncture in the treatment of back pain. Collectively, these data imply that acupuncture is superior to various control interventions, although there is insufficient evidence to state whether it is superior to placebo.


Lattice dynamics of BaFe2Se3.
This paper presents a study of the lattice dynamics in BaFe2Se3. We combined first-principle calculations, infrared measurements and a thorough symmetry analysis. Our study confirms thatPnmacannot be the space group of BaFe2Se3, even at room temperature. The phonons assignment requiresPmto be the BaFe2Se3space group, not only in the magnetic phase, but also in the paramagnetic phase at room temperature. This is due to a strong coupling between a short-range spin-order along the ladders, and the lattice degrees of freedom associated with the Fe-Fe bond length. This coupling induces a change in the bond-length pattern from an alternated trapezoidal one (as inPnma) to an alternated small/large rectangular one. Out of the two patterns, only the latter is fully compatible with the observed block-type magnetic structure. Finally, we propose a complete symmetry analysis of the BaFe2Se3phase diagram in the 0-600 K range.


Apolipoprotein E allele frequencies in a South African Indian female population.
Coronary heart disease is common amongst South Africans of Indian (Asian) ancestry. As part of an investigation into risk factors in premenopausal and post-menopausal Indian nurses, we determined the apolipoprotein E genotype by means of restriction isotyping on 173 healthy nurses between the ages of 25-55 years. The apolipoprotein E allele frequencies on 346 chromosomes were: epsilon 2, 1.2% (95% confidence interval 0.06-2.66); epsilon 3, 87.6% (95% confidence interval 84.1-91.1 and epsilon 4, 11.3% (95% confidence interval 7.94-14.60). No epsilon 2/2 homozygotes were encountered. Our results demonstrate an extremely low frequency of the epsilon 2 allele, a low-normal apo epsilon 4 and a high epsilon 3 allele frequency. It is unlikely that apolipoprotein E polymorphism contributes to the high incidence of coronary heart disease in this population.


Zinc transport in pregnancy.
Although the importance of zinc nutrition during pregnancy has been well recognized, there have been few studies of zinc transport in maternal or fetal sera. We examined total serum zinc levels as well as zinc associated with its major transport proteins, albumin and alpha 2-macroglobulin, prospectively in 46 women during gestation and in 27 of their infants at term. In five women who developed preeclampsia during the third trimester, the mean total serum zinc level at 6 to 14 weeks was decreased by 14% compared to control values (p less than 0.05). Fetomaternal differences between the zinc transport proteins support the concept that each may have a specific role(s) in zinc homeostasis which is regulated to a greater extent by metabolic factors than by dietary zinc intake alone.


Adaptive and incidental consequences of the alba polymorphism in an agricultural population of Colias butterflies: female size, fecundity, and differential dispersion.
A sex-limited color dimorphism occurs in many populations of Colias eurytheme. Alba females exhibit different patterns of resource allocation and are less attractive than orange females. This study examines some of the consequences of these differences in terms of reproductive success and population structure in a high density agricultural population.Alba females produced more eggs than orange females on a daily basis, but the morphs did not differ in three measures of size. Spermatophore counts revealed that fresh and worn females did not differ in mating frequency between the two morphs, but very worn alba females gained more matings than very worn orange females.In two mark-release-recapture experiments, alba females exhibited longer residence times than orange females. Changes in population structure over time suggest that this was due to dispersal of orange females from the mature field. Evidence is presented that orange females emigrate in response to male harassment at high density while alba females, exposed to less harassment, remain behind. We suggest that the persistence of the polymorphism in this agricultural population is at least partially facilitated by the cyclic cutting of the alfalfa.


Genitoanal injury in adult female victims of sexual assault.
To evaluate the presence and extFent of genitoanal injury among sexually assaulted women and to estimate the risk of injury in subgroups according to the type of assault and to the sexually assaulted women's susceptibility to injury. A case-control study of 249 women exposed to sexual assault. Injury identified by gross visualization. Women with and without injury were compared. Logistic regressions analyses were performed to calculate the risk of injury. Thirty-two percent sustained genitoanal injury. Anal penetration and assaults on women without prior sexual experience were associated with genitoanal injury. Most women do not have visible genitoanal injuries. The risk of sustaining genitoanal injury during a sexual assault is higher among women without prior sexual intercourse experience and among women exposed to anal penetration. The severity of the assault is a poor predictor of genitoanal injury.


Novel mutations in ZP1, ZP2, and ZP3 cause female infertility due to abnormal zona pellucida formation.
The human zona pellucida (ZP) is an extracellular glycoprotein matrix composed of ZP1, ZP2, ZP3, and ZP4 surrounding the oocyte, and it plays an important role in sperm-egg interactions during fertilization. Structural and functional changes in the ZP can influence the process of fertilization and lead to female infertility. Previous studies have identified mutations in ZP1, ZP2, and ZP3 that lead to female infertility caused by oocyte degeneration, empty follicle syndrome, or in vitro fertilization failure. Here we describe seven patients from six independent families who had several abnormal oocytes or suffered from empty follicle syndrome, similar to the previously reported phenotypes. By whole-exome sequencing and Sanger sequencing, we identified several novel mutations in these patients. These included three homozygous mutations in ZP1 (c.1708G > A, p.Val570Met; c.1228C > T, p.Arg410Trp; c.507del, p.His170Ilefs*52), two mutations in a compound heterozygous state in ZP1 (c.1430 + 1G > T, p.Cys478X and c.1775-8T > C, p.Asp592Glyfs*29), a homozygous mutation in ZP2 (c.1115G > C, p.Cys372Ser), and a heterozygous mutation in ZP3 (c.763C > G, p.Arg255Gly). In addition, studies in CHO cells showed that the mutations in ZP1, ZP2, and ZP3 might affect the corresponding protein expression, secretion, and interaction, thus providing a mechanistic explanation for the phenotypes. Our study expands the spectrum of ZP gene mutations and phenotypes, and provides a further understanding of the pathogenic mechanism of ZP gene mutations in vitro.


α-Gal A missense variants associated with Fabry disease can lead to ER stress and induction of the unfolded protein response.
Anderson-Fabry Disease (FD) is an X-linked lysosomal disorder caused by mutations in GLA, the gene encoding the lysosomal hydrolase α-galactosidase A (α-Gal A), leading to accumulation of glycosphingolipids in the lysosomes. FD is a multisystemic disorder leading to progressive cardiovascular, cerebrovascular and kidney dysfunction. Phenotypes are divided in two main classes, classic or non-classic, depending on substrate accumulation, age at onset, disease manifestation, severity and progression. The more severe classical phenotype is generally associated with mutations leading to absent or strongly reduced α-Gal A activity, while mutations with higher residual activity generally lead to the non-classical one. Approximately 70% of the over 1,000 Fabry disease-associated mutations are missense mutations, some leading to endoplasmic reticulum (ER) retention of mutant protein. We hypothesized that such mutations could be associated, besides the well-known absence of α-Gal A function/activity, to a possible gain of function effect due to production of a misfolded protein. We hence expressed α-Gal A missense mutations in HEK293 GLA -/- cells and investigated the localization of mutant protein and induction of ER stress and of the unfolded protein response (UPR). We selected a panel of 7 missense mutations, including mutants shown to have residual or no activity in vitro. Immunofluorescence analysis showed that mutants with residual activity have decreased lysosomal localization compared with wild type, and partial retention in the ER, while missense mutants with no residual activity are fully retained in the ER. UPR (ATF6 branch) was significantly induced by all but two mutants, with clear correlation with the extent of ER retention and the predicted mutation structural effect. These data identify a new molecular pathway, associated with gain of function effect, possibly involved in pathogenesis of FD.


Exploring physician agency under demand-side cost sharing-An experimental approach.
The assumption of patient-regarding physicians has been widely adopted in the health economics literature. Physicians' patient-regarding preferences are often described as the concern for the health benefits of medical treatments, and thus closely related to the norms and ethics of the medical profession. In this paper, we ask whether physicians' patient-regarding preferences include a concern for their patient's consumption opportunities alongside patient's health benefits. To identify and quantify physicians' preferences, we design and conduct an incentivized laboratory experiment where choices determine separately the health benefits and the consumption opportunities of a real patient admitted to the nearest hospital. We find strong evidence that future physicians care about their patients' consumption opportunities.


