Salvage of Combat Hindfoot Fractures in 2003-2014 UK Military.
Hindfoot fractures pose a considerable challenge to military orthopaedic surgeons, as combat injuries are typically the result of energy transfers not seen in civilian practice. This study aimed to characterize the pattern of hindfoot injuries sustained by UK military casualties in recent conflicts, define the early amputation and infection rate, and identify factors associated with poor early outcomes. The UK Joint Theatre Trauma Registry was searched for British military casualties sustaining a hindfoot fracture from Iraq and Afghanistan between 2003 and 2014. Data on the injury pattern and management were obtained along with 18-month follow-up data. Statistical analysis was performed with the chi-square test and binomial logistic regression analysis. The threshold for significance was set at P < .05. One hundred fourteen patients sustained 134 hindfoot injuries. Eighteen-month follow-up was available for 92 patients (81%) and 114 hindfeet (85%). The calcaneus was fractured in 116 cases (87%): 54 (47%) were managed conservatively, 32 (28%) underwent K-wire fixation, and 30 (26%) underwent internal fixation. Nineteen patients (17%) required transtibial amputation during this time. A deep infection requiring operative treatment occurred in 13 cases (11%) with Staphylococcus aureus, the most common infectious organism (46%). A deep infection was strongly associated with operative fracture management ( P = .0016). When controlling for multiple variables, the presence of a deep infection was significantly associated with a requirement for amputation at 18 months ( P = .023). There was no association between open fractures and a requirement for amputation at 18 months ( P = .640), nor was conservative management associated with a requirement for amputation ( P = .999). Thirty-six fractures (32%) required unplanned revision surgery within the first 18 months following salvage, of which 19 (53%) involved amputation. A deep infection was the sole variable significantly associated with a requirement for amputation by 18 months. These results suggest that attempts at salvaging these injuries are at the limits of orthopaedic technical feasibility. Level III, comparative series.


Effect of steam and lactic acid treatments on the survival of Salmonella Enteritidis and Campylobacter jejuni inoculated on chicken skin.
Campylobacteriosis and salmonellosis are the most frequently reported zoonotic infectious diseases. The present work evaluated the effectiveness of steam treatment at 100 °C for 8s, a 5% lactic acid treatment for 1 min and their combination for inactivating Salmonella Enteritidis and Campylobacter jejuni inoculated on chicken skin. The impact of each treatment on the total aerobic mesophilic bacteria and the effect of rinsing after contact with lactic acid were also evaluated. Residual bacteria were counted immediately after treatment or after seven days of storage at 4 °C. Results demonstrated the immediate efficiency of the steam and the combined treatments with reductions of approximately 6 and 5 log cfu/cm2 respectively for S. Enteritidis and C. jejuni. They also showed significant reductions (equal to or >3.2 log cfu/cm2) in the total aerobic mesophilic plate count. Lactic acid had a persistent effect on pathogen growth during storage which was significantly higher when the skin was not rinsed, reaching reductions of 3.8 log cfu/cm2 for both S. Enteritidis and C. jejuni. Only the combined treatments significantly reduced the recovery of the total aerobic mesophilic bacteria during storage. The significant reductions in both pathogens and total aerobic mesophilic bacteria on treated chicken skins are possible ways to improve the safety and shelf life of the product although high levels of indigenous non-pathogenic bacteria may be beneficial due to their protective effect against potential re-contamination of chicken skin.


Temporoparietal osteofascial flap for head and neck reconstruction.
This article describes the use of the temporoparietal osteofascial flap (TOF) for reconstruction of bony defects in the midface and mandible. We reviewed the demographics, etiology, indications, surgical technique, radiographic evaluation, and final outcome of 11 patients with upper or lower jaw defects who underwent reconstruction using the TOF between 1994 and 1999. The TOF was used to reconstruct a defect of the mandible in 7 patients, the hard palate in 2 patients, the maxilla in 1 patient, and the zygoma in 1 patient. The defect was a result of tumor resection in 9 patients and of trauma in 2 patients. The defect size ranged from 3 to 6 cm. Ten flaps (91%) were successful and 1 flap failed. There was 1 donor site complication (small dural tear) that was repaired immediately without sequelae. One patient had osseointegrated dental implants placed in the bone with good results. Exploration of the construction area was performed in 1 patient 13 months after surgery because of recurrent tumor. It showed a fully integrated bone flap. This vascularized calvarial bone flap can be used for the reconstruction of small to medium-sized defects of the maxilla and lateral mandible with good functional and cosmetic results. It can be performed without special microvascular expertise and with minimal donor site morbidity. A full-thickness bone flap can support osseointegrated dental implants.


