No mood-altering effects found after treatment of normal subjects with bright light in the morning.
Studies have shown that depressed patients with seasonal affective disorder (SAD) respond to treatment with bright artificial light. In this study 2 hours of bright artificial light administered in the morning for 1 week did not alter mood in 11 normal subjects. This finding suggests that the mood-enhancing effect of light for SAD patients is not necessarily generalizable to other populations.


[Recombinant growth hormone for support of ovarian gonadotropin treatment in a hypophysectomized patient: a case-control study].
In a patient, suffering of apituitarism after the surgical removal of a cranyopharyngeoma at the age of 14, was treated with various doses of human urinary gonadotropin preparations for in vitro fertilization and embryo transfer. The first five treatments were performed without the additional administration of recombinant growth hormone, but due to the administration of increasing doses of exogenous gonadotropins a pregnancy was finally achieved leading to the birth of a healthy girl. Later, as the couple desired a second baby, the treatment was repeated using a low dose of gonadotropins in combination with recombinant growth hormone. This combined treatment was immediately successful, leading to the birth of a healthy boy. The present communication offers a complete survey of the existing literature about the use of recombinant growth hormone in support of ovarian stimulation with gonadotropins. The ongoing controversy is caused by the lack of an established methodology for the diagnosis of growth hormone deficiency. Whereas the efficacy of the additional use of recombinant growth hormone in support of ovarian stimulation with gonadotropins is established in patients without any endogenous growth hormone secretion, its use in patients with less defined hormonal disturbances remains controversial.


Novel Phytochemical Constituents and Anticancer Activities of the Genus, Typhonium.
Typhonium is the largest genus in the Araceae family (~70 species), distributed in South Asia, Southeast Asia and Australia. Typhonium is well-known for its ethnopharmacological uses, and Southeast Asians consider it as an alternative medicine to treat cancer. This review elucidated the confirmed chemical structures of the isolated compounds of Typhonium and emphasized on their anticancer activities against various human cancer cells. Among several species, Typhonium blumei, T. flagelliforme, T. divaricatum and T. giganteum were extensively studied due to the presence of a class of secondary metabolites. All the available reports on Typhonium were included and discussed in this article. Until now several groups of compounds, namely amino acids (1, 2), cinnamic acid (3), fatty acids (4-14), glycerol derivatives (15-18) and cerebrosides (19-34), flavonoids (35), hydantoins (36-38), lignin monomers (39-44), nucleobases (45-48), pheophorbides (49-52), phthalate (53), terpene and steroids (54-59) and vitamins (60, 61) were isolated and characterized from Typhonium. These phytochemicals were investigated for their anticancer properties, and results confirmed the promising growth inhibitory effect and anticancer activities against human lung, breast, prostate and colon cancer cells. The anticancer activity of these compounds appears to be mediated through the induction of apoptotic cell death. These phytochemicals further reported to exhibit other pharmacological efficacies, including anti-inflammatory, antioxidant, antiviral, anti-allergic, neuroprotective and hepato-protective properties. This is the first review to summarize the anticancer properties of all isolated compounds of Typhonium genus with confirmed chemical structures. Further advanced studies are necessary to establish the detailed signaling pathways that are involved in the anticancer property of the compounds.


Cognition and mental health in menopause: A review.
Cognitive and mood changes are frequently mentioned as complaints before, during and after menopausal transition. There is substantial biological evidence for such associations to occur, as there are many mechanisms through which oestrogens can affect the brain: by regulating metabolism, increasing cerebral blood flow and dendritic outgrowth, by acting on nerve growth factors through the co-localisation of receptors via neurotransmitter synthesis and turnover and many more. However, the evidence for objective and longer-term changes in cognitive function and mental health over the menopausal transition and beyond is less clear. While hormone treatment (HT) including oestrogens could potentially reverse these psychological issues, the evidence of long-term benefit is also inconclusive. However, for women with severe menopausal complaints, and particularly for those who undergo early menopause, including women with premature ovarian insufficiency, personalised HT at least up to the natural age of menopause around 50 should be considered, which is probably safe up to 10 years of treatment, unless contraindicated. This paper reviews the evidence for changes in psychological health related to menopausal transition and HTs.


The effect of 4MA, a potent inhibitor of 5 alpha-reductase, on the growth of androgen-responsive human genitourinary tumors grown in athymic nude mice.
The five alpha-reductase inhibitors are a newly developed family of compounds that block the intracellular conversion of testosterone (T) to dihydrotestosterone (DHT). 17-beta-N, N-Diethylcarbamoyl-4-methyl-4-aza-5-alpha-androstan-3-one (4MA), the most widely studied of these compounds, has been shown to inhibit the androgen-dependent growth of both normal animal tissues and of the Noble tumor, an experimental, hormone-responsive rat neoplasm. 4MA has been found to inhibit androgen-dependent growth without altering plasma levels of T or DHT. In the present study, we assessed the efficacy of 4MA in inhibiting the growth of PC-82 and R198, human androgen-responsive genitourinary malignancies. In the first experiment, 4MA was administered subcutaneously at a dose of 6 mg/kg/day to castrated and hormonally replaced groups of PC-82-bearing male athymic nude mice. 4MA therapy when compared to control therapy caused significant PC-82 growth inhibition in three different groups of hormonally replaced castrated mice: physiologic T-replaced (P less than .001), supraphysiologic T replaced (P less than .001), and supraphysiologic T and DHT replaced (P less than .001). There was no difference between the post therapy plasma levels of T or DHT in the control-treated and 4MA-treated mice. In the second experiment, the effect of 4MA (6 mg/kg/day S.Q.) was compared to that of castration and control therapy on the growth of R198. Both castration and 4MA therapy effectively inhibited R198 growth when compared to control therapy (P = .01 and .02, respectively), but there was no difference in the degree of growth inhibition seen with 4MA or castration (P = .45). Castration and 4MA-therapy significantly lowered plasma T levels when compared to control therapy; castration also significantly lowered plasma DHT levels, while 4MA and control therapy did not. These studies suggest that 4MA is effective in inhibiting the growth of human androgen-responsive tumors grown in athymic nude mice and that further studies with other 5 alpha-reductase inhibitors are indicated.


Fabrication of multifunctional materials based on chitosan/gelatin incorporating curcumin-clove oil emulsion for meat freshness monitoring and shelf-life extension.
A new multifunctional film with active and intelligent effects was developed by incorporating curcumin-clove oil emulsion into natural materials. The basic properties, functional characteristics, and pH/NH3-sensitivity of films were investigated, and then these films were applied to extend shelf-life and monitor freshness of meat. Curcumin solution and emulsion illustrated significant color variations at different pH values. The incorporation of emulsion improved the UV-vis barrier and water resistance properties of films, which blocked most of UV-light and its water contact angle reached 100.03°. Meanwhile, the films had stronger mechanical strength and higher thermal stability, with elongation at break reaching 79.18 % and the maximum degradation temperature rising to 316 °C. Moreover, emulsion made films have a slow-release effect on clove oil, which not only enhanced the antioxidant property but also significantly improved their antibacterial activity. Additionally, the multifunctional films presented a significant color response to acidic/alkaline environments over a short time interval and could be easily identified by naked eyes. Finally, the films effectively extended the shelf-life of fresh meat by 3 days at 4 °C and visually monitored freshness through color changes in real-time. This knowledge provides insights and ideas for the development of novel food packaging with both active and intelligent functions.


A longitudinal functional magnetic resonance imaging study of language development in children 5 to 11 years old.
Language skills continue to develop rapidly in children during the school-age years, and the "snapshot" view of the neural substrates of language provided by current neuroimaging studies cannot capture the dynamic changes associated with brain development. The aim of this study was to conduct a 5-year longitudinal investigation of language development using functional magnetic resonance imaging in healthy children. Thirty subjects enrolled at ages 5, 6, or 7 were examined annually for 5 years using a 3-Tesla magnetic resonance imaging scanner and a verb generation task. Data analysis was conducted based on a general linear model that was modified to investigate developmental changes whereas minimizing the potential for missing data. With increasing age, there is progressive participation in language processing by the inferior/middle frontal, middle temporal, and angular gyri of the left hemisphere and the lingual and inferior temporal gyri of the right hemisphere and regression of participation of the left posterior insula/extrastriate cortex, left superior frontal and right anterior cingulate gyri, and left thalamus. The age-related changes observed in this study provide evidence of increased neuroplasticity of language in this age group and may have implications for further investigations of normal and aberrant language development.


Regulation of TXB(2) and PGE(2) production by TGF-beta(1) in in vitro silica dust-exposed rat alveolar macrophage.
We investigated the effect of transforming factor factor-beta(1) (TGF-beta(1)) on thromboxane B(2) (TXB(2)) and prostaglandin E(2) (PGE(2)) production in in vitro silica dust-exposed rat alveolar macrophages (AM). In the presence of 5 mug of anti-TGF-beta(1) antibodies, TXB(2) production decreased, but PGE(2) production increased. Addition of 2 ng of TGF-beta(1) to the culture medium potentiated TXB(2) production, but PGE(2) production apparently did not change. At 50 ng of TGF-beta(1), TXB(2) production decreased, and PGE(2) production varied. Our data suggest that in rat AM: (1) both endogenous and exogenous TGF-beta(1) regulate TXB(2) production; and (2) in the absence of endogenous TGF-beta(1) the liberation of PGE(2) increases; however, exogenous TGF-beta(1) does not have a regulatory effect on PGE(2).


Chromosome distribution studies after inorganic lead exposure.
We studied the chromosome distribution in persons professionally exposed to inorganic lead. The degree of lead exposure was evaluated by biochemical measurements and cytogenetic analysis. The chromosome distribution was analyzed from trypsin banded karyotypes; in particular we studied centromere distances (delta2) and centromere-metaphase-center distances (d2) which were obtained by computer-aided mathematical transformation of the individual metaphase coordinates. Higher concentrations of blood lead and urine delta-ALA and a statistically significant increase in aneuploidy, hypoploidy, and type-B chromosome aberrations revealed appreciable exposure although none of the subjects showed signs of excessive lead absorption. However study of the chromosome distribution showed no major differences with that of the controls indicating that lead acts preferentially (directly or indirectly) on the chromosomes rather than on the spindle apparatus. A dissociation of the acrocentric chromosomes was observed in the lead group when compared with the controls. This is thought to reflect a secondary action of lead on the nucleolar organiser regions.