Post-process treatments are effective strategies to reduce Listeria monocytogenes on the surface of leafy greens: A pilot study.
Growth of L. monocytogenes is among the most important factors affecting the risk of human listeriosis. In ready to eat leafy greens, the use of anti-Listeria treatments represents a good alternative to inhibit growth during storage. Several commercially available antimicrobial agents have been suggested as effective intervention strategies. Among them, phage preparations and bacteriocin-producing strains have shown promising results against L. monocytogenes. In this study, we investigate the efficacy of two commercially available surface treatments, the bacteriophage formulation PhageGuard Listex (Micreos Food Safety B.V., NL) and the bacteriocin-producing culture SafePro® (CHR Hansen, DK) to inactivate L. monocytogenes in fresh-cut curly endive after processing and during storage. Fresh-cut endive was inoculated with a cold-adapted L. monocytogenes cocktail of 6 strains (4.4 ± 0.0 log cfu/g) and treated with the anti-Listeria treatments. The treatments were applied using a spray system at two different places within the processing line, on the conveyor belt and in the centrifuge. A total of 5 different treatments were applied: i) Untreated (CT); ii) PhageGuard Listex on the conveyor belt (Listex_Conveyor); iii) PhageGuard Listex during centrifugation (Listex_Centrifuge); iv) SafePro on the conveyor belt (SafePro_Conveyor); and v) SafePro during centrifugation (SafePro_Centrifuge). Samples were stored 3 days at 5 °C plus 5 days at 8 °C. PhageGuard Listex treatment reduced L. monocytogenes in fresh-cut endive by 2.5 logs, regardless of the place of treatment application (conveyor belt or centrifuge). On the other hand, SafePro only reduced L. monocytogenes by 0.2 and 0.4 logs, at the conveyor belt and centrifuge, respectively. Maximum L. monocytogenes reductions of about 3.5 log units were observed in fresh-cut endive treated with PhageGuard Listex after 3 days of storage. At the end of the shelf life (8 days), the initial trends were maintained and the fresh-cut curly endive treated with PhageGuard Listex showed the lowest L. monocytogenes concentration. However, by the end of the shelf-life, L. monocytogenes showed higher levels (1.3-fold) than immediately after the application of the treatment. One hypothesis could be that L. monocytogenes cells, which were able to survive the anti-Listeria treatments, were also able to proliferate under the specific storage conditions. Based on the obtained results, PhageGuard Listex seems to be a promising decontamination agent for leafy greens aiming to reduce growth of the bacteria but further work is needed.


Determination of prednisolone in human adipose tissue incubation medium using LC-MS/MS to support the measurement of 11beta-hydroxysteroid dehydrogenase activity.
A method for the determination of prednisolone in human adipose tissue incubation medium has been developed, validated and used to support studies designed to measure the activity of 11beta-hydroxysteroid dehydrogenase in human adipose tissue. After incubation, samples (80 microL) were extracted using Oasis HLB microElute SPE plates and the resulting extracts were analyzed using reversed-phase chromatography coupled to an Applied Biosystems Sciex PE API-4000 mass spectrometer with a TurboIonSpray interface (400 degrees C). The method was validated over the calibration range of 0.5-100 ng/mL. Intraday precision and accuracy were 6.1% R.S.D. or less and within 6.3%, respectively. Interday precision and accuracy were 4.2% R.S.D. or less and within 3.6%, respectively. Extraction recovery of prednisolone was greater than 84% over the range of low to high quality control sample concentrations. The validated assay was used to support studies designed to estimate ex vivo 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) enzyme activity in human adipose tissue.


Laparoscopic appendectomy and cholecystectomy during pregnancy: six case reports.
Pregnancy was once considered a contraindication to laparoscopic cholecystectomy and appendectomy. The progression of laparoscopic techniques has resulted in a continued reassessment of laparoscopic procedures during pregnancy. There still exists some controversy as to the safety of laparoscopic procedures during pregnancy. This paper reviews our series of six pregnant patients treated laparoscopically for appendicitis and cholecystitis. Charts were reviewed of all pregnant patients who underwent laparoscopic cholecystectomy or appendectomy at St Clare's Hospital Schenectady, New York between 1992 and 1996. Six patients were identified. Patients and obstetricians were contacted to investigate the results of the pregnancy. All patients and fetuses survived the procedure. Two patients delivered prematurely but remote from the operative procedure. All infants were healthy postpartum. One patient underwent an elective abortion as she had planned. The abortion was remote from the surgical procedure. Our series adds to the growing evidence that laparoscopic cholecystectomy and laparoscopic appendectomy can be performed safely during pregnancy.


Topical delivery of urea encapsulated in biodegradable PLGA microparticles: O/W and W/O creams.
This study describes the formulation and characterization of O/W and W/O creams containing urea-loaded microparticles prepared with poly (D, L-lactic-co-glycolic acid) (PLGA) in order to encapsulate and stabilize urea. The solvent evaporation method was used for preparing PLGA microparticles containing urea. The microparticles size was evaluated by laser light diffractometry. The resulting microparticles were then incorporated in O/W and W/O creams and stability and the release pattern from the creams was evaluated by UV-spectrophotometry. The particle size of PLGA microparticles was in the range of 1-5 microm and most microparticles had a particle size smaller than 3 microm. The encapsulation efficiency was calculated as 40.5% +/- 3.4. This study also examined release pattern of urea which varied among different formulations. The results showed that the release from O/W creams followed Higuchi kinetics while the release from W/O creams showed the zero order kinetics and the creams containing microparticulated urea had slower release than free urea creams.


Fertility Preservation in Adolescents with Klinefelter Syndrome is Experimental but May Increase Therapeutic Options for Biological Paternity.
While approximately half of adult Klinefelter syndrome (KS) patients have retrievable sperm on micro testicular sperm extraction, success is limited by testicular hyalinization beginning at puberty. Recent surgical and laboratory advances lend themselves to experimental fertility preservation in appropriately selected adolescent KS patients.


Regional brain IR-Met-, IR-Leu-enkephalin concentrations during progress and full electrical amygdaloid kindling.
Using amygdaloid kindling in chronic rats, we were able to observe behavioral, electrographic and IR-Met- and IR-Leu-enkephalin changes throughout the progress of different stages of convulsive activity. Rats presenting the initial stages of kindling, rats presenting the first generalized motor seizure, and rats with at least 10 generalized seizures were sacrificed 24 h after the last stimulus; also rats with at least 10 generalized seizures but sacrificed 21 days after the last seizure were compared with control and sham-operated groups of rats. The IR-Met and IR-Leu enkephalin concentrations in each group were measured in the striatum, amygdala, hypothalamus, medulla oblongata (including pons), hippocampus, mid-brain, spinal cord and cerebral cortex. A progressive increase in IR-Leu-enkephalin in amygdala and hippocampus was observed over the course of kindling. These increases remained until 21 days after rats were fully kindled (at least 10 generalized seizures). We observed increased and decreased concentration of each peptide in different regions. We discussed the regional and the differential effects of each peptide. The increased concentrations in limbic structures were associated with the amygdaloid increased excitability through the kindling process. We suggest that the decreases in concentrations are related with structures involved in the output behavior manifestations produced by kindling stimulation.


Complement activity and pharmacological inhibition in cardiovascular disease.
While complement is the most important component of humoral autoimmunity, and inflammation plays a key role in atherosclerosis, relatively few studies have looked at complement implications in atherosclerosis and its complications. C-reactive protein is a marker of inflammation and is also involved in atherosclerosis; it activates complement and colocalizes with activated complement proteins within the infarcting myocardium and the active atherosclerotic plaques. As new agents capable of modulating complement activity are being developed, new targets for the management of atherosclerosis are emerging that are related to autoimmunity and inflammation. The present paper reviews the putative roles of the various complement activation pathways in the development of atherosclerosis, in ST segment elevation and non-ST segment elevation acute coronary syndromes, and in coronary artery bypass graft surgery. It also provides a perspective on new therapeutic interventions being developed to modulate complement activity. These interventions include the C1 esterase inhibitor, which may be consumed in some inflammatory states resulting in the loss of one of the mechanisms inhibiting activation of the classical and lectin pathways; TP10, a recombinant protein of the soluble complement receptor type 1 (sCR1) which inhibits the C3 and C5 convertases of the common pathway by binding C3b and C4b; a truncated version of the soluble complement receptor type 1 CRI lacking the C4b binding site which selectively inhibits the alternative pathway; and pexelizumab, a monoclonal antibody selectively blocking C5 to prevent the activation of the terminal pathway that is involved in excessive inflammation and autoimmune responses.