Ertapenem: a review of its use in the treatment of bacterial infections.
The Group 1, 1 beta-methyl carbapenem ertapenem (Invanz) is approved for parenteral use in patients with complicated intra-abdominal infection (cIAI), community-acquired pneumonia (CAP) and acute pelvic infection caused by susceptible strains of certain designated organisms in both the US and the EU. Additional approved indications in the US include complicated skin and skin structure infection (cSSSI) and complicated urinary tract infection (cUTI). Ertapenem is approved for use in adults in both the US and the EU and in paediatric patients aged >or=3 months in the US. Ertapenem has a broad spectrum of in vitro activity against Gram-negative pathogens, including extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae, Gram-positive pathogens and anaerobic pathogens. It has similar efficacy to comparator antibacterials such as piperacillin/tazobactam in cSSSI (including diabetic foot infection), cIAI and acute pelvic infection and ceftriaxone with or without metronidazole in cIAI, cUTI and CAP. The drug has also shown efficacy in the treatment of paediatric patients with complicated community-acquired bacterial infections. Ertapenem has a convenient once-daily administration schedule and is generally well tolerated. Thus, ertapenem is an important option for the empirical treatment of complicated community-acquired bacterial infections in hospitalised patients.


EFFECTS OF ELEVATED ATMOSPHERIC CO(2) ON WATER CHEMISTRY AND MOSQUITO (DIPTERA: CULICIDAE) GROWTH UNDER COMPETITIVE CONDITIONS IN CONTAINER HABITATS.
We investigated the direct and indirect effects of elevated atmospheric CO(2) on freshwater container habitats and their larval mosquito occupants. We predicted that a doubling of atmospheric CO(2) would (1) alter the chemical properties of water in this system, (2) slow degradation of leaf litter, and (3) decrease larval growth of Aedes albopictus (Skuse) mosquitoes raised on that litter under competitive conditions. Effects of elevated CO(2) on water quality parameters were not detected, but the presence of leaf litter significantly reduced pH and dissolved oxygen relative to water-filled containers without litter. Degradation rates of oak leaf litter from plants grown under elevated CO(2) atmospheres did not differ from breakdown rates of litter from ambient CO(2) conditions. Litter from plants grown in an elevated CO(2) atmospheres did not influence mosquito population growth, but mosquito production decreased significantly with increasing larval density. Differences among mosquito density treatments influenced survivorship most strongly among male Ae. albopictus and time to emergence most strongly among females, suggesting fundamental sex-determined differences in response to competition. Results of this and other studies indicate that direct and indirect effects of doubled atmospheric CO(2) are minimal in artificial containers with freshwater.


Addressing consumer grievances in medicine: policies and practices of newborn screening programs in the United States.
Newborn screening programs collectively administer the largest genetic testing initiative in the United States. The redress of grievances is an important mechanism for consumers to provide input into clinical and public health programs. In this study, we evaluated mechanisms for addressing consumer grievances in newborn screening programs. To do this, we surveyed all 50 state plus the District of Columbia newborn screening programs by questionnaire regarding protocols for receipt and redress of problems reported by parents of newborns and ascertained the existence and nature of complaints and how complaints were documented and addressed. Pertinent state and federal legislation and regulation were also reviewed. Six of 49 newborn screening programs reported having formal policies for handling consumer grievances. Four states reported having pertinent legislation or regulation. Thirty-eight of 49 states reported having received complaints from 1993 to 1995. Thirteen of 49 newborn screening programs reported that they actively seek feedback from consumers. Consumer grievances ranged from minor complaints to potentially life-threatening concerns. In general, complaints are managed on an ad hoc basis; formal policies are typically lacking. As newborn screening programs affect a vast number of Americans, a proactive and comprehensive approach, including solicitation of consumer feedback, could benefit both newborn screening programs and the public served by them.


High-Efficiency Secretion of β-Mannanase in Bacillus subtilis through Protein Synthesis and Secretion Optimization.
The manno endo-1,4-mannosidase (β-mannanase, EC. 188.8.131.52) catalyzes the random hydrolysis of internal (1 → 4)-β-mannosidic linkages in the mannan polymers. A codon optimized β-mannanase gene from Bacillus licheniformis DSM13 was expressed in Bacillus subtilis. When four Sec-dependent and two Tat-dependent signal peptide sequences cloned from B. subtilis were placed upstream of the target gene, the highest activity of β-mannanase was observed using SPlipA as a signal peptide. Then a 1.25-fold activity of β-mannanase was obtained when another copy of groESL operon was inserted into the genome of host strain. Finally, five different promoters were separately used to enhance the synthesis of the target protein. The results showed that promoter Pmglv, a modified maltose-inducible promoter, significantly elevated the production of β-mannanase. After 72 h of flask fermentation, the enzyme activity of β-mannanase in the supernatant when using locust bean gum as substrate reached 2207 U/mL. This work provided a promising β-mannanase production strain in industrial application.