The comprehensive complication index (CCI): proposal of a new reporting standard for complications in major urological surgery.
The comprehensive complication index (CCI) is a new tool for reporting the cumulative burden of postoperative complications on a continuous scale. This study validates the CCI for urological surgery and its benefits over the Clavien-Dindo-Classification (Clavien). Data from a prospectively maintained data base of all consecutive patients at a university care-center was analyzed. Complications after radical cystectomy (RC), radical prostatectomy (RP), and partial nephrectomy (PN) were classified using the CCI and Clavien system. Differences in complications between the CCI and the Clavien were assessed and correlation analyses performed. Sample size calculations for hypothetical clinical trials were compared between CCI and Clavien to evaluate whether the CCI would reduce the number of required patients in a clinical trial. 682 patients (172 RC, 297 RP, 213 PN) were analyzed. Overall, 9.4-46.6% of patients had > 1 complication cumulatively assessed with the CCI resulting in an upgrading in the Clavien classification for 2.4-32.4% of patients. Therefore, scores between the systems differed for RC: CCI (mean ± standard deviation) 26.3 ± 20.8 vs. Clavien 20.4 ± 16.7, p < 0.001; PN: CCI 8.4 ± 14.7 vs. Clavien 7.0 ± 11.8, p < 0.001 and RP: CCI 5.8 ± 11.7 vs. Clavien 5.3 ± 10.6, p = 0.102. The CCI was more accurate in predicting LOS after RC than Clavien (p < 0.001). Sample size calculations based in the CCI (for future hypothetical trials) resulted in a reduction of required patients for all procedures (- 25% RC, - 74% PN, - 80% RP). The CCI is more accurate to assess surgical complications and reduces required sample sizes that will facilitate the conduction of clinical trials.


Weight catch-up and achieved schooling at 18 years of age in Brazilian males.
To assess the relationship between weight catch-up in infancy and achieved schooling at 18 years of age in Brazilian males. All newborn infants in the city's hospitals were enrolled in 1982; 78.8% (2250) of all male participants were located at age 18 years when enrolling in the national army. According to the Brazilian school calendar, 18-year-olds should be attending the 11th grade, but school failure was very common and 78.5% of all subjects had failed at least once. The average achieved schooling was 7.7 years (s.d.=2.3). After controlling for possible confounding variables, birthweight was positively associated with achieved schooling. With respect to postnatal growth, weight gain in the first 20 months was associated with increased schooling. Among SGA infants who caught-up in weight, achieved schooling was 1.3 higher. Data from a cross-sectional survey in the same population suggest that such a difference corresponds to a 25% difference in adult income levels. The study showed that early weight catch-up is associated with achieved schooling. The beneficial effects of early weight gain should be balanced against its potential harms.


Chitinases and chitinase-like proteins in T(H)2 inflammation and asthma.
Chitin is the second most abundant biopolymer in nature, where it protects crustaceans, parasites, fungi, and other pathogens from the adverse effects of their environments, hosts, or both. Because chitin does not exist in mammals, it had been assumed that the chitinases that degrade it are also restricted to lower life forms. However, chitinases and chitinase-like proteins have recently been noted in mice and human subjects. The prototypic chitinase, acidic mammalian chitinase, was also noted to be induced during T(H)2 inflammation through an IL-13-dependent mechanism. It was also shown to play an important role in the pathogenesis of T(H)2 inflammation and IL-13 effector pathway activation and demonstrated to be expressed in an exaggerated fashion in human asthmatic tissues. The finding that chitinases contribute to host anti-parasite responses and asthmatic T(H)2 inflammation support the concept that asthma might be a parasite-independent anti-parasite response.


Predominance of trisomy 1q in myelodysplastic syndromes in Korea: is there an ethnic difference? A 3-year multi-center study.
A predominance of total or partial chromosomal losses and the rarity of translocations are characteristics of myelodysplastic syndrome (MDS), and 5q,-5, -7 and +8 are known to be the most predominant chromosomal changes. To investigate whether the incidence and the pattern of chromosomal changes in MDS varies by location in Korea, we reviewed the cytogenetic results of 205 MDS cases from three medical centers. Distribution of MDS subtypes and the incidence of chromosomal aberration (44.8%) of MDS in Korea were similar to those found in other countries, however, their patterns were different. Translocations (40.4%) predominated over partial or total deletions (36.3%) in Korea. The most common abnormalities in MDS were trisomy 8, trisomy 1q, -5/5q-, and -7/7q-, which occurred in 18(19.5%), 14(15.2%), 12(13.0%), and 11(11.9%) patients, respectively. It is of note that trisomy 1q, which is rarely reported in hematologic malignancies, was the second most common change associated with MDS in Korea, and that structural anomalies of chromosomes 1(19.6%) exceeded that of chromosome 5(15.2%). The most common sole anomalies were trisomy 8(7.6%) and 14(78%) of 18 cases with chromosome 1 anomalies accompanied by other chromosomal abnormalities, suggesting that the changes of chromosome 1 may be evolutionary events rather than sporadic events. In conclusion, trisomy 1q and trisomy 8 predominate in Korean MDS, suggesting the likelihood of ethnic differences.


Allergic contact dermatitis from a natural deodorant: a report of 4 cases associated with lichen acid mix allergy.
Botanical ingredients used in personal care products are a significant and underreported cause of allergic contact dermatitis. To evaluate allergic contact dermatitis from a widely-used botanical deodorant. We conducted patch testing in four patients who were using the botanical deodorant and were referred to the contact dermatitis clinic; three patients had axillary dermatitis and one had dermatitis of the external ear. All four patients had positive patch test reactions to lichen acid mix and D-usnic acid. Of the three patients who were patch tested to the botanical deodorant, all had positive reactions. We did not test to the specific lichen used in the natural deodorant but rather used our own lichen acid mix and d-usnic acid in addition to testing to the actual product. One of the patients declined to be tested with the natural deodorant, but did test positive to the lichen acid mix and d-usnic acid. Personal care products such as deodorants may represent a new route of exposure to lichen extract, a known allergen.


Primary maternal cytomegalovirus infections: accuracy of fetal ultrasound for predicting sequelae in offspring.
Cytomegalovirus infection is the most common perinatal viral infection that can lead to severe long-term medical conditions. Antenatal identification of maternal cytomegalovirus infections with proven fetal transmission and potential postnatal clinical sequelae remains a major challenge in perinatology. There is a need to improve the prenatal counseling offered to patients and guide future clinical management decisions in cases of proven primary cytomegalovirus infection. We sought to evaluate the accuracy of fetal ultrasound for predicting sequelae in fetuses infected with congenital cytomegalovirus after maternal primary infection. We conducted a prospective observational study from 1996 through 2012 in pregnant women with serological evidence of primary cytomegalovirus infection and proven vertical transmission to the fetus, based on viral load in the amniotic fluid. Fetal ultrasound was performed in all patients. Pregnancy termination was presented as an option for infected fetuses. Hearing and neurological clinical assessments were performed for all neonates with cytomegalovirus-positive urine samples. A total of 67 patients (69 fetuses) with proven vertical transmission were included in this study, including 64 singleton and 3 twin pregnancies. Eight fetuses were lost to follow-up. Of the remaining 61 fetuses, termination of the pregnancy was performed for 26, including 11 with fetal ultrasound anomalies. Autopsy provided histological evidence of fetal cytomegalovirus infection in all cases. In the 15 terminated fetuses without ultrasound anomalies, histological evidence of damage caused by fetal infection was detected in 13 cases. Among the 35 live-born infants, 12 had fetal ultrasound anomalies suggestive of congenital infection. Of these 12 infants, 6 had normal clinical evaluations, whereas 6 presented with either hearing and/or neurological anomalies, classified as severe in 4 cases. Among the 23 live-born infants with normal prenatal ultrasound, 5 developed hearing impairments and 1 showed mild neurological developmental delay. Fetal ultrasound anomalies were detected in 37.7% of pregnant women with primary cytomegalovirus infection acquired in early pregnancy and proven fetal infection, and were confirmed by autopsy or postnatal clinical evaluation in 73.9%. Autopsy or postnatal clinical evaluation also detected cytomegalovirus-related anomalies in 55% of infants with normal fetal ultrasound evaluations.


Narrow-band filtering for monitoring low-amplitude cone electroretinograms in retinitis pigmentosa.
Low amplitude (less than 10 microV) cone electroretinograms, elicited with 30-Hz white flicker from 59 patients with retinitis pigmentosa, were computer-averaged alone or in combination with a narrow-band electronic filter that increases the signal to noise ratio, thereby making it possible to evaluate the electroretinograms of most patients with retinitis pigmentosa. Narrow-band filtering reduced the amplitude of computer-averaged responses by an average of 7%, but the change in amplitude was independent of the size of the unbandpassed response. Narrow-band filtering also allowed measurement of 30-Hz cone responses in patients followed up over an 11- to 15-year period and quantitation of responses of less than 1 microV, which were not detectable with computer averaging alone.


Endemic High-Risk Clone ST277 Is Related to the Spread of SPM-1-Producing Pseudomonas aeruginosa during the COVID-19 Pandemic Period in Northern Brazil.
Pseudomonas aeruginosa is a high-priority bacterial agent that causes healthcare-acquired infections (HAIs), which often leads to serious infections and poor prognosis in vulnerable patients. Its increasing resistance to antimicrobials, associated with SPM production, is a case of public health concern. Therefore, this study aims to determine the antimicrobial resistance, virulence, and genotyping features of P. aeruginosa strains producing SPM-1 in the Northern region of Brazil. To determine the presence of virulence and resistance genes, the PCR technique was used. For the susceptibility profile of antimicrobials, the Kirby-Bauer disk diffusion method was performed on Mueller-Hinton agar. The MLST technique was used to define the ST of the isolates. The exoS+/exoU- virulotype was standard for all strains, with the aprA, lasA, toxA, exoS, exoT, and exoY genes as the most prevalent. All the isolates showed an MDR or XDR profile against the six classes of antimicrobials tested. HRC ST277 played a major role in spreading the SPM-1-producing P. aeruginosa strains.