Is a portable accelerometer-based navigation system useful in total hip arthroplasty?: A systematic review and meta-analysis.
Precise implant alignment is a crucial prognostic factor for successful outcomes following total hip arthroplasty (THA). A portable accelerometer-based navigation (PN) device may achieve the same accuracy as that achieved by the computer-assisted navigation surgery technique, with the convenience of a conventional technique. Although the usefulness of PN in THA (PN-THA) has been reported, whether it is more accurate than performing THA with a conventional technique (CON-THA) remains controversial. The difference in surgical time between PN-THA and CON-THA is also unclear. Therefore, we conducted a systematic review and meta-analysis of studies comparing results of PN-THA with those of CON-THA. We focused on the following question: is PN-THA superior to CON-THA in terms of radiological parameters and surgical time? A literature search was conducted in PubMed, Web of Science, and Cochrane Library, to identify studies that met the following inclusion criteria: randomised controlled trials (RCT) or non-RCT, studies involving patients who underwent PN-THA and patients who underwent CON-THA, studies including data on radiological parameters and surgical outcomes. Author names, publication year, country, study design, surgical approach, demographic characteristics of the participants (diagnosis, gender, age, and body mass index), and surgical outcomes (the radiological parameters and the surgical time) were extracted. We calculated the mean differences (MDs) for continuous data with 95% confidence intervals (CIs) for each outcome. p<0.05 was considered significant. Three studies were included in this meta-analysis. The meta-analysis showed that absolute deviation of the postoperative measured angles from the target position for the cup anteversion was significantly smaller in PN-THA than in CON-THA (MD=-1.70, 95% CI=-2.91 to -0.50, [p=0.005]). There was no significant difference in the absolute deviation of the postoperative measured angles from the target position for cup abduction between the groups (MD=-1.82, 95% CI=-4.32-0.67, [p=0.15]). The surgical time was significantly longer in PN-THA than in CON-THA (MD=8.58, 95% CI=4.05-13.10, [p=0.0002]). This systematic review and meta-analysis of studies comparing the results of PN-THA with those of CON-THA showed that the PN-THA is advantageous for precise cup implantation compared to CON-THA, although PN-THA has a longer surgical time compared to CON-THA. III.


Impact of 18F-FDG-PET/CT on the management of Staphylococcus aureus bacteraemia: a retrospective observational study.
To assess the impact of 18F-FDG-PET/CT on the diagnosis and management of patients with Staphylococcus aureus bacteraemia (SAB). Post hoc analysis of a prospective cohort of consecutive adult patients diagnosed with SAB (January 2013-December 2017). Patients who underwent 18F-FDG-PET/CT at the discretion of the attending physician were included. Endpoints were the identification of previously unknown infectious foci and changes in clinical management, defined as changes in the duration or class of antibiotic therapy, a surgical procedure on the source of infection or a change in the decision to remove or retain an implantable device. We included 39 patients (median age: 69 years, IQR:60-79). Fifteen (39%) patients did not have an infectious focus identified before 18F-FDG-PET/CT). Thirty new infectious foci were detected in 22/39 (56%) patients. In 11/15 (73%) patients without an identified focus at least one infectious focus was detected by 18F-FDG-PET/CT. In 22/26 (85%) patients with implantable devices, 18F-FDG-PET/CT confirmed or ruled out infection or detected local complications. Out of 13 device infections, 10 were detected by 18F-FDG-PET/CT (7/10 for the first time). In 19/39 (49%) patients 18F-FDG-PET/CT results led to changes in clinical management (15 changes in antibiotic therapy, 2 device removals, 2 surgical procedures, 1 avoidance of a surgical procedure). 18F-FDG-PET/CT may be a useful asset in the management of selected SAB cases, allowing the identification of previously undetected infectious foci and optimization of therapy, particularly in patients with endovascular devices. Indication should be made on a case-by-case basis.


Evidence for rapid faunal changes on islands in a man-made lake : I. Ants.
Few studies of island biogeography have been made on islands in which the time of insularization is precisely known. We tested the effects of island formation on ant species diversity in a man-made lake in South Africa, to determine whether island effects are detectable after only 16 years of insularization. The number of ant species observed at trap-line censuses on islands was significantly correlated with island size (r=0.608; P<0.05) and ant species diversity was generally low compared with similar mainland habitats. Mean species number for all islands, including landbridge islands, was 5.5±3.3 species, and on mainland sites was 7.9±2.85 species. Island effects were more marked on islands <20 ha, which had a mean of 3.3±2.5 species per island. Species number on islands was inversely related to densities of the aggressive Anoplolepis custodiens and A. steingroeveri. These two species were only patchily distributed on mainlands, but these ants were nearly ubiquitous on small islands. Several lines of evidence suggest that this single species domination may be responsible for island effects. Island sites also differed in the number of ant species in different trophic groupings, tending to have fewer granivorous species than the mainland sites, but species in other diet groups were similar in both island and mainland habitats. We conclude that there have been marked changes in the ant faunas on islands smaller than 20 ha apparently due to changes in abundance of the dominant ant species. However, the causes of these changes are unknown.


Long-term deficiency of essential fatty acids in rats and its effect on brain recovery.
1. Nineteen-day old rats were fed an essential fatty acid deficient diet for 37 weeks, thereby making them essential fatty acid deficient for at least 24 weeks. The weights of their brains were 33% less than those of rats on control diets. 2. When the deficient rats were rehabilitated for ten weeks on a diet containing 5% by weight corn oil as a source of essential fatty acids, the weights of their brains were still 30% less than those of the controls. 3. Analysis of the brain lipids showed that, there was a large reduction in the proportions of cerebrosides and sphingomyelin in essential fatty acid deficiency. 4. Essential fatty acid deficiency was also characterised by the appearance of a high proportion of eicosatrienoic acid (20:3) and the reduction of arachidonic acid (20:4) and the other essential fatty acids. 5. Rehabilitation for a period of 10 weeks did not reverse these changes in brain composition. 6. It is considered that the feeding of essential fatty acid deficient diet to rats for a prolonged period of time causes retardation of brain maturity and makes the brain resistant to later dietary manipulations.


Hairy cell leukemia: Past, present and future.
This brief review highlights the sequence of therapeutic milestones and advances in our understanding of the biology of hairy cell leukemia (HCL) with a focus on recent molecular findings and how these may be applied to improve disease outcomes in the future. Targeted therapy is discussed in the context of the recently identified BRAF mutation and other genetic findings.


Swelling rather than shrinkage precedes apoptosis in serum-deprived vascular smooth muscle cells.
Contrasting cell volume behaviours (swelling vs. shrinkage) are considered as criteria to distinguish necrosis from apoptosis. In this study, we employed a time-lapse, dual-image surface reconstruction technique to assess the volume of single vascular smooth muscle cells transfected with E1A-adenoviral protein (E1A-VSMC) and undergoing rapid apoptosis in the absence of growth factors or in the presence of staurosporine. After 30- to 60-min lag-phase, serum-deprived E1A-VSMC volume was increased by ~40%, which preceded maximal increments of caspase-3 activity and chromatin cleavage. Swollen cells underwent rapid apoptotic collapse, documented by plasma membrane budding, and terminated in 10-15 min by the formation of numerous apoptotic bodies. Suppression of apoptosis by inhibition of Na(+),K(+)-ATPase and activation of cAMP signalling with ouabain and forskolin, respectively, completely abolished the swelling of serum-deprived E1A-VSMC. In contrast to serum deprivation, apoptotic collapse of staurosporine-treated E1A-VSMC preceded attenuation of their volume by ~30%. Neither transient hyposmotic swelling nor isosmtotic shrinkage triggered apoptosis. Our results show that cell shrinkage can not be considered as ubiquitous hallmark of apoptosis. The involvement of stimulus-specific cell volume perturbations in initiation and progression of apoptosis in vascular smooth muscle cells should be examined further.


Technologically enhanced total knee replacement: is the juice worth the squeeze?
The purpose of this article is to outline the limb alignment goals for knee replacement, current surgical technologies, and evidence-based medicine principles regarding technologically advanced total knee arthroplasty (TKA). Radiologists need an understanding of the pros and cons of technologically advanced TKA. At this time, the appropriate role for TKA has not been determined.


Acute exacerbation of idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive and ultimately fatal disease, the clinical course of which in individual patients is highly variable. Sudden deterioration of a patient's respiratory condition during a stable course is not uncommon. Many cases of uncertain etiology have been called acute exacerbation (AEx) of IPF, under the assumption of sudden acceleration of the underlying disease process. In recent years, several studies have reported the clinical significance of AEx-IPF. In 2007 Collard and colleagues created a Consensus Perspective, which proposed consensus definition and standard diagnostic criteria. This review primarily discusses studies performed after this Consensus Perspective.


The Characteristics of Human iPS Cells and siRNA Transfection Under Hypoxia.
The characteristics of pluripotent cells have great potential for basic and clinical research and application. We describe the effect of normoxia or hypoxia regarding the proliferation and pluripotency of human iPS cells using colony number counting and real-time polymerase chain reaction (PCR). In addition, the function of hypoxia-inducible factors (HIFs) in human iPS cells under hypoxic conditions is evaluated in relation to the expression of pluripotency markers by siRNA and real-time PCR. Furthermore, we introduce the change of HIF-2α expression when signal transducer and activator of transcription 3 (STAT3) is suppressed by its inhibitor, Stattic or S31 201, using RT-PCR.


A quality assurance tool for helical tomotherapy using a step-wedge phantom and the on-board MVCT detector.
The purpose of this study was to develop and evaluate filmless quality assurance (QA) tools for helical tomotherapy by using the signals from the on-board megavoltage computed tomography (MVCT) detector and applying a dedicated step-wedge phantom. The step-wedge phantom is a 15 cm long step-like aluminum block positioned on the couch. The phantom was moved through the slit beam and MVCT detector signals were analyzed. Two QA procedures were developed, with gantry fixed at 0°: 1) step-wedge procedure: to check beam energy consistency, field width, laser alignment with respect to the virtual isocenter, couch movement, and couch velocity; and 2) completion procedure: to check the accuracy of a field abutment made by the tomotherapy system after a treatment interruption. The procedures were designed as constancy tool and were validated by measurement of deliberately induced variations and comparison with a reference method. Two Hi-Art II machines were monitored over a period of three years using the step-wedge procedures. The data acquisition takes 5 minutes. The analysis is fully automated and results are available directly after acquisition. Couch speed deviations up to 2% were induced. The mean absolute difference between expected and measured couch speed was 0.2% ± 0.2% (1 standard deviation SD). Field width was varied around the 10 mm nominal size, between 9.7 and 11.1 mm, in steps of 0.2 mm. Mean difference between the step-wedge analysis and the reference method was < 0.01 mm ± 0.03 mm (1 SD). Laser (mis)alignment relative to a reference situation was detected with 0.3 mm precision (1SD). The step-wedge profile was fitted to a PDD in water. The PDD ratio D20/D10, measured at depths of 20 cm and 10 cm, was used to check beam energy consistency. Beam energy variations were induced. Mean difference between step-wedge and water PDD ratios was 0.2% ± 0.3% (1SD). The completion procedure was able to reveal abutment mismatches with a mean error of -0.6 mm ± 0.2 mm (1SD). The trending data over a period of three years showed a mean deviation of 0.4% ± 0.1% (1 SD) in couch speed. The spread in field width was 0.15 mm (1 SD). The sagittal and transverse lasers showed a variation of 0.5 mm (1 SD). Beam energy varied 1.0% (1 SD). A mean abutment mismatch was found of -0.4 mm ± 0.2 mm (1 SD) between interrupted treatments. The on-board MVCT detector, in combination with the step-wedge phantom, is a suitable tool for a QA program for helical tomotherapy. The method allowed frequent monitoring of machine behavior for the past three years.


Novel hydrogels as supports for in vitro cell growth: poly(ethylene glycol)- and gelatine-based (meth)acrylamidopeptide macromonomers.
Conversion of amine groups with vinyl-functional azlactones occurs at room temperature under physiological conditions to afford (meth)acrylamidopeptide-functional macromonomers. Such macromonomers based upon alpha,omega-bisaminopropyl-terminated poly(ethylene glycol) and gelatine were prepared and copolymerized to produce novel hydrogel networks. Compression modulus was inversely proportional to the water content (EWC), which was controlled primarily by the PEG macromonomers with non-modified gelatine, the covalent attachment of gelatine to the hydrogel network gave substantially improved performance with respect to both, adhesion and growth of human fibroplasts.


Signal transduction pathway of nitric oxide inducing PC12 cell death.
To study signal transduction pathway of nitric oxide inducing death of PC12 cells. Cell survival rate was measured with MTT assay, and caspase-3 activity with caspase-3 assay kits after PC12 cells were incubated with sodium nitroprusside (SNP), caspase-3 inhibitor II plus SNP or p38 inhibitor-SB203580 plus SNP. SNP induced death of PC12 cells in dose- and time-dependent manner and enhanced caspase-3 activity gradually. Both caspase-3 inhibitor II and SB203580 reduced cell death, but SB203580 reduced caspase-3 activity significantly. NO may induce death of PC12 cells through activation of p38 and caspase-3.


[Effect of high viral hepatitis B virus DNA loads on vertical transmission of hepatitis B virus in late-pregnant women].
To investigate the effect of high viral loads (HBV DNA concentration in blood > 2.0 copy/ml) on the vertical transmission of hepatitis B virus in mothers with HBV DNA positivity. Forty pregnant women with HBV DNA positivity were divided randomly, double-blindly into 2 groups: at 28 weeks of pregnancy, one group received oral lamivudine (100 mg/d) and the other received oral placebo. The serum HBV DNA loads were tested at 28 and 40 weeks' gestation in mothers, and serum HBV DNA,HBsAg, HBeAg and anti-HBs were examined in infants at 12 month follow up. Thirty-nine infants finished (one twins) the follow up, and 2 infants lost (5%). Among them 4 infants were confirmed to be HBV infection (10%, 4/39), 2 in the treatment group (10%, 2/20) and 2 in the control group (11%, 2/19) (P > 0.05). The serum HBV DNA levels of 40 weeks' gestation in the treatment group, compared with the levels of 28 weeks' gestation in the treatment group and 40 weeks' gestation in the control group, showed a significant decline (P < 0.01). The HBV DNA levels of the mothers whose infants were infected, were (3.1 +/- 3.4) copy/ml, (3.1 +/- 3.2) copy/ml during 28 and 40 weeks' gestation, and for mothers whose infants were non-infected, the levels were (3.4 +/- 2.2) copy/ml, (2.6 +/- 1. 5) copy/ml respectively (P > 0.05). The mean values of anti-HBs of 18 infants in the treatment group showed no significant difference as compared to 17 infants in the control group, (594 +/- 416) U/L vs (458 +/- 398) U/L (P > 0.05). The pregnant women's HBV DNA loads could be obviously decreased from high viral loads (HBV DNA concentrations in blood > 2.0 copy/ml) after they take lamivudine from 36 weeks' gestation. But it might not reduce the maternal-fetal vertical transmission of HBV infection.


Semi-batch synthesis of colloidal spheres with fluorinated cores and varying grafts of poly(ethylene glycol).
Fluorinated spheres with grafted poly(ethylene glycol) (PEG) have been synthesized using a semi-batch emulsion polymerization in which the initiator is fed slowly to the reaction. In this way, PEG-grafted colloidal spheres can be fabricated with varying PEG chain length, different cores and varying degrees of crosslinking. The resulting batches have been characterized using disc centrifuge photosedimentometry and small-angle X-ray scattering. The size distribution is shown to be a sensitive function of the molar ratio of the reactive PEG macromonomer to fluorinated monomer, and with some optimization latices of very low polydispersity can be obtained with this simple synthesis method. For short PEG grafts too high a molar ratio results in a build up of smaller size particles and a broadening of the size distribution, whereas for longer grafts the mean particle size increases with decreasing molar ratio.