Reference distributions for immunoglobulins A, G, and M: a practical, simple, and clinically relevant approach in a large cohort.
Serum immunoglobulins are measured millions of times each year, yet clinical interpretations remain hampered by inadequate age- and gender-specific reference limits. In order to provide more reliable and comprehensive reference distributions for IgA, IgG, and IgM measurements, we analyzed automated immunoassay values from 115,017 serum samples from northern New England patients (99% Caucasian) who were tested in our laboratory between 1986 and 1995. Measurements were standardized to reference material, CRM 470 (RPPHS). A simple, practical, and clinically relevant approach was used to determine reference distributions for the immunoglobulins over a wide range of ages for males and females. Levels of IgA and IgM varied considerably by age, and by gender for IgM. For each of the analytes, the observed 5th and 95th centiles were symmetric about the median and approximately constant over the entire age range. When immunoglobulin reference values are expressed as multiples of the age- and gender-specific regressed medians, the resulting distributions fit a log-Gaussian distribution well. This finding enables interpretation of serum immunoglobulin measurements using a common unit (multiples of the median) that is independent of age or gender. Insights gained from this study can help improve and simplify the interpretation of immunoglobulin measurements.


The Glu318Gly mutation of the presenilin-1 gene does not necessarily cause Alzheimer's disease.
In early-onset familial Alzheimer's disease (AD) pathogenic mutations have been found in the amyloid precursor protein (APP) gene and in the presenilin (PS)-1 and PS-2 genes. We screened for mutations in these genes in 20 patients with familial AD from the Finnish population. In addition, we sampled 41 sporadic AD patients and 59 controls to test for mutations identified in our familial AD cases. We detected an A-to-G transition in the PS-1 gene, resulting in a glutamic acid (Glu)-to-glycine (Gly) substitution at codon 318 in 2 familial and 2 sporadic AD patients. The Glu318Gly mutation has previously been reported to cause AD. We also found the Glu318Gly mutation in 4 healthy aged controls (range, 74-87 years). We thus conclude that the mutation is most likely a rare polymorphism not related to AD.


Identification of the Relationship Between DNA Methylation of Circadian Rhythm Genes and Obesity.
In children, teenagers, and young adults, environmental factors and genetic modifications have contributed to the development of obesity. There is a close relationship between obesity and circadian rhythm. To understand the role of CLOCK and BMAL1 in obesity, we analyzed the methylation status of CLOCK and BMAL1 in obese and control subjects. In this paper, we analyzed the methylation status of the CLOCK and BMAL1 genes by using MS-HRM in a total of 55 obese and 54 control subjects. In our study, we demonstrated that the level of fasting glucose and the level of HDL-cholesterol were associated with CLOCK methylation in obesity. We also showed a significant association between BMAL1 gene methylation and waist and hip circumference in obese subjects. This is the first study that shows the methylation of BMAL1 is associated with the obese phenotype. However, we could not show a direct association between CLOCK methylation and the obese phenotype. In this paper, a novel epigenetic interaction between circadian clock genes and obesity was demonstrated.


Staging of gastroenteropancreatic neuroendocrine tumors: how we do it based on an evidence-based approach.
In contrast to other common types of malignant tumors, the vast majority of gastroenteropancreatic neuroendocrine tumors are well differentiated and slowly growing with only a minority showing aggressive behavior. It is important to accurately stage patients radiologically so the correct treatment can be implemented and to improve prognosis. In this article, we critically appraise the current literature in an effort to establish the current role of radiologic imaging in the staging of neuroendocrine tumors. We also discuss our protocol for staging neuroendocrine tumors.


Management of post appendicectomy intra-abdominal collections: A volumetric cut off for drainage?
Intra-abdominal collections (IAC) are a common complication following appendicectomy, one of the most commonly performed emergency abdominal procedures in childhood. The option to drain a collection is frequently available but not always required. The aim of this study was to compare the outcomes of medically and procedurally-managed post appendicectomy IACs and suggest a method of standardising the need for intervention. A single centre, retrospective review of children aged ≤ 16 years presenting between 2014 and 2019 was performed. Patient demographics, management, and outcome data were collected. IAC volume and surface area were calculated assuming a prolate spheroid or true ellipsoid depending on the number of dimensions reported. 60 patients (18%) of 334 patients developed an IAC post appendicectomy. Medical management was undertaken in 44 (73%), drainage in 12 (20%), and surgical washout in 4 (7%). Collection size was associated with failure of medical management: maximum diameter (p = 0.028), volume (p = 0.002), and surface area (p = 0.001). Collections with a volume of 2 ml/kg were significantly less likely to fail medical management than larger collections (0/33 vs 6/11; p < 0.0001). Not all post appendicectomy IACs require drainage. The relationship between collection volume and need for drainage is more closely assessed using a volume calculation rather than a single dimension measurement, particularly when adjusted for weight of the child. A cut off of 2 ml/kg appears to be a good objective measure for intervention and provides a communication tool for discussion amongst the multidisciplinary team. Prospectively collected multicentre data on this subject would be timely. III.


Preparation of scaffolds from human hair proteins for tissue-engineering applications.
Human hair proteins were isolated and purified for the fabrication of tissue-engineering scaffolds. Their cellular compatibility was studied using NIH3T3 mice fibroblast cells. The proteins were characterized using FTIR spectroscopy, sodium dodecyl sulfate-polyacrylamide gel electrophoresis for molecular weights and two-dimensional polyacrylamide gel electrophoresis for their isoelectric points (pIs). The molecular weights of keratins were in the range of 40-60 kilo-Daltons (kDa) and of matrix proteins were in the range of 15-30 kDa. The pIs of keratins were found to be in the range of 4.5-5.3. Sponges of the proteins were formed by lyophilization. Scanning electron microscopy was performed to examine the surface. Swelling studies were carried out in phosphate buffer saline at physiological pH 7.4. The hydrophilic character of the protein surface was studied by determining an average contact angle, which came to be 37 degrees. The wells of tissue culture plates were coated with these proteins for studying the attachment and morphology of the cells. The protein detachment study was done to ensure the adsorption of proteins on the wells until the completion of the experiments. The cellular growth on a protein-coated surface showed three-dimensional 'bulged' morphology due to cell-cell and cell-matrix contacts. The sponges of human hair proteins supported more cells for a longer period than control. The morphology and cell proliferation studies exhibited by NIH3T3 cells on these proteins have shown their potential to be used as tissue-engineering scaffolds with better cell-cell contacts and leucine-aspartic acid-valine (LDV)-mediated cell-matrix interactions.


Cell Factory Design and Optimization for the Stereoselective Synthesis of Polyhydroxylated Compounds.
A synthetic cascade for the transformation of primary alcohols into polyhydroxylated compounds in Escherichia coli, through the in situ preparation of cytotoxic aldehyde intermediates and subsequent aldolase-mediated C-C bond formation, has been investigated. An enzymatic toolbox consisting of alcohol dehydrogenase AlkJ from Pseudomonas putida and the dihydroxyacetone-/hydroxyacetone-accepting aldolase variant Fsa1-A129S was applied. Pathway optimization was performed at the genetic and process levels. Three different arrangements of the alkJ and fsa1-A129S genes in operon, monocistronic, and pseudo-operon configuration were tested. The last of these proved to be most beneficial with regard to bacterial growth and protein expression levels. The optimized whole-cell catalyst, combined with a refined solid-phase extraction downstream purification protocol, provides diastereomerically pure carbohydrate derivatives that can be isolated in up to 91 % yield over two reaction steps.


Increased risk of pyogenic liver abscess in patients with alcohol intoxication: A population-based retrospective cohort study.
We designed a population-based retrospective cohort study to investigate the association between the event of alcohol intoxication and the risk of pyogenic liver abscess. The present study enrolled 245,076 patients with a history of alcohol intoxication from 2000 to 2010 and matched each of them with four comparison patients, with similar mean age and sex ratios. We determined the cumulative incidences and adjusted hazard ratios (aHRs) of liver abscess. A significant association was observed between alcohol intoxication and liver abscess. The incidence density rate of liver abscess was 3.47-fold greater in the alcohol intoxication (AI) cohort than in the non-AI cohort (12.2 vs. 3.43 per 10,000 person-years), with an adjusted HR (aHR) of 2.64 (95% CI = 2.26 to 3.08). This population-based study positively associated the event of alcohol intoxication with increased risk of liver abscess. Our findings warrant further large-scale and in-depth investigations in this area.


Poly(methyl methacrylate)s with pendant calixpyrroles: polymeric extractants for halide anion salts.
Poly(methyl methacrylate)s containing pendant octamethylcalix[4]pyrrole subunits were prepared and demonstrated to be capable of extracting tetrabutylammonium chloride and fluoride salts from aqueous media.


Influenza A virus reassortants with surface glycoprotein genes of the avian parent viruses: effects of HA and NA gene combinations on virus aggregation.
A series of 33 human-avian and human-mammalian influenza virus reassortant clones possessing either HA or both HA and NA genes of the avian or mammalian virus was obtained by crosses of A/USSR/90/77 (H1N1) human virus with 5 avian and 1 mammalian influenza virus strains. All of the reassortants possessing NA genes of the H1N1 human parent virus and HA gene of an avian or mammalian parent virus had high values of infectivity/HA activity ratio. Since this feature could result from a limited virion aggregation, several reassortants were analyzed by velocity sucrose gradient centrifugation. In all cases tested, the reassortants of H3N1, H4N1, H10N1 and H13N1 composition were shown to be aggregated, whereas the preparations of the parent H1N1 virus and the reassortants possessing both HA and NA genes from the avian parents were represented mostly by single virions. The aggregates were formed at 4 degrees C and dissociated at 37 degrees C. The dissociation was blocked by an inhibitor of neuraminidase activity (2-deoxy-2,3-dehydro-N-acetyl-neuraminic acid). The dissociation was reversible since the virions reaggregated at 4 degrees C; however, treatment with bacterial neuraminidase led to an irreversible dissociation of the aggregates. The tendency of the reassortants to aggregate correlates with an increased infectivity/HA ratio. No regular decrease in the neuraminidase activity in the virions of reassortants as compared to the parent H1N1 virus was revealed. The most likely explanation of the observed phenomenon seems to be an inefficient removal of sialic acid residues from the avian virus hemagglutinin by the human virus N1 neuraminidase.