Exogenous DNA enhances DUOX2 expression and function in human pancreatic cancer cells by activating the cGAS-STING signaling pathway.
Pro-inflammatory cytokines upregulate the expression of the H2O2-producing NADPH oxidase dual oxidase 2 (DUOX2)2 which, when elevated, adversely affects survival from pancreatic ductal adenocarcinoma (PDAC). Because the cGAS-STING pathway is known to initiate pro-inflammatory cytokine expression following uptake of exogenous DNA, we examined whether activation of cGAS-STING could play a role in the generation of reactive oxygen species by PDAC cells. Here, we found that a variety of exogenous DNA species markedly increased the production of cGAMP, the phosphorylation of TBK1 and IRF3, and the translocation of phosphorylated IRF3 into the nucleus, leading to a significant, IRF3-dependent enhancement of DUOX2 expression, and a significant flux of H2O2 in PDAC cells. However, unlike the canonical cGAS-STING pathway, DNA-related DUOX2 upregulation was not mediated by NF-κB. Although exogenous IFN-β significantly increased Stat1/2-associated DUOX2 expression, intracellular IFN-β signaling that followed cGAMP or DNA exposure did not itself increase DUOX2 levels. Finally, DUOX2 upregulation subsequent to cGAS-STING activation was accompanied by the enhanced, normoxic expression of HIF-1α and VEGF-A as well as DNA double strand cleavage, suggesting that cGAS-STING signaling may support the development of an oxidative, pro-angiogenic microenvironment that could contribute to the inflammation-related genetic instability of pancreatic cancer.


Spatio-temporal analysis of socio-economic characteristics for pulmonary tuberculosis in Sichuan province of China, 2006-2015.
The disease burden caused by pulmonary tuberculosis (TB) in Sichuan province still persisted at a high level, and large spatial variances were presented across regional distribution disparities. The socio-economic factors were suspected to affect the population of TB notification, we aimed to describe TB case notification rate (CNR) and identify which factors influence TB epidemic are necessary for the prevention and control of the disease in Sichuan province. A retrospective cross-sectional study and an ecological spatial analysis was conducted to quantify the presence and location of spatial clusters of TB by the Moran's I index and examined these patterns with socio-economic risk factors by hierarchical Bayesian spatio-temporal model. A total of 630,009 pulmonary TB cases were notified from 2006 to 2015 in 181 counties of Sichuan province. The CNR decreased year by year since 2007, from 88.70 to 61.37 per 100,000 persons. The spatial heterogeneities of CNR were observed during the study periods. Global Moran's I index varied from 0.23 to 0.44 with all P-value < 0.001. The Bayesian spatio-temporal model with parametric spatio-temporal interactions was chosen as the best model according to the minimum of Deviance Information Criterion (DIC)(19,379.01), and in which the quadratic form of time was taken. The proportion of age group and education year were all associated with CNR after adjusting the spatial effect, temporal effect and spatio-temporal interactions. TB CNR increased by 10.2% [95% credible interval (CI): 6.7-13.7%] for every 1-standard-deviation increase in proportion of age group and decreased by 23% (95% CI: 13.7-32.7%) for every 1-standard-deviation increase in education year. There were spatial clusters of TB notification rate in Sichuan province from 2006 to 2015, and heavy TB burden was mainly attributed to aging and low socioeconomic status including poor education. Thus, it is more important to pay more attention to the elderly population and improve socioeconomic status including promoting education level in Sichuan province to reduce the TB burden.


Pan-cancer clinical and molecular analysis of racial disparities.
Racial disparities in cancer outcomes are increasingly recognized, but comprehensive analyses, including molecular studies, are limited. The objective of the current study was to perform a pan-cancer clinical and epigenetic molecular analysis of outcomes in African American (AA) and European American (EA) patients. Cross-platform analyses using cancer databases (the Surveillance, Epidemiology, and End Results program database and the National Cancer Data Base) and a molecular database (The Cancer Genome Ancestry Atlas) were performed to evaluate clinical and epigenetic molecular differences between AA and EA patients based on genetic ancestry. In the primary pan-cancer survival analysis using the Surveillance, Epidemiology, and End Results database (2,045,839 patients; 87.5% EA and 12.5% AA), AA patients had higher mortality rates for 28 of 42 cancer types analyzed (hazard ratio, >1.0). AAs continued to have higher mortality in 13 cancer types after adjustment for socioeconomic variables using the National Cancer Database (5,150,023 patients; 11.6% AA and 88.4% EA). Then, molecular features of 5,283 tumors were analyzed in patients who had genetic ancestry data available (87.2% EA and 12.8% AA). Genes were identified with altered DNA methylation along with increased microRNA expression levels unique to AA patients that are associated with cancer drug resistance. Increased miRNAs (miR-15a, miR-17, miR-130-3p, miR-181a) were noted in common among AAs with breast, kidney, thyroid, or prostate carcinomas. The current results identified epigenetic features in AA patients who have cancer that may contribute to higher mortality rates compared with EA patients who have cancer. Therefore, a focus on molecular signatures unique to AAs may identify actionable molecular abnormalities.


Estrogens and cell death in murine uterine luminal epithelium.
The luminal epithelium of adult ovariectomized mice responds to estradiol-17 beta with a synchronised wave of DNA synthesis and mitosis. Estriol, however, although producing a similar DNA-synthetic and mitotic response fails to cause an increase in cell number owing to a wave of cell death occurring at mitosis. In the present study it was shown that cells died by two different routes. The majority died by apoptosis but, unusually, a minority also died by necrosis. In the apoptotic cells the cytoplasm became dense, the endoplasmic reticulum and nuclear cisternae dilated; chromatin became marginated the nucleus shrank and became deeply infolded and contorted. Apoptosis, however, was uncharacteristic in that the nucleus failed to fragment, form caps or show disruption before the cells died by membrane rupture. Furthermore, the cells were frequently lost in sheets from the epithelium into the lumen. Part of the biochemical explanation for this onset of cell death comes from the accelerated loss from the tissue of estriol when compared to estradiol-17 beta. This resulted in a decline in protein and rRNA biosynthesis and a failure to complete ribosomal maturation. Evidence in favour of this explanation came from experiments that showed a return to the estradiol-17 beta level of response and an inhibition of cell death when the occupancy of the estriol receptor was maintained.


[Lung function testing in patients with pulmonary arterial hypertension].
The main objective was to describe the results of lung function testing in a series of 120 patients with pulmonary arterial hypertension, and the secondary objective was to compare these findings with hemodynamic variables. This was a descriptive study of lung function in 120 patients with stable pulmonary arterial hypertension (Evian/Venice groups 1 and 4) studied until January 2002 in the Pulmonary Hypertension and Lung Transplant Working Group attached to the Cardiology Department of the Hospital Universtario 12 de Octubre in Madrid, Spain. Data were collected retrospectively for the first 47 patients (1981 to 1995) and prospectively thereafter for the remaining 73 patients. The diagnosis was idiopathic arterial hypertension or hypertension associated with collagenosis, chronic pulmonary embolism, cardiac shunt, or toxic oil syndrome (30 cases). In the group as a whole, forced vital capacity, forced expiratory volume in 1 second, and total lung capacity were normal; mean (SD) values revealed low carbon dioxide diffusing capacity (67.6% [23.2%]), and moderate hypoxemia (65.8 [15.4] mm Hg). No significant associations were observed between lung function and hemodynamic parameters. Mean age in the toxic oil syndrome group was lower (33.7 [11.4] years), and these patients had higher mean scores on the New York Heart Association scale (3.3 [0.5]) and for pulmonary vascular resistance (20.3 [8.1] kPa.L(-1).s). Lung function was studied in a series of 120 patients with pulmonary arterial hypertension (Evian/ Venice groups 1 and 4), 30 of whom had toxic oil syndrome. No significant associations were found between lung function and hemodynamic parameters.


Exploring the impact of online and offline teaching methods on the cognitive abilities of medical students: a comparative study.
Online education has become increasingly popular, but research on the effectiveness of different teaching models in developing cognitive skills is limited. This study investigated the relationship between different teaching models (online and offline) and the development of cognitive skills in clinical medicine students. Survey data were collected from 2018 entry students who participated in online teaching and 2019 entry students in offline teaching at Xiangya School of Medicine, Central South University. National Quality Open Courses (NQROC) were provided to both groups of students. The study examined the total score of physiology final exam, score of each type of question, and NQROC learning engagement in different score segments under the two teaching models. Non-parametric statistical methods were utilized to analyze the total score of physiology final exam, score of each type of question, and the NQROC learning engagement. Spearman's rank correlation was utilized to analyze the relationship between the score of physiology final exam and the students' NQROC learning engagement. The study found no statistically significant difference in the total score, short-answer questions (SAQs) score, and case study questions (CSQs) score between online and offline teaching models. However, the multiple-choice questions (MCQs) score was higher in the online teaching model (Z=-4.249, P < 0.001), suggesting that online teaching may be an effective way to improve lower-order cognitive skills among students. In contrast, low-achieving students had higher total scores (Z=-3.223, P = 0.001) and scores in both MCQs (Z=-6.263, P < 0.001) and CSQs (Z=-6.877, P < 0.001) in the online teaching model. High-achieving students in the online teaching model had higher total scores (Z=-3.001, P = 0.003) and MCQs scores (Z=-5.706, P < 0.001) but lower scores in CSQs (Z=-2.775, P = 0.006). Furthermore, students' NQROC learning engagement was greater in the online teaching model. The results of this study suggested that online teaching was not statistically significantly different from offline in cognitive domains and was more desirable than offline in strengthening lower-order cognitive skills. However, it was important to note that offline teaching may be more effective in reinforcing higher-order cognitive skills among high-achieving students. In conclusion, this study provided important insights into the effectiveness of different teaching models in developing cognitive skills among medical students and highlighted the potential benefits of online teaching in enhancing students' lower-order cognitive skills.


Detection of coregulation in differential gene expression profiles.
Genomics and proteomics approaches generate distinct gene expression and protein profiles, listing individual genes embedded in broad functional terms as gene ontologies. However, interpretation of gene profiles in a regulatory and functional context remains a major issue. Elucidation of regulatory mechanisms at the gene expression level via analysis of promoter regions is a prominent procedure to decipher such gene regulatory networks. We propose a novel genetic algorithm (GA) to extract joint promoter modules in a set of coexpressed genes as resulting from differential gene expression experiments. Algorithm design has focused on the following constraints: (I) identification of the major promoter modules, which are (II) characterized by a maximum number of joint motifs and (III) are found in a maximum number of coexpressed genes. The capability of the GA in detecting multiple modules was evaluated on various test data sets, analyzing the impact of the number of motifs per promoter module, the number of genes associated with a module, as well as the total number of distinct promoter modules encoded in a sequence set. In addition to the test data sets, the GA was evaluated on two biological examples, namely a muscle-specific data set and the upstream sequences of the beta-actin gene (ACTB) derived from different species, complemented by a comparison to alternative promoter module identification routines.


Microwave-activated Cu-doped zirconium metal-organic framework for a highly effective combination of microwave dynamic and thermal therapy.
Percutaneous microwave ablation (PMA) is a thermoablative method used as a minimally invasive treatment for liver cancer. However, the application of PMA is limited by its insufficient ROS generation efficiency and thermal effects. Herein, a new microwave-activated Cu-doped zirconium metal-organic framework (MOF) (CuZr MOF) used for enhanced PMA has a significantly improved microwave sensitizing effect. Owing to the strong inelastic collisions between ions confined in numerous micropores, CuZr MOF has strong microwave sensitivity and high thermal conversion efficiency, which can significantly improve microwave thermal therapy (MTT). Moreover, because of the existence of Cu2+ ions, a further benefit of CuZr MOF is their Fenton-like activity, in particular, microwaves used as an excitation source for microwave dynamic therapy (MDT) can improve the Fenton-like reaction to maximize the synergistic effectiveness of cancer therapy. Importantly, CuZr MOF can inhibit the production of heat shock proteins (HSPs) by producing abundant ROS to enhance tumor destruction. Mechanistically, we found that CuZr MOF + MW treatment modulates ferroptosis-mediated tumor cell death by targeting the HMOX1/GPX4 axis. In summary, this study develops a novel CuZr MOF microwave sensitizer with great potential for synergistic treatment of liver cancer by MTT and MDT.


Perspectives on long-acting formulations of pre-exposure prophylaxis (PrEP) among men who have sex with men who are non-adherent to daily oral PrEP in the United States.
Pre-exposure prophylaxis (PrEP) persistence among men who have sex with men (MSM) in real world clinical settings for HIV prevention is suboptimal. New longer-acting formulations of PrEP are becoming available, including injectables, subdermal implants, and other oral medications. These longer-acting formulations have the potential to improve retention among those who have challenges remaining adherent to daily oral PrEP. We interviewed 49 MSM who had initiated but discontinued oral PrEP at three diverse clinics across the United States. We examined participants' perspectives about long-acting PrEP formulations and how long-acting options could affect PrEP use using thematic analysis. Participants were not very knowledgeable about long-acting formulations of PrEP but were open to learning about them and considering use. Participants were concerned about safety and efficacy of products given that they were still newer and/or in development. Finally, participants had clear preferences for oral pills, injectables, and then subdermal implants and were most interested in options that reduced the number of visits to the clinic. Long-acting formulations of PrEP are acceptable to MSM with suboptimal PrEP persistence and have the potential to improve PrEP persistence. However, many felt they needed more information on safety, efficacy, and use to consider these options. As these long-acting formulations are implemented, public health campaigns and clinical interventions to encourage may maximize uptake particularly among those who are not currently adherent to daily oral PrEP.


Comparison of adsorption behavior studies of methylene blue by microalga residue and its biochars produced at different pyrolytic temperatures.
The adsorption behaviors of methylene blue (MB) on microalga residue powder (MRP) and biochars derived from microalga residue (MRB) produced at different pyrolytic temperatures were compared. Six biochars were prepared from residual Chlorella sp. and Spirulina sp. at different pyrolytic temperatures in the range of 200-550 °C. The adsorption kinetics, isotherms, thermodynamics, and the effect of pH were studied, and chemical analyses of MB-loaded MRP and MRB were conducted using SEM, FTIR, and XPS techniques. The results found that the pseudo-second-order, Elovich, and Freundlich models could effectively describe the MB adsorption process on MRP and MRB. The thermodynamic results confirmed that the adsorption processes were spontaneous and endothermic. Further, MRP showed an excellent adsorption ability on MB through electrostatic interaction, complexation with oxygen/nitrogen-containing functional groups and π-π interaction. However, massive oxygen-containing functional groups after pyrolysis were lost, leading to a significant decrease in the adsorption capacity of MRB on MB. This phenomenon was further observed with increasing pyrolytic temperature. Overall, this study demonstrated that microalga residue performed better for MB removal compared with their pyrolyzed analogs. Graphical abstract.


Lethal neonatal Menkes' disease with severe vasculopathy and fractures.
A male neonate presented with an acute onset of severe intra-abdominal bleeding, haemorrhagic shock and multiple fractures leading to death on d 27. Menkes' disease was diagnosed at autopsy and confirmed by copper accumulation studies on cultured fibroblasts. Such an early onset of fatal complications in this condition has not been previously reported. New insights into the pathogenesis of Menkes' disease provided by DNA mutation analysis and difficulties in neonatal diagnosis are discussed. Menkes' disease should be considered in male infants with pathological fractures and other signs of connective tissue disease, even in the neonatal period.