Therapeutic role of granulocyte colony-stimulating factor (G-CSF) for infertile women under in vitro fertilization and embryo transfer (IVF-ET) treatment: a meta-analysis.
The aim of this meta-analysis is to explore the beneficial role of granulocyte colony-stimulating factor (G-CSF) on infertile women under artificial reproduction technology treatment. Medline, Embase and ISI Web of Science databases were searched to identify relevant randomized control trials. Studies before July, 2017 were included for primary screening. Meta-analysis of the total and subgroup patients was conducted, and relative risks (RRs) and their 95% confidence intervals (95% CI) were calculated by a fixed-effect model if no heterogeneity (evaluated as I2 statistic) existed. Otherwise, a random-effects model was adopted. Subgroup analysis was performed by administrating route or clinical indication. Egger test and influence analysis were conducted to evaluate the publication bias and study power, respectively. The final selection enrolled 10 RCTs, involving 1016 IVF-ET cycles (521 distributed to the G-CSF group and 495 to the control). Compared with control group, G-CSF administration could significantly improve clinical pregnancy rate (CPR, RR 1.89, 95% CI 1.53-2.33), while it had no beneficial effect on embryo implantation rate (IR, RR 1.84, 95% CI 0.84-4.03). The subgroup analysis by administration route showed that both uterine infusion and subcutaneous injection can produce a substantial increase in CPR, with the pooled RRs (95% CI) 1.46 (1.04-2.05) and 2.23 (1.68-2.95), respectively. Nevertheless, most of included RCTs dealt with the RIF subjects, and the pooled analysis of this data showed a higher PR and IR in G-CSF group as compared to that in the control, with the RRs (95% CI) 2.07 (1.64-2.61) and 1.52 (1.08-2.14), respectively. Egger regression test did not demonstrate any significance for the publication bias. G-CSF administration has a beneficial role on the clinical outcome after embryo transfer by both routes of local infusion and systematic administration, especially for the cases with RIF. Further RCTs are needed to investigate the role of G-CSF in thin endometrium patients.


[EFFECTS OF LEUCOCYTE- AND PLATELET-RICH PLASMA ON OSTEOGENIC DIFFERENTIATION OF BONE MARROW MESENCHYMAL STEM CELLS IN TREATING AVASCULAR NECROSIS OF FEMORAL HEAD IN RABBITS].
To evaluate the effect of leucocyte- and platelet-rich plasma (L-PRP) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in treating avascular necrosis of the femoral head (ANFH) in rabbits. Twenty-four New Zealand white rabbits (4-6 months old, both genders, weighing 2.0-3.0 kg) were used for the establishment of bilateral ANFH models and divided into 4 groups (n = 6). BMSCs were isolated from the bone marrow of iliac crest, cultured and identified. L-PRP was prepared by Landesberg method. Core decompression only (group A), core decompression and L-PRP implantation (group B), core decompression and BMSCs implantation (group C), and core decompression and implantation of BMSCs and L-PRP were performed in 4 groups. To evaluate bone formation and remodeling of the defects, X-ray photography was taken at 2, 4, and 8 weeks postoperatively. The modified Lane-Sandhu scoring system was used to evaluate the bone formation. Two rabbits were sacrificed at 2, 4, 8 weeks after operation to harvest the specimens for histological observation, new blood vessel count and new bone area ratio. The observations of radiology and histology displayed different degrees of bone regeneration at bone defect sites in each group. At 2, 4, and 8 weeks postoperatively, the results of Lane-Sandhu X-ray photography scoring, new blood vessel count, and new bone area ratio showed that groups C and D were significantly better than groups A and B, group D was significantly better than group C. and group B was significantly better than group A (P < 0.05). These findings demonstrate that L-PRP can promote osteogenic differentiation of BMSCs in treating ANFH in rabbits, and core decompression associated with BMSCs and L-PRP is an effective and feasible method to treat ANFH.


Cytolytic activity of macrophages isolated from primary murine sarcoma virus (MSV)-induced tumors.
Macrophages isolated from regressing or progressing tumors induced by murine sarcoma virus (MSV) were tested for cytolytic activity in a 18-h 51Cr release assay. Macrophages from the tumors of mice injected 14 days earlier with stocks of MSV-producing regressor or progressor tumors had comparable levels of cytotoxicity. However, macrophages from the progressively growing tumors, 50--65 days after the inoculation with the progressor virus, had lower levels of cytotoxicity than those from the regressing tumors (day 14). On the other hand, macrophages from progressively growing MSV tumors (day 14) in nude mice had little or no detectable cytolytic activity. In a fractionation study, using the 1-g velocity sedimentation technique, cells from regressing tumors (day 14) showed at least two peaks of cytolytic activity, one at about 4 mm/h and another at 6--7 mm/h. In contrast, none of the cell fractions of tumors from nude mice (day 14) showed cytolytic activity. Since bacterial lipopolysaccharide (LPS) has been shown to augment the cytolytic activity of primed macrophages, its effect on cells from MSV tumors was evaluated. Cytolytic activity of the cells from regressing or progr-ssing tumors that had pre-existing cytolytic activity was augmented by the addition of LPS during the assay period, but LPS treatment did not activate inactive fractions or change the distribution patterns of the cytolytic activity in fractions from 1-g velocity sedimentation.


Quantification and characterization of insoluble chitinous materials in viscous chitosan solutions.
Insoluble chitinous materials in highly viscous chitosan solutions can be quantified using the viscosity-lowering action of transglucosidase (EC 184.108.40.206). In chitosan, commonly produced by high temperature deacetylation (90 degrees C), between 70-90% of insoluble chitinous materials were recovered by this enzymatic method whereas only 25% recovery was obtained by the nitrous acid method. The insoluble material recovered after enzyme treatment had a higher degree of deacetylation and a lower degree of crystallization than that after nitrous acid treatment. The results are explained by difference in penetration by enzyme and nitrous acid into the insoluble particle.


[The treatment of sternal wound infection by internal fixation of sternum with titanium plate after cardiac surgery].
To investigate the internal fixation of sternum with titanium plate for the treatment of sternal wound infection after cardiac surgery. A retrospective study of 26 patients from Jan 2009 to Dec 2011 was carried out. All the 26 cases with sternal wounds infection after cardiac surgery, were treated by internal fixation with titanium plates. All the patients had chronic infection, lasting for more than 3 months. 3 patients received vacuum-assisted closure treatment after complete debridement. All the wounds were covered with pectoral major muscle flap. All the wounds healed completely with no recurrence of infection. Internal fixation of sternum with titanium plate can increase the stability. It helps to improve the treatment efficacy of sternal wound infection after cardiac surgery.


Ovarian cancer patients and hormone replacement therapy: a systematic review.
Although the majority of patients with ovarian cancer are menopausal, approximately one-third are premenopausal at the time of diagnosis. Little information is available concerning the impact of hormone replacement therapy (HRT) on the clinical outcomes of patients previously treated for ovarian cancer. The objective of this review is to determine whether there is any adverse impact on survival among women with ovarian cancer on HRT. A protocol was developed in advance of commencement of this systematic review. It detailed the plan for the search strategy, selection criteria for studies, and methods for data collection and analysis. No limitation of study design was made, and the details of the search strategy are described in the text of the review. Two reviewers independently evaluated the eligibility of all studies and abstracted the data. One randomized trial and two observational studies are included. Due to methodological heterogeneity of the included studies, results have not been pooled in a meta-analysis. The randomized trial presented differences between the intervention and control groups on median overall survival (44 months vs. 34 months/HRT vs. No-HRT) and disease-free survival (34 months vs. 27 months/HRT vs. No-HRT) that were not significant. Similarly, there were nonsignificant differences in survival and recurrence rates in the two included cohort studies. This is a comprehensive systematic review of the evidence concerning HRT in ovarian cancer patients. Until more evidence becomes available, it appears that HRT is acceptable for patients with ovarian cancer as part of supportive and symptomatic therapy.


Investigation of the valence electronic states of Ti(IV) in Ti silicalite-1 coupling X-ray emission spectroscopy and density functional calculations.
We present an application of valence to core X-ray emission spectroscopy to understand the electronic structure of the industrially relevant catalyst titanium silicalite-1. The experimental spectrum was modelled within density functional theory, adopting a one electron approach, investigating the effects of different basis sets, density functionals and cluster sizes. The description of titanium silicalite-1 valence states follows the Kohn-Sham evaluation of the molecular orbitals involved in the computed transitions.


Paneth cell-rich papillary adenocarcinoma and a mucoid adenocarcinoma occurring synchronously in colon: a light and electron microscopic study.
A 71-year-old man who presented with iron deficiency anaemia and weight loss was found to have two colonic tumours: a mucoid adenocarcinoma at the splenic flexure and a papillary adenocarcinoma rich in Paneth cells in the ascending colon. The light and ultrastructural features of the neoplastic cells are described, and the significant of the presence of neoplastic Paneth cells is discussed.


Neuroanesthesia.
Children requiring surgical treatment of epilepsy present many perioperative challenges. They demand the skills of a pediatric neuroanesthesiologist who is familiar with the physiologic and psychological needs of the pediatric patient, in addition to understanding the effects of anesthetic agents on the central nervous system. Not only is it important for the anesthesiologist to be aware of the neurosurgeon's specific operative plans, but also it is essential that the neurosurgeon understand the issues facing the anesthesiologist to avoid preventable intraoperative problems and to facilitate an optimal outcome for the patient.


The thermographic characteristics of varicocele: an analysis of 65 positive registrations.
Sixty-five positive thermograms in patients suspected of subclinical varicocele or presenting with clinically palpable varicocele have been analysed. Two distinct patterns of varicocele associated thermograms could be distinguished, herperthermia always exceeding 1 degrees C. A correlation was found between the clinical grade of varicocele and both the extension and the degree of hyperthermia.


Prognostic Impact of Total Lesion Glycolysis (TLG) from Preoperative 18F-FDG PET/CT in Stage II/III Colorectal Adenocarcinoma: Extending the Value of PET/CT for Resectable Disease.
We investigated the prognostic role of metabolic parameters from preoperative 18F-FDG PET/CT in stage II/III colorectal adenocarcinoma. A total of 327 stage II/III colorectal adenocarcinoma patients who underwent curative resection were included. The maximal standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were analyzed for optimal cut-offs and their effect on DFS. Differences in DFS rates and hazard ratios for DFS between cut-offs were statistically significant in SUVmax, MTV2.5, MTV3, TLG 2.5, TLG3, and TLG30%. Factors significantly related to DFS in univariate Cox regression were age, sex, stage, preoperative CEA, SUVmax, MTV2.5, MTV3, TLG2.5, TLG3, and TLG30%. Age, sex, preoperative CEA, and TLG2.5 (p = 0.009) sustained statistically significant difference in multivariate analysis. The 1-, 3-, and 5-year DFS rates for TLG2.5 ≤ 448.5 were 98.1%, 79.6%, and 74.8%, significantly higher than 78.4%, 68.5%, and 61.1% of TLG2.5 > 448.5, respectively (p = 0.012). TLG, a parameter indicating both the metabolic activity and metabolic volume, was the strongest predictor independently associated with DFS, among several PET parameters with statistical significance. These results suggest the potential prognostic value of preoperative 18F-FDG PET/CT in stage II/III resectable colorectal cancer.