Direct visual or blind insertion of the primary trocar.
We set out to assess the difference in complication rates between primary umbilical insertion by a blind trocar and insertion with an optical surgical obturator. In a retrospective survey, we investigated the rate of severe complications by primary umbilical trocar entry. Of 1546 patients undergoing gynecological laparoscopies at a tertiary-care university hospital, 1000 cases were operated by blind umbilical insertion with a conventional primary trocar whereas 546 used an optical primary trocar. The rate of major complications during insertion of the primary trocar in the blind insertion group was five of 1000 (0.5%), whereas there were no major complications in the optical-guided insertion group (0.0%). In comparison with the blind insertion of a sharp trocar, optical guidance provides a safe and functional primary insertion method that allows to detect adhesions to be detected at an early stage, thus preventing injuries to the bowel and abdominal vessels.


History of Dorsal Preservation Surgery: Seeking Our Historical Godfather(s) for the "Push Down" and "Let Down" Operations.
There are 2 approaches for lowering the osseocartilaginous nasal dorsum. The most frequently used method includes resection of the osseocartilaginous nasal dorsum. The second method is based on preservation of the osseocartilaginous nasal dorsum. The concept of dorsal preservation surgery is to preserve, not resect, the nasal bones and upper lateral cartilage. Reduction rhinoplasty with preservation of the nasal dorsum is not only possible, but results in a natural appearing postoperative dorsal esthetic line. Thus, the rhetorical question: Why reconstruct the nasal dorsum when you can simply preserve it?


Clinical outcomes of 3D conformal hypofractionated single high-dose radiotherapy for one or two lung tumors using a stereotactic body frame.
This study was performed to evaluate the clinical outcomes of three-dimensional (3D) conformal hypofractionated single high-dose radiotherapy for one or two lung tumors using a stereotactic body frame. Forty patients who were treated between July 1998 and November 2000 and were followed for >10 months were included in this study. Of the 40 patients, 31 had primary lung cancer and 9 had metastatic lung cancer. The primary lung cancer was staged as T1N0M0, T2N0M0, and T3N0M0 in 19, 8, and 4 patients, respectively. The primary sites of metastatic lung cancer were the colon in 4, tongue in 2, and osteosarcoma, lung cancer, and hepatocellular carcinoma in 1 each. 3D treatment planning was performed to maintain the target dose homogeneity within 15% and to decrease the irradiated lung volume from >20 Gy to <25%. All patients were irradiated using a stereotactic body frame and received 4 times 10-12 Gy single high-dose radiation at the isocenter during a period of 5-13 days (median 12). The initial 3 patients received 40, and the remaining 37 patients received 48 Gy after dose escalation. Of the 33 tumors followed >6 months, 6 tumors (18%) disappeared completely after treatment. Twenty-five tumors (76%) decreased in size by 30% or more after treatment. Therefore, 31 tumors (94%) showed a local response. During the follow-up of 4-37 months (median 19), no pulmonary complications greater than National Cancer Institute-Common Toxicity Criteria Grade 2 were noted. Of the 16 patients with histologically confirmed T1N0M0 primary lung cancer who received 48 Gy, all tumors were locally controlled during the follow-up of 6-36 months (median = 19). In 9 tumors with lung metastases that were irradiated with 48 Gy in total, 2 tumors did not show a local response. Finally, 3 tumors (33%) with lung metastases relapsed locally at 6-12 months (median 7) after treatment during the follow-up of 3-29 months (median 18). 3D conformal hypofractionated single high-dose radiotherapy of 48 Gy in 4 fractions using a stereotactic body frame was useful for the treatment of lung tumors.


Utility of rapid tests to assess the prevalence of indicator organisms (Aerobic plate count, Enterobacteriaceae, coliforms, Escherichia coli, and Listeria spp.) in apple packinghouses.
The 2014 listeriosis outbreak caused by caramel-coated apples was linked to apples cross-contaminated within an apple packing facility. This outbreak has increased the focus on effective cleaning and sanitation methods that must be validated and monitored during apple packing. Thus, rapid and reliable testing methods are necessary for assessing cleanliness in the apple packing industry. The objectives of this study were to assess the prevalence of common indicator organisms [Aerobic plate count (APC), Enterobacteriaceae, coliforms, Escherichia coli, and Listeria spp.] on food contact surfaces (zone 1) in apple packinghouses and to evaluate the utility and accuracy of currently used rapid tests (ATP and glucose/lactose residue swabs). Food contact surfaces were sampled over a 100 cm2 area in five commercial apple packinghouses to evaluate populations of indicator organisms APC, Enterobacteriaceae, coliforms, E. coli (n = 741), and rapid test readings (n = 659). Petrifilm plates were used for the quantification of APC, Enterobacteriaceae, and coliform/E. coli. Rapid tests [ATP swabs (UltraSnap) and glucose/lactose residue swabs (SpotCheck Plus)] were processed on-site. A larger area (0.93 m2) was sampled for the detection of Listeria spp. (n = 747), following a modified protocol of the FDA's Bacteriological Analytical Manual method, and confirmed with PCR and gel electrophoresis via the iap gene. No significant association was found between either rapid test and populations of APC, Enterobacteriaceae, coliforms, E. coli, and Listeria spp. detection. However, recovery of APC (log CFU/100 cm2) was higher with a failed glucose/lactose residue swab surface hygiene result (3.1) than a passed result (2.9) (p = 0.03). Populations of APC, Enterobacteriaceae, and coliforms were significantly different at each unit operation during the packing process (p ≤ 0.05). This study concluded that ATP and glucose/lactose residue rapid tests were poorly suited for determining microbial load since they were not related to populations of any common indicator organisms or the detection of Listeria spp. These findings emphasize the need to utilize a rapid test, which can be a good indicator of residual matter on a surface, along with traditional microbiological methods to assess cleaning and sanitation practices in apple packinghouses.


Congenital diaphragmatic hernia: an evaluation of the prognostic value of the lung-to-head ratio.
A retrospective analysis of the prognostic significance of the lung-to-head ratio (LHR) on the outcome of fetuses with left-sided congenital diaphragmatic hernia (CDH). A total of 12 fetuses with isolated left CDH without any chromosomal abnormalities were included in this study. Twelve LHR measurements could retrospectively be calculated from the last available ultrasonographic recordings before birth. The relationship between the LHR and fetal outcome and gestational age was investigated. The cutoff levels as previously published were applied to determine their predictive value in this population. The association between other prenatal predictive variables and the fetal outcome was also determined. Survival was defined as being discharged from the hospital. The overall survival rate was 75%, and a statistically significant difference was observed between the mean LHR of the survivors and the mean LHR of the nonsurvivors (1.81 vs. 0.43), whereas the mean gestational age of these two groups did not differ. The LHR was not gestational age dependent with regard to its ability to predict the fetal outcome. The cutoff levels LHR <1, 1-1.4, and >1.4 showed good applicability for predicting fetal outcome within the present study population, with 100% survival if LHR >1.4 and 75% mortality if LHR <1. The intrathoracic position of the stomach, mediastinal shift, and polyhydramnios as individual variables and early diagnosis (<25 weeks gestation) all turned out to be poor sonographic predictors of fetal outcome. The LHR proved to be a good predictor of fetal outcome, independent of gestational age at the time of measurement. To further substantiate our observations, a prospective multicenter study is warranted.


Anti-inflammatory activity of flavonol glycosides from Erythrospermum monticolum depending on single or repeated local TPA administration.
Two anti-inflammatory principles were isolated from the methanol extract of the leaves of Erythrospermum monticolum (Flacourtiaceae). The isolation was based on a guided bioassay of the inhibitory activity on TPA-induced ear edema in mice. These compounds were identified as quercetin 3-O-xylosyl(1-->2) rhamnoside and quercetin 3-O-rhamnoside. In addition, their effects on a chronic topic inflammation model were evaluated.