From the archives of MD Anderson Cancer Center: Sporadic Burkitt lymphoma with a complex karyotype and SOX11 expression.
Burkitt lymphoma (BL) is a mature B-cell neoplasm arising from germinal center B-cells. There are three epidemiological variants of which the sporadic variant is most prevalent in developed countries representing 1-2 % of all lymphomas in adults. Patients usually present with bulky abdominal masses and ~ 30 % have bone marrow involvement. BL is characterized by a germinal center B-cell immunophenotype and usually has a simple karyotype. Here we report an unusual case of sporadic BL in a 44-year-old man and we use this case to review sporadic BL in adults. The patient presented with a cecal mass and bone marrow involvement. Biopsy of the cecal mass and bone marrow evaluation showed infiltration by intermediate-size lymphoma cells positive for monotypic kappa, CD10, CD19, CD20, CD22, CD38 bright, CD43, CD45, Bcl6 and ROR1, and negative for CD11c, CD23, CD30, CD44, CD200 and Bcl2. As expected, the lymphoma cells were strongly positive for MYC and Ki-67 showed a proliferation rate of nearly 100 %, but the cells were also positive for SOX11 and cytoplasmic LEF1. Conventional chromosomal analysis revealed t(8;14) as part of a complex karyotype. Based on our literature review, and is shown in this case, sporadic BL in adults shows some differences with the classic description of BL in children. We also discuss the differential diagnosis of BL.


Assessment of natural ventilation strategy to decrease the risk of COVID 19 infection at a rural elementary school.
Natural ventilation in low-budget elementary schools is the main focus to ensure the health and comfort of its occupants, specifically when looking at the global pandemic related to SARS-COV-2. This paper presents an experimental and novel study of natural ventilation in a public elementary school (Los Zumacales), with a particularly low economic budget. The study was carried out during the winter months of the Covid 19 pandemic. The school is located in the rural area of Castilla y León (North-Western Spain) far from high traffic roads. In this study, a methodology of measuring CO2 concentration was applied in nine classrooms in a school. The experimental study shows the level of natural ventilation in each classroom, expressed in Air Changes per Hour (ACH), using the Decay CO2 concentration method. The method is proven by comparing the experimental values of the obtained ACH with those determined by the most powerful methods to achieve appropriate ventilation levels. Thus, ensuring health protection protocol in rural schools, against the COVID 19 pandemic. Harvard guide and Spanish regulations (RITE), two widely recognized methods have been used together with the experimentally obtained standard by Rey et al. Only one classroom showed a value lower than 3 indicating poor ventilation. In this study, the degree of thermal comfort in the nine classrooms were also analyzed according to the EN15251 standard. An average indoor temperature of approximately 19 °C was obtained, and the relative humidity was stable and correct according to Spanish regulations. In addition, the risk of infection in each classroom was estimated following the international method recommended by the federation of European Heating, Ventilation, and Air Conditioning Associations (REHVA). The probability of infection in all the cases studied was less than 14%. Therefore, this study provides a strong response against infections illnesses, such as Covid 19, in educational buildings where economic budgets of their facilities are low in both, maintenance and investment.


Human cadaveric study of subscapularis muscle innervation and guidelines to prevent denervation.
The upper and lower subscapular nerves provide innervation to the subscapularis muscle. However, the axillary nerve may provide a significant innervation to the lower portion of the muscle. The prevalence and patterns of anomalous innervation of the subscapularis muscle were studied to determine if these variations increased the risk of muscle denervation during open shoulder surgery. Twenty human cadaveric shoulders were dissected, and the innervation to the subscapularis was defined. The distance from the nerve insertion to the shoulder joint was measured in neutral and maximal external rotation. In the most common variation, the lower subscapular nerve arose from the axillary nerve (5 specimens; 25%). Although external rotation of the shoulder brought the nerve insertion significantly more lateral (35.2 to 16.9 mm, P < .001), the origin of the nerve had no significant effect on nerve proximity to the joint. The closeness of the nerve insertions to the shoulder joint warrants care during an anterior approach to the shoulder and dissections on the anterior surface of the muscle. Subscapularis nerve damage or denervation may cause unexplained joint instability and subscapularis dysfunction.


KLF4 deletion alters gastric cell lineage and induces MUC2 expression.
Gastric cancer is one of the most common types of cancer in the world, particularly in underdeveloped countries. The mechanism of gastric cancer is less understood compared with other types of gastrointestinal (GI) cancers. Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor and is a potential tumor suppressor in GI cancers. In this study, we have generated two mouse models, Rosa-Cre;Klf4(fl/fl) and Lgr5-Cre;Klf4(fl/fl). KLF4 was deleted by Rosa-Cre in the gastric epithelia cells or by Lgr5-Cre in the antral stem cells in the adult mice. KLF4 deletion resulted in increased proliferating cells and decreased pit mucous cells. Surprisingly, the intestinal goblet cell marker, MUC2, which is not expressed in normal gastric tissues, was strongly induced at the base of the KLF4-deleted antral glands. To understand the clinical relevance of these findings, we analyzed the expression of KLF4 and MUC2 in human gastric cancer. In a subset of human gastric cancer, the expression of KLF4 is negatively associated with MUC2 expression. In conclusion, KLF4 is essential for normal homeostasis of antral stem cells; loss of KLF4 and expression of MUC2 could be important markers for gastric cancer diagnosis.


[A new method for the determination of iron concentration in urine and its use in intramuscular iron load for the reliable and early detection of iron deficiency conditions].
A new laboratory technique for determining the urine iron concentration is described. By means of another new method, the so-called intramuscular iron loading test, any iron deficiency can be recognized at an early stage.


Acute eosinophilic pneumonia accompanied with COVID-19: a case report.
We report a case of acute eosinophilic pneumonia (AEP) triggered by coronavirus disease 2019 (COVID-19) infection. A 77-year-old man experienced left-sided chest pain and shortness of breath. Reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) revealed a positive result, and he was treated with favipiravir, ciclesonide, and lascufloxacin, but he showed poor improvement. On the other hand, computed tomography (CT) images were atypical for COVID-19 infection, and the elevation of eosinophil was found in blood and the fluid obtained by bronchoscopy. So, we clinically diagnosed this case as AEP. Administration of prednisolone dramatically improved the patient's clinical condition and chest radiograph findings, which were consistent with the clinical course of AEP. This case suggests the importance of considering the complications of AEP when treating patients with COVID-19 infection.


Pregranulosa cell-derived FGF23 protects oocytes from premature apoptosis during primordial follicle formation by inhibiting p38 MAPK in mice.
A large number of oocytes in the perinatal ovary in rodents get lost for unknown reasons. The granulosa cell-oocyte mutual communication is pivotal for directing formation of the primordial follicle; however, little is known if paracrine factors participate in modulating programmed oocyte death perinatally. We report here that pregranulosa cell-derived fibroblast growth factor 23 (FGF23) functioned in preventing oocyte apoptosis in the perinatal mouse ovary. Our results showed that FGF23 was exclusively expressed in pregranulosa cells, while fibroblast growth factor receptors (FGFRs) were specifically expressed in the oocytes in perinatal ovaries. FGFR1 was one of the representative receptors in mediating FGF23 signaling during the formation of the primordial follicle. In cultured ovaries, the number of live oocytes declines significantly, accompanied by the activation of the p38 mitogen-activated protein kinase signaling pathway, under the condition of FGFR1 disruption by specific inhibitors of FGFR1 or silencing of Fgf23. As a result, oocyte apoptosis increased and eventually led to a decrease in the number of germ cells in perinatal ovaries following the treatments. In the perinatal mouse ovary, pregranulosa cell-derived FGF23 binds to FGFR1 and activates at least the p38 mitogen-activated protein kinase signaling pathway, thereby regulating the level of apoptosis during primordial follicle formation. This study reemphasizes the importance of granulosa cell-oocyte mutual communication in modulating primordial follicle formation and supporting oocyte survival under physiological conditions.


Lack of significant effect of carboxyl-terminal parathyroid hormone-related peptide fragments on isolated rat and chick osteoclasts.
Parathyroid hormone-related protein (PTHrP) fragments 107-111, 107-138, and 107-139 were all found to be without consistent significant inhibitory effect on the resorptive activity of isolated rat and chick osteoclasts over the dose range 10(-13) M-10(-9) M. In the rat, these results contrasted with a strong and significant inhibition (100%) by calcitonin. Our results differ from that previously reported for C-terminal fragments of PTHrP by Fenton et al. [1-3], who noted up to a 70% inhibition of resorptive activity of isolated rat or chick osteoclasts at femtomolar doses and greater. It is possible that the lack of response observed in our osteoclast assays is due to unknown variables in the bone slice assay that influence the responsiveness of isolated osteoclasts to these fragments.


Charles Burstein, MD: First Director of Anesthesiology at Hospital for Special Surgery.
Charles L. Burstein was the first departmental Director and Chief of Anesthesiology at the Hospital for Special Surgery in New York City. He joined the staff in 1937, when the hospital was still known by its original name of the Hospital for the Ruptured and Crippled. In 1940, it was renamed The Hospital for Special Surgery. Burstein, an early disciple of Emery Rovenstine, accomplished much to advance the Department of Anesthesiology through academic collaborations, education, clinical specialization, and research. He laid the groundwork for the future success of a department that continues to thrive to this day in clinical and academic orthopedic anesthesia.


SBOL Visual: A Graphical Language for Genetic Designs.
Synthetic Biology Open Language (SBOL) Visual is a graphical standard for genetic engineering. It consists of symbols representing DNA subsequences, including regulatory elements and DNA assembly features. These symbols can be used to draw illustrations for communication and instruction, and as image assets for computer-aided design. SBOL Visual is a community standard, freely available for personal, academic, and commercial use (Creative Commons CC0 license). We provide prototypical symbol images that have been used in scientific publications and software tools. We encourage users to use and modify them freely, and to join the SBOL Visual community: http://www.sbolstandard.org/visual.