Glomerular Disease in Temporal Association with SARS-CoV-2 Vaccination: A Series of 29 Cases.
Immune responses to vaccination are a known trigger for a new onset of glomerular disease or disease flare in susceptible individuals. Mass immunization against SARS-CoV-2 in the COVID-19 pandemic provides a unique opportunity to study vaccination-associated autoimmune kidney diseases. In the recent literature, there are several patient reports demonstrating a temporal association of SARS-CoV-2 immunization and kidney diseases. Here, we present a series of 29 cases of biopsy-proven glomerular disease in patients recently vaccinated against SARS-CoV-2 and identified patients who developed a new onset of IgA nephropathy, minimal change disease, membranous nephropathy, ANCA-associated GN, collapsing glomerulopathy, or diffuse lupus nephritis diagnosed on kidney biopsies postimmunization, as well as recurrent ANCA-associated GN. This included 28 cases of de novo GN within native kidney biopsies and one disease flare in an allograft. The patients with collapsing glomerulopathy were of Black descent and had two APOL1 genomic risk alleles. A brief literature review of patient reports and small series is also provided to include all reported cases to date (n=52). The incidence of induction of glomerular disease in response to SARS-CoV-2 immunization is unknown; however, there was no overall increase in incidence of glomerular disease when compared with the 2 years prior to the COVID-19 pandemic diagnosed on kidney biopsies in our practice. Glomerular disease to vaccination is rare, although it should be monitored as a potential adverse event.


What Is the Role of Allergic Contact Dermatitis in Patients with Lower Leg Ulcers?
To analyze the relationship between contact dermatitis and delayed wound healing, discuss the diagnosis and treatment of lower leg contact dermatitis, and provide an algorithm for the patient with a red leg and delayed wound healing. This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. After participating in this educational activity, the participant will:1. Describe the nature of contact dermatitis.2. Distinguish between allergic and irritant contact dermatitis and the other major differential diagnoses of delayed wound healing in this clinical scenario.3. Outline the steps in the diagnosis of allergic contact dermatitis and irritant contact dermatitis and identify common haptens responsible for allergic contact dermatitis in patients with venous leg ulcers.4. Apply the algorithm for delayed wound healing on a background of lower leg dermatitis.


Prox-1 and VEGFR3 antibodies are superior to D2-40 in identifying endothelial cells of lymphatic malformations--a proposal of a new immunohistochemical panel to differentiate lymphatic from other vascular malformations.
We previously reported that D2-40 antibody identifies lymphatic endothelial cells (LECs) of lymphatic malformations (LM) with high specificity but only moderate sensitivity. The aim of this study was to compare the sensitivity and specificity of the markers Prospero-related homeobox gene-1 (Prox-1) and VEGFR3 to those of D2-40 for LECs in LM. Seventeen LM and 6 other vascular malformations with venous component (VM) were stained with D2-40, Prox-1, VEGFR3, CD31, and CD34 antibodies. The staining characteristics of vessels by each marker were assessed. Prox-1 and VEGFR3 specificity for LECs was examined by endothelial staining of VMs. Prox-1 and VEGFR3 stained substantially more large vessels than did D2-40 (15 of 17 cases). Small vessel staining was uniformly positive with all vascular markers except CD34, which did not stain lymphatic vessels. Eight cases had no or minimal D2-40 staining of large vessels, but the selected D2-40-vessels stained positive with VEGFR3, and 7 of 8 vessels were Prox-1 positive. Nine cases had variable D2-40 staining of large vessels; the selected D2-40 channels were all Prox-1 positive, and 8 of 9 were VEGFR3 positive. Two had rare vascular channels with no lymphatic marker stain but were positive for CD31 and CD34. Endothelial cells of VM had no Prox-1 but were VEGFR3/CD31/CD34 positive. VEGFR3 and Prox-1 antibodies have greater sensitivity for large lymphatic vessels than does D2-40. All lymphatic markers have high sensitivity for LECs of small lymphatic channels. Prox-1 has superior sensitivity and specificity to LECs. We recommend utilizing an immunohistochemical panel consisting of Prox-1, VEGFR3, CD31, and CD34 antibodies to differentiate lymphatic from venous malformations in pathologic practice.


Experience gained from operation of 103 adrenal incidentalomas.
Adrenal incidentaloma poses a perplexing problem for physicians. The challenge is to identify the rare functioning or malignant adrenal tumor that should be removed. From 1970 until December 1996, we managed 579 patients with adrenal hyperplasia or neoplasm. Of these, 110 were followed without any operation and 469 were operated on. The histology from the operated patients revealed 145 pheochromocytomas, 72 Cushing's syndrome, 98 aldosteronomas, 21 virilizing tumors, 3 feminizing tumors, 98 non-functioning adrenalomas, 17 metastases, 7 cysts, and 15 miscellaneous tumors. Among the 98 non-functioning adrenal tumors, 79 were incidentalomas. Histological examination of 103 operated incidentalomas found 55 adenomas (5 functioning=aldosteronomas), 12 benign pheochromocytomas, 3 malignant or suspicious pheochromocytomas, 8 cystic lymphangiomas, 4 metastases, 4 angiomas, 3 ganglioneuromas, 4 myelolipomas, 1 hyperplasia, 2 hematomas, 2 cysts, and 5 adreno-cortical carcinomas. Among the non-operated incidentalomas, the most frequent findings were adenomas, metastases, hematomas, cysts and pseudotumoral hyperplasia; three disappeared spontaneously. No patients died of unrecognized adrenocortical carcinoma. Our experience confirms that in case of incidentaloma, the first concern is a nonfunctional pheochromocytoma (15%), and the less common occurrence is adreno-cortical carcinoma (2%). We recommend a restrictive surgical approach in the setting of adrenal incidentalomas.


Antigen recognition in the pathogenesis of immunoglobulin A-related autoimmune bullous diseases.
Immunoglobulin A (IgA) is the most common subtype of antibodies in mucosal surfaces. In most of autoimmune bullous diseases, however, immunoglobulin G (IgG) is the main pathogenic antibody that plays a role through complementation. The IgA antibody for epidermal connection protein can be found in the sera of some patients with blistering skin disease. Of these patients, some have the IgA antibody in their sera, while others have IgG and IgA antibodies. IgA-related autoimmune bullous diseases are less common in clinical practice. In the past, these diseases were not fully understood and their classifications were confusing. Recently, some progress has been made in the study of these diseases.


Phase II trial of vindesine and VP16-213 in the palliation of poor-prognosis patients and elderly patients with small cell lung cancer.
Forty-three previously untreated patients, all of whom had poor-prognosis small cell lung cancer and/or were greater than 65 years old, received treatment with vindesine and VP16-213. Thirteen patients had limited disease and 30 extensive disease. Response rates (CR + PR) of 86% (CR 29%) and 66% (CR 17%) were seen in patients with limited and extensive disease, respectively. Time to relapse was short in those responding (4-4.5 months), and most responders required additional treatments. The overall toxicity was minimal and patient compliance was high. This combination is useful for the palliative treatment of small cell lung cancer when aggressive chemotherapy is inappropriate.


The effect of photodynamic therapy on postoperative pain in teeth with primary endodontic infection.
The objective of this study was to investigate the action of photodynamic therapy on pain control after endodontic treatment in asymptomatic teeth with a primary infection, within a single visit. Sixty (60) single-rooted teeth with pulp necrosis and periapical lesions were selected and randomly divided into two (2) groups (n = 30), according to the protocol; a control group (CG) and a group using photodynamic therapy (aPDT). The canals were instrumented with Reciproc files # 25 up to 40 along the entire length of the canal, using 2% chlorhexidine gel as the auxiliary chemical substance, followed by irrigation with sterile saline. aPDT consited of 0.005% methylene blue as photosensitizer, using AsGaAl diode laser, 660 nm wavelength, 100 mW of power and 9 J of energy, using optical fibers with 365 μm in diameter. The canals were filled with Endomethasone N cement. Pain intensity was assessed at 8, 12, 24, 48, 72 h and 1 week after endodontic treatment using a visual analogue scale. The level of pain was classified as none (0), mild (1-3), moderate (4-7) or severe (8-10). The data were at a significance level of 5%. There was a statistically significant difference (p<0.05) in the periods of 8, 12, 24, 48 and 72 h between the control group and the aPDT group. After 1 week, there was no statistically significant difference. It is concluded that photodynamic therapy had a significant effect on decreasing post-endodontic treatment pain in teeth with necrotic pulp and asymptomatic periapical lesions.


A concise synthesis of peramine, a metabolite of endophytic fungi.
The total synthesis of peramine, a natural product isolated from an endophytic fungi, has been achieved in four steps and 34% overall yield from known compounds. The key step was the one-pot construction of the pyrrolopyrazinone ring from pyrrole amide and propargyl bromide. The preparation of peramine-d4 as an internal standard for quantitative analysis by MS is also described.