Jurors' perceptions of forensic science expert witnesses: Experience, qualifications, testimony style and credibility.
The judicial system calls upon expert witnesses to testify in court when complex or specialized knowledge, beyond that of the lay person, is needed to interpret the evidence. Previous research has indicated that particular traits of the expert witness can affect their credibility in the eyes of the jury, however most of this research has been undertaken using mock jurors. In contrast, this study investigated the perceptions of real jurors. In particular, the research focused on the juror's perception of the forensic scientists' expertise and credibility during testimony in homicide cases. Data was gathered from jurors after nine homicide trials using both questionnaire (n=29) and direct one to one interviews (n=22). The jurors defined what they thought an expert witness was and what attributes were important in a forensic scientist. Jurors suggested that the expert witness's education and years of experience were more important than certification or laboratory accreditation. The jurors' perceptions of the credibility of the expert was based upon the academic qualifications of the expert, the confidence they portrayed in answering the questions ask of them, their demeanor and their status of being government employee. The use of narrative language and demonstrative aids by the forensic science expert witness to explain the evidence was explored. Jurors described a deeper understanding as a result of narrative testimony and this was reported to be a key factor in the juror's acceptance that the witness was credible.


Isolation and characterization of two binding proteins for advanced glycosylation end products from bovine lung which are present on the endothelial cell surface.
Nonenzymatic glycosylation of proteins, as occurs at an accelerated rate in diabetes, can lead to the formation of advanced glycosylation end products of proteins (AGEs), which can bind to endothelial cells, thereby altering cellular function in a manner which could contribute to the pathogenesis of diabetic angiopathy. In this report, we describe the isolation of two endothelial cell surface-associated proteins which mediate, at least in part, the interaction of AGEs with endothelium. Based on pilot studies demonstrating AGE binding activity with comparable characteristics in bovine endothelial cell and lung extracts, the material from lung was sequentially subjected to chromatography on hydroxylapatite, fast protein liquid chromatography Mono S, and gel filtration. Two distinct polypeptides, approximately 35 and approximately 80 kDa, were purified to homogeneity, each of which bound AGEs as demonstrated by competitive binding assays using cellular binding proteins immobilized on a plastic surface. NH2-terminal sequence analysis indicated that the approximately 35-kDa protein was novel, whereas the NH2-terminal sequence of the approximately 80-kDa protein was identical to that of lactoferrin. Immunocytologic studies using polyclonal antibody prepared to each of the purified polypeptides demonstrated the presence of immunoreactive material on the surface of bovine endothelial cells maintained under serum-free conditions. Furthermore, immunoelectron microscopic studies with antibodies to the approximately 35- and approximately 80-kDa AGE-binding proteins conjugated to different size colloidal gold particles confirmed the presence of the target antigens on the cell surface and suggested that they were closely associated. IgG purified from polyclonal antisera to either the 35- or 80-kDa AGE-binding proteins blocked the binding of 125I-AGE-albumin to the cell surface. These results indicate that endothelial cells express specific cell surface molecules which mediate AGE-endothelial interaction. These polypeptides represent a novel class of cell surface acceptor molecules for glucose-modified proteins which may promote degradation and/or transcytosis of the ligand, and modulation of cellular function.


Key Components of Antenatal Lifestyle Interventions to Optimize Gestational Weight Gain: Secondary Analysis of a Systematic Review.
Randomized clinical trials have found that antenatal lifestyle interventions optimize gestational weight gain (GWG) and pregnancy outcomes. However, key components of successful interventions for implementation have not been systematically identified. To evaluate intervention components using the Template for Intervention Description and Replication (TIDieR) framework to inform implementation of antenatal lifestyle interventions in routine antenatal care. Included studies were drawn from a recently published systematic review on the efficacy of antenatal lifestyle interventions for optimizing GWG. The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, MEDLINE, and Embase were searched from January 1990 to May 2020. Randomized clinical trials examining efficacy of antenatal lifestyle interventions in optimizing GWG were included. Random effects meta-analyses were used to evaluate the association of intervention characteristics with efficacy of antenatal lifestyle interventions in optimizing GWG. The results are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Data extraction was performed by 2 independent reviewers. The main outcome was mean GWG. Measures included characteristics of antenatal lifestyle interventions comprising domains related to theoretical framework, material, procedure, facilitator (allied health staff, medical staff, or researcher), delivery format (individual or group), mode, location, gestational age at commencement (<20 wk or ≥20 wk), number of sessions (low [1-5 sessions], moderate [6-20 sessions], and high [≥21 sessions]), duration (low [1-12 wk], moderate [13-20 wk], and high [≥21 wk]), tailoring, attrition, and adherence. For all mean differences (MDs), the reference group was the control group (ie, usual care). Overall, 99 studies with 34 546 pregnant individuals were included with differential effective intervention components found according to intervention type. Broadly, interventions delivered by an allied health professional were associated with a greater decrease in GWG compared with those delivered by other facilitators (MD, -1.36 kg; 95% CI, -1.71 to -1.02 kg; P < .001). Compared with corresponding subgroups, dietary interventions with an individual delivery format (MD, -3.91 kg; 95% CI -5.82 to -2.01 kg; P = .002) and moderate number of sessions (MD, -4.35 kg; 95% CI -5.80 to -2.89 kg; P < .001) were associated with the greatest decrease in GWG. Physical activity and mixed behavioral interventions had attenuated associations with GWG. These interventions may benefit from an earlier commencement and a longer duration for more effective optimization of GWG. These findings suggest that pragmatic research may be needed to test and evaluate effective intervention components to inform implementation of interventions in routine antenatal care for broad public health benefit.


Df(h22q11)/+ mouse model exhibits reduced binding levels of GABAA receptors and structural and functional dysregulation in the inhibitory and excitatory networks of hippocampus.
The 22q11.2 hemizygous deletion confers high risk for multiple neurodevelopmental disorders. Inhibitory signaling, largely regulated through GABAA receptors, is suggested to serve a multitude of brain functions that are disrupted in the 22q11.2 deletion syndrome. We investigated the putative deficit of GABAA receptors and the potential substrates contributing to the inhibitory and excitatory dysregulations in hippocampal networks of the Df(h22q11)/+ mouse model of the 22q11.2 hemizygous deletion. The Df(h22q11)/+ mice exhibited impairments in several hippocampus-related functional domains, represented by impaired spatial memory and sensory gating functions. Autoradiography using the [3H]muscimol tracer revealed a significant reduction in GABAA receptor binding in the CA1 and CA3 subregions, together with a loss of GAD67+ interneurons in CA1 of Df(h22q11)/+ mice. Furthermore, electrophysiology recordings exhibited significantly higher neuronal activity in CA3, in response to the GABAA receptor antagonist, bicuculline, as compared with wild type mice. Density and volume of dendritic spines in pyramidal neurons were reduced and Sholl analysis also showed a reduction in the complexity of basal dendritic tree in CA1 and CA3 subregions of Df(h22q11)/+ mice. Overall, our findings demonstrate that hemizygous deletion in the 22q11.2 locus leads to dysregulations in the inhibitory circuits, involving reduced binding levels of GABAA receptors, in addition to functional and structural modulations of the excitatory networks of hippocampus.


Mitochondria-targeted DsRed2 protein expression during the early stage of bovine somatic cell nuclear transfer embryo development.
Somatic cell nuclear transfer (SCNT) has been widely used as an efficient tool in biomedical research for the generation of transgenic animals from somatic cells with genetic modifications. Although remarkable advances in SCNT techniques have been reported in a variety of mammals, the cloning efficiency in domestic animals is still low due to the developmental defects of SCNT embryos. In particular, recent evidence has revealed that mitochondrial dysfunction is detected during the early development of SCNT embryos. However, there have been relatively few or no studies regarding the development of a system for evaluating mitochondrial behavior or dynamics. For the first time, in mitochondria of bovine SCNT embryos, we developed a method for the visualization of mitochondria and expression of fluorescence proteins. To express red fluorescence in mitochondria of cloned embryos, bovine ear skin fibroblasts, nuclear donor, were stably transfected with a vector carrying mitochondria-targeting DsRed2 gene tagged with V5 epitope (mito-DsRed2-V5 tag) using lentivirus-mediated gene transfer because of its ability to integrate in the cell genome and the potential for long-term transgene expression in the transduced cells and their dividing cells. From western blotting analysis of V5 tag protein using mitochondrial fraction and confocal microscopy of red fluorescence using SCNT embryos, we found that the mitochondrial expression of the mito-DsRed2 protein was detected until the blastocyst stage. In addition, according to image analysis, it may be suggested possible use of the system for visualization of mitochondrial localization and evaluation of mitochondrial behaviors or dynamics in early development of bovine SCNT embryos.


Life satisfaction of couples 3 years after stroke.
To compare the life satisfaction of stroke patients to that of their spouses, and to examine spouses' variables as determinants of the patients' life satisfaction. Patients with a first-ever stroke who were admitted to an inpatient rehabilitation centre and their spouses were included (n=78 couples). Measurements took place 3 years after the stroke. Life satisfaction was measured using the Life Satisfaction Questionnaire (LiSat-9). More spouses (50%) than patients (28%) were dissatisfied with their life as a whole. Spouses were also more likely to be dissatisfied with all other domains of life satisfaction than patients. The associations between the life satisfaction of patients and of spouses were weak (Cramer's V 0.00-0.43). In the backward linear regression analysis both patients' participation in social activities and spouses' life satisfaction were significantly related to patients' life satisfaction. A total of 17.8% of the variance of patients' life satisfaction could be explained by the model. Both spouse and patient in a couple experience decreased life satisfaction in the chronic phase after stroke, spouses even more so than patients. The life satisfaction of stroke patients was significantly related to spouses' life satisfaction. Family-centred care should be an important part of the rehabilitation process. [ • Both spouse and patient in a couple experience decreased life satisfaction in the chronic phase after stroke.• The life satisfaction of stroke patients was significantly related to spouses' life satisfaction.• Family-centred care, in which the spouse is closely involved, should be an important part of the rehabilitation process.]


Meridional binocular rivalry reveals a trace of uncorrected oblique input during development in the adult brain.
Binocular rivalry (BR) is a visual perception phenomenon that occurs when each eye perceives different images and stimuli, causing alternating monocular dominance. To measure BR, many studies have used two monocular conflicting images to induce monocular alternations. Here we chose a group of participants with oblique astigmatism (OA) and who produced blur on the orthogonal oblique meridian in each eye, resulting in two conflicting images, which may enhance the stimulation of monocular alternations. Our results show that OA participants tend to have a high rate of BR when viewing natural images, whereas the control group does not have BR for the same images. We suggest that this low ability to fuse could indicate the presence of a trace due to uncorrected vision during the critical period, which could be retained in the adult brain.


Various types of stem cells, including a population of very small embryonic-like stem cells, are mobilized into peripheral blood in patients with Crohn's disease.
Developmentally early cells, including hematopoietic stem progenitor cells (HSPCs), mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), and very small embryonic-like stem cells (VSELs), are mobilized into peripheral blood (PB) in response to tissue/organ injury. We sought to determine whether these cells are mobilized into PB in patients with Crohn's disease (CD). Twenty-five patients with active CD, 20 patients in clinical remission, and 25 age-matched controls were recruited and PB samples harvested. The circulating CD133+/Lin-/CD45+ and CD34+/Lin-/CD45+ cells enriched for HSPCs, CD105+/STRO-1+/CD45- cells enriched for MSCs, CD34+/KDR+/CD31+/CD45-cells enriched for EPCs, and small CXCR4+CD34+CD133+ subsets of Lin-CD45- cells that correspond to the population of VSELs were counted by fluorescence-activated cell sorting (FACS) and evaluated by direct immunofluorescence staining for pluripotency embryonic markers and by reverse-transcription polymerase chain reaction (RT-PCR) for expression of messenger (m)RNAs for a panel of genes expressed in intestine epithelial stem cells. The serum concentration of factors involved in stem cell trafficking, such as stromal derived factor-1 (SDF-1), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) were measured by enzyme-linked immunosorbent assay (ELISA). Our data indicate that cells expressing markers for MSCs, EPCs, and small Oct-4+Nanog+SSEA-4+CXCR4+lin-CD45- VSELs are mobilized into PB in CD. The mobilized cells also expressed at the mRNA level genes playing a role in development and regeneration of gastrointestinal epithelium. All these changes were accompanied by increased serum concentrations of VEGF and HGF. CD triggers the mobilization of MSCs, EPCs, and VSELs, while the significance and precise role of these mobilized cells in repair of damaged intestine requires further study.


[Use of synthetic slings and mesh implants in the treatment of female stress urinary incontinence and prolapse : Statement of the Working Group on Urological Functional Diagnostics and Female Urology of the Academy of the German Society of Urology].
Due to a safety alert issued by the US Food and Drug Administration (FDA) in 2011 for transvaginal mesh implants to treat female prolapse as a result of numerous reports of complications such as infection, chronic pain, dyspareunia, vaginal erosion, shrinkage and erosion into other organs nearly all industrial products have been withdrawn from the market in the meantime. The United Kingdom, Australia, and New Zealand extended warnings and prohibitions even on the implantation of midurethral slings (TVT, TOT). In view of these current international controversies regarding the use of implanted materials for the treatment of stress incontinence and prolapse and the lack of clear guidelines for the use of biomaterials, the opinion of the Working Group on Urological Functional Diagnostics and Female Urology should provide clarity. The Opinion is based on the SCENIHR Report of the "European Commission's Scientific Committee on Emerging and Newly Identified Health Risks", the "Consensus Statement of the European Urology Association and the European Urogynaecological Association on the Use of Implanted Materials for Treating Pelvic Organ Prolapse and Stress Urinary Incontinence" and in compliance with relevant EAU and national guidelines and the opinion of the Association for Urogynaecology and Plastic Pelvic Floor Reconstruction (AGUB eV). In addition, recommendations are given for the future handling of implants of slings and meshes for the treatment of stress incontinence and prolapse from a urologic viewpoint.


Corticotroph cell hyperplasia in a patient with Addison disease: case report.
A woman with Addison disease developed hyperpigmentation, headache, and nausea despite conventional replacement therapy with cortisone. Excessively elevated plasma adrenocorticotropic hormone (ACTH) with absence of response to administration of corticotropin-releasing factor (CRF), and roentgenological evidence of enlargement of the sella turcica, as well as detection of enlarged pituitary gland on magnetic resonance images, led to a diagnosis of ACTH-producing microadenoma, which was removed by transsphenoidal microsurgery. The specimen obtained at surgery evidenced corticotroph hyperplasia, as demonstrated by immunohistochemical staining for ACTH. Fine structure exhibited densely granulated cells with a few bundles of microfilaments and an abundance of large lysosomal bodies. Surgical removal of the hyperplasia alleviated the patient's symptoms, and hyperpigmentation faded remarkably. Her plasma ACTH level returned to normal, has remained normal for more than 3 years, and responds adequately to CRF administration.


Liposome Bupivacaine for Postsurgical Analgesia in Patients Undergoing Robotically Assisted Cardiac Surgery.
Despite the advantages of robotically assisted cardiac surgery over conventional open sternotomy, robotically assisted surgery may be associated with substantial postsurgical pain arising from multiple incisions and access ports. This single-site, retrospective chart review evaluated the impact of liposome bupivacaine compared with bupivacaine HCl on postsurgical pain management in patients undergoing robotically assisted endoscopic cardiac surgery. Sequential patient cohorts undergoing robotically assisted cardiac surgery received either 0.25% bupivacaine HCl (100 mg in 40 mL, n = 30) or liposome bupivacaine (266 mg in 20 mL, expanded to 40 mL with 0.9% sterile normal saline, n = 30) intraoperatively via equal-volume infiltration across port sites. Outcome measures, collected from the day of surgery through postoperative day 3, were daily and total use of opioid analgesics (converted to morphine equivalents), pain intensity (11-point numeric rating scale), and incidence of postoperative nausea and vomiting. Median length of hospital stay was 4 days in the liposome bupivacaine group and 3 days in the bupivacaine HCl group. Patients receiving liposome bupivacaine had numerically lower mean pain scores (at six of seven time points), reduced mean opioid consumption, and a reduced incidence of postoperative nausea and vomiting compared with those receiving bupivacaine HCl, although none of the differences reached statistical significance. Results from this small retrospective, observational study suggest that liposome bupivacaine may improve postsurgical pain relief and reduce postsurgical opioid consumption, in comparison with bupivacaine HCl, in patients undergoing robotically assisted cardiac surgery. Larger prospective studies of liposome bupivacaine in this setting are warranted.


Modeling the Cost-Utility of Treatment Sequences for Multiple Sclerosis.
Most patients with multiple sclerosis (MS) switch between disease-modifying therapies (DMTs) during their lifetime. Our aim was to develop an MS cost-utility model that takes treatment switching into account to provide a more realistic estimate of treatment benefit than previous models that assume lifetime use of 1 DMT. A treatment sequence model using a microsimulation framework with a lifetime time horizon and a societal perspective was developed in R. Clinical plausibility and decision rules for switching were defined in consultation with Dutch MS neurologists. The ability of DMTs to prevent relapses and delay disease progression was modeled by applying DMT-specific estimates derived from a network meta-analysis of randomized controlled trials to natural history data. A total of 2 treatment strategies were compared: a first-line DMT sequence (peginterferon-glatiramer-teriflunomide-interferon-beta-dimethyl fumarate) and an escalation DMT sequence (peginterferon-glatiramer-ocrelizumab-natalizumab-alemtuzumab). Scenario analyses explored impact of alternative sources of natural history data, societal versus healthcare perspective, and condition-specific versus generic utilities. Predicted short-term switches (<5 years) were externally validated with Dutch claims data on DMT use. Short-term switches predicted by the model compared well with Dutch claims data. Transition from relapsing-remitting MS to secondary progressive MS was delayed by the escalation sequence (24.7 vs 20.3 years on first-line sequence). Model results were sensitive to utility values and medical resource consumption was a large driver of uncertainty. This microsimulation model overcomes the limitation of previous models by modeling treatment sequences. Because it better reflects clinical reality, it facilitates incorporating cost-utility information in clinical guidelines.


Identical QRS complexes during atrial fibrillation with aberrant conduction and ventricular tachycardia. The value of a His bundle recording.
In a patient with chronic congestive heart failure, right bundle branch block-shaped QRS complexes occurred in salvos during atrial fibrillation. The site of origin of these complexes could not be determined from the 12-lead ECG alone. Recording of a His bundle electrogram showed that both intraventricular aberrant conduction and ventricular tachycardia were responsible for salvos having the same QRS complexes in the 12-lead ECG.


The clinical rate of antibiotic change following empiric treatment for suspected urinary tract infections.
To determine the rate of antibiotic change in an outpatient setting following empiric treatment of culture proven UTI and to identify risk factors associated with change. Patients with suspected UTI and urine culture were reviewed (January 2016-June 2016). Those with a positive culture were categorized by whether or not they were treated empirically. Empiric treatment was evaluated for associations with clinical-demographic data, symptoms and urinalysis (UA). Antibiotic change was evaluated with clinical-demographic data, urine culture, and resistance patterns. 916 urine cultures (636 patients) were included. 391 (43%) cultures were positive, and 164 (42%) were treated empirically. Clinical-demographic data did not differ between groups. Those treated empirically had more documented UTI symptoms (93 vs 58%, P < 0.001), and UA abnormalities including positive nitrites (51 vs 29%, P < 0.001), 3 + leukocyte esterase (27 vs 19%, P = 0.002) and 3 + blood (13 vs 4%, P = 0.005). Of those treated empirically, 42/164 (26%) required an antibiotic change, and this was associated with immunosuppression (12 vs 2%, P = 0.027) resistance to > 3 antibiotics (33 vs 20%, P = 0.039) and also resistance to fluoroquinolone (50 vs 30%, P = 0.016), monobactam (19 vs 7% P = 0.042) and TMP-SMX (52 vs 19%, P < 0.001). Almost one-quarter of patients treated empirically required antibiotic change. This was driven largely by bacterial resistance. New technologies allowing rapid bacterial identification and sensitivity may improve patient care.


Use of gold nanoparticle-coated sorbent materials for the selective preconcentration of sulfonylurea herbicides in water samples and determination by capillary liquid chromatography.
Two new gold nanoparticle (NP) coated materials (silica supported on gold NP with and without ionic liquid) were synthesized for solid phase extraction of sulfonylurea herbicides (SUHs), such as bensulfuron-methyl (BSM), metsulfuron-methyl (MSM), pyrazosulfuron-methyl (PSM), thifensulfuron-methyl (TFM) and triasulfuron (TS), from water samples, followed by capillary liquid chromatography coupled to diode array detection (CLC-DAD). Several factors influencing the preconcentration efficiency of SUHs and its subsequent determination, such as pH of the sample, eluent and reusability of sorbents, have been investigated. Under the optimum conditions, the developed method allowed the determination of BSM, MSM, PSM, TFM and TS in a linear range between 0.05 and 1.00 μg mL(-1), with relative standard deviation values lower than 4.5% (n=10), in all cases. Detection limits within 0.002-0.009 μg mL(-1) range were achieved. The usefulness of the proposed method was demonstrated by the analysis of river water samples, in which recoveries between 83.9 and 105.0% were obtained. The Au-NP-ionic liquid-functionalized silica sorbent showed higher recoveries (selectivity) for the SUHs than the commercially available C18 sorbents.


Rosemary-stimulated reduction of DNA strand breaks and FPG-sensitive sites in mammalian cells treated with H2O2 or visible light-excited Methylene Blue.
In this study possible protective effects of rosemary against oxidative DNA damage induced by H2O2- and visible light-excited Methylene Blue in colon cancer cells CaCo-2 and hamster lung cells V79 were investigated. The level of DNA damage (DNA strand breaks) was measured using the classical and modified single cell gel electrophoresis, so-called comet assay. Our findings showed that an ethanol extract from rosemary reduced the genotoxic activity of both agents after a long-term (24 h; 0.3 microg/ml) or short-term (2 h; 30 microg/ml) pre-incubation of cells. We suggest that the extract of rosemary exhibits a protective effect against oxidative damage to DNA as a consequence of scavenging of both *OH radicals and singlet oxygen ((1)O2).


Managing anterior capsule contraction by mechanical widening with vitrector-cut capsulotomy.
We present a technique, vitrectorhexis, in which a vitrector-cut capsulotomy is used to treat anterior capsule contraction syndrome. A vitrector handpiece is used to remove all fibrous capsule tissue and residual lens epithelial cells from the anterior chamber. Vitrectorhexis may be an alternative to neodymium:YAG laser capsulotomy as it decreases the risk of radial tear extension to the zonules and of secondary IOL decentration. The technique was used in a 77-year-old man with capsulorhexis contraction syndrome and extensive fibrosis after phacoemulsification with silicone piggyback intraocular lens implantation. One day postoperatively, visual acuity improved from 20/60 to 20/30 and the anterior chamber reaction was minimal. At 1 month, best corrected visual acuity was 20/20. The IOL was well centered at 6 months.


Implementation of a manual for working with wobbler mice and criteria for discontinuation of the experiment.
Mouse breeding is of importance to a whole range of medical and biological research. There are many known mouse models for motor neuron diseases. However, it must be kept in mind that especially mouse models for amyotrophic lateral sclerosis develop severe symptoms causing intense stress. This article is designed to summarize conscientious work with the wobbler mouse, a model for the sporadic form of amyotrophic lateral sclerosis. This mouse model is characterized by a degeneration of α-motor-neurons leading to head tremor, loss of body weight and rapidly progressive paralysis. Although this mouse model has been known since 1956, there are no guidelines for breeding wobbler mice. Due to the lack of such guidelines the present study tries to close this gap and implements a manual for further studies. It includes the whole workflow in regard to wobbler mice from breeding and animal care taking, genotyping and phenotype analysis, but also gives some examples for the use of various neuronal tissues for histological investigation. Beside the progress in research a second aim should always be the enhancement of mouse welfare and reduction of stress for the laboratory animals.


Atypical simple bone cysts of the jaws. I: Recurrent lesions.
The aetiology, clinical and radiographic features and the treatment of simple bone cysts of the jaws are discussed. Recurrence of jaw lesions is unusual. Two cases are presented of simple bone cyst in the mandible which recurred following conventional treatment. The importance of clinical and radiographic follow-up is emphasised.


Paclitaxel prevented restenosis in a totally occluded small vessel with in-stent restenosis: a 9-month angiographic follow-up.
We present a case of a 57-year-old patient who underwent multiple percutaneous coronary interventions for a lesion at the graft anastomosis to his first obtuse marginal branch. After initial angiographic success with multiple treatment modalities (excluding intravascular brachytherapy because of prior mantle radiation), restenosis or reocclusion eventuated on each occasion. Two paclitaxel-coated stents were implanted in this small vessel with diffuse in-stent restenosis and recurrent total occlusion. Complete patency was documented on a 9-month angiographic follow-up.


Incidentally Detected 131-Iodine Avid Parotid Oncocytoma Coexistent with Papillary Carcinoma Thyroid.
131-I radioactive iodine (RAI) scan is an important modality in the management of differentiated thyroid cancer to detect recurrent or residual disease. Thus it is important to have knowledge about the possibility of false positive findings in these scans to avoid wrongful diagnosis and unnecessary treatment. We here by present a patient who underwent total thyroidectomy with lymph node dissection and followed by radioactive iodine therapy for papillary thyroid cancer. He had 131-I iodine avid nodular lesion in the left parotid gland which was later proven to be oncocytoma on histopathology. False positive findings on radioactive iodine scans are a possibility which should be known to surgeons as well as nuclear medicine physicians for accurate diagnosis and appropriate management.


Chloroquine disposition in hypersensitive and non-hypersensitive subjects and its significance in chloroquine-induced pruritus.
Twenty-one healthy Nigerian volunteers distributed into four groups participated in a study to determine the significance of chloroquine disposition in chloroquine-induced pruritus. It involved the administration of chloroquine with or without promethazine pre-administration to the subjects. Group I consisted of 8 chloroquine non-hypersensitive subjects receiving 2 tablets of chloroquine sulphate (300 mg base); Group II consisted of 5 chloroquine non-hypersensitive subjects receiving 2 tablets of chloroquine sulphate 30 minutes after 25 mg promethazine tablet pre-administration; Group III consisted of 5 chloroquine hypersensitive subjects treated as in Group II; Group IV consisted of 3 hypersensitive subjects treated as in Group I. Blood (5 ml) and urine samples were collected periodically for up to 6 days post-dose. The samples were analysed for chloroquine and some of its oxidation metabolites by a specific HPLC method. Probit plots of cumulative drug/metabolite ratios were done to determine if there is polymorphism in chloroquine metabolism. There was bimodality only in the distribution of chloroquine/monodesethylchloroquine ratios, suggesting polymorphism in the metabolic oxidation of chloroquine in these subjects. Higher levels of monodesethylchloroquine were obtained in Group IV subjects when compared with any of the other groups. The oral clearance rate, elimination half-life, and volume distribution at steady state of chloroquine in the study groups were not significantly different (P greater than 0.05). In the absence of promethazine there appears to be an extensive metabolism of chloroquine in hypersensitive individuals to produce monodesethylchloroquine which probably determines the degree of pruritus experienced by an individual.


Variants of the superior labrum and labro-bicipital complex: a comparative study of shoulder specimens using MR arthrography, multi-slice CT arthrography and anatomical dissection.
The purpose of the present study was to evaluate the anatomical variability of the superior labrum and to compare the value of MR arthrography and multi-slice CT arthrography in the diagnosis of variants of the labro-bicipital complex. Forty-three human shoulder specimens (age range and mean age at death, 61-89 years and 78.3 years) were examined with the use of MR arthrography and multi-slice CT arthrography prior to joint exploration and macroscopic inspection of the superior labrum and labro-bicipital complex. Two radiologists evaluated MR and CT arthrograms, and the results were compared with macroscopic assessments. Anatomical dissection of all shoulder specimens revealed a sublabral recess in 32/43 (74%) cases. The attachment of the superior labrum was categorised as type 1 in ten (23%) cases, as type 2 in eight (19%), as type 3 in ten (23%), and as type 4 in 14 (33%) cases. One superior labrum showed detachment consistent with a superior labral anteroposterior (SLAP) type 3 lesion. On MR arthrography and CT arthrography the attachment of the superior labrum was categorised in concordance with macroscopic assessments in 79% and 84% of cases, respectively. The anteroposterior extension of sublabral recesses was accurately determined with MR and CT arthrography in 59% and 81% of cases, respectively. The attachment of the superior labrum shows considerable variability. Thus, exact depiction of variants is essential in order to avoid the false positive diagnosis of a superior labral tear (SLAP or Andrews lesion). Both, MR arthrography and multi-slice CT arthrography were effective in the detection and classification of sublabral recesses.


Immunohistochemistry of gamma-aminobutyric acid in the cat nucleus tractus solitarius.
Using a new antibody directed solely against the gamma-aminobutyric acid (GABA) molecule, distribution of GABA was studied in the nucleus tractus solitarii of the cat. Both immunoreactive puncta and cell bodies had a homogenous distribution within the nucleus. The one exception was in the parvocellular subdivision where very little immunoreactive puncta, but numerous immunoreactive cell bodies, were found. Results of this investigation provide immunohistochemical evidence of GABA's localization in an autonomic nucleus involved in cardiovascular regulation.


Odorant-induced brain activation as a function of normal aging and Alzheimer's disease: A preliminary study.
Olfactory dysfunction consistently occurs in patients with Alzheimer's disease (AD), beyond the mild and gradual decline in olfactory ability found in normal aging. This dysfunction begins early in the disease course, typically before clinical diagnosis, and progresses with disease severity. While odor identification and detection deficits clearly differentiate AD from controls, there remains uncertainty as to whether these are determined by olfactory threshold. The purpose of the current preliminary fMRI study was to examine the neural correlates of olfactory processing in healthy young and old adults and compare them with AD patients. We also explored the interplay between age and disease-related psychophysical olfactory declines and odorant-induced brain activation. Results indicated AD patients had decreased odor detection task-related signal in all regions of the primary olfactory cortex, with activity in the entorhinal cortex best differentiating the groups. Moderated-mediation analyses on neuro-psychophysical relationships found that increased brain activation in the entorhinal cortex moderated the negative effect of disease-related threshold changes on olfactory detection. Therefore, even in the face of higher (worse) olfactory thresholds, older adults and AD patients compensated for this effect with increased brain activation in a primary olfactory brain region. This was the case for odor detection but not odor identification. fMRI activation induced by an olfactory detection task may eventually be useful in improving early discovery of AD and may, eventually, facilitate early treatment interventions in subjects at risk for AD.