[Effects of isorhapotigenin and resveratrol on function of peripheral blood polymorphonuclear leukocytes from rabbits].
In effects of isorhapotigenin and resveratrol on chemotaxis and release of beta-glucuronidase from rabbit peripheral blood polymorphonuclear leukocytes stimulated with formylmethionyl-leucyl-phenyl-phenylalanine (fMLPP) were studied. The optimal concentration of fMLPP for the induction of chemotaxis of polymorphonuclear leukocytes was approximately at 5 x 10(-10) mol.L-1. fMLPP, at the concentration range of 10(-10)-10(-6) mol.L-1, dose-dependently increased the release of beta-glucuronidase from polymorphonuclear leukocytes. Isorhapotigenin and resveratrol both inhibited the chemotaxis of polymorphonuclear leukocytes stimulated with fMLPP(5 x 10(-10) mol.L-1). Isorhapotigenin, at the concentration range of 10(-5)-10(-4) mol.L-1, dose-dependently inhibited the release of beta-glucuronidase from polymorphonuclear leukocytes stimulated with fMLPP(10(-8) mol.L-1). Resveratrol, at the concentrations of 1 x 10(-5) and 3 x 10(-5) mol.L-1, was shown to dose-dependently inhibit beta-glucuronidase release from polymorphonuclear leukocytes stimulated with fMLPP(10(-8) mol.L-1).


Risk perceptions and changes in tobacco use in relation to Coronavirus Disease 2019 pandemic: A qualitative study on adolescent tobacco users in Hong Kong.
Tobacco use is associated with an increased risk of Coronavirus Disease 2019 (COVID-19) infection, severe COVID-19 outcomes requiring intensive care, and mortality. We investigated the perceived risk of and changes in cigarette, e-cigarette (EC) and heated tobacco product (HTP) use in relation to COVID-19 in Hong Kong adolescent tobacco users. We conducted semi-structured telephone interviews from January to April 2021 and in February 2022 on 40 adolescents (65% boys, Secondary school grades 2-6) who participated in our previous smoking surveys and were using cigarettes, ECs or HTPs before the first wave of the COVID-19 pandemic in January 2020. Adolescents generally perceived higher risks of contracting and having more severe COVID-19 from using cigarettes than ECs/HTPs, but they had limited knowledge of COVID-19 risks from EC/HTP use, particularly. Both increased and reduced consumption were found in tobacco, with EC use being the less affected product. Changes also included switching to ECs for convenience and lower cost and shifting from smoking cigarettes outside to mainly at home or in hidden areas. COVID-related policies, fear of infection, non-COVID-related health concerns, less social opportunities and pocket money, and limited access to tobacco products were barriers to tobacco use. In contrast, greater freedom at home versus school and negative emotions due to social distancing were facilitators. Family/peer influence had mixed impacts. Adolescent tobacco users perceived lower COVID risks associated with HTPs and ECs than cigarettes, and various changes in tobacco use were found amid the pandemic in Hong Kong. COVID-19 and related social changes may both facilitate or deter adolescent tobacco use.


Inhibition of tracheal vascular extravasation by liposome-encapsulated albuterol in rats.
To develop a liposome-based system for systemic delivery of anti-inflammatory drugs to airways and other inflamed tissues. Postcapillary venular gap junctions open during airway inflammation and allow fluid accumulation and permit molecules (e.g. complement, kininogen) to enter tissues, initiating inflammatory cascades. Beta-adrenergic agonists prevent inflammatory plasma extravasation, but because of their deleterious side effects, they are not used intravenously. When sterically stabilized "stealth" liposomes are injected i.v., they remain in the circulation for long periods. Inflammatory mediators [e.g., substance P(SP)] open postcapillary venular gaps and allow liposomes and their contents to be deposited selectively in the inflamed tissue. We hypothesized that liposomes encapsulating a beta-adrenergic agonist, such as albuterol, would deposit selectively in inflamed airway tissue, where the drug would slowly leak out of the liposomes, resulting in closure of the gaps, thus preventing subsequent inflammatory extravasation. To test this hypothesis, we delivered albuterol-loaded liposomes i.v. in rats. Then we injected SP to open the venular gaps and allow accumulation of the drug-loaded liposomes in airway tissue. We examined whether this treatment resulted in inhibition of subsequent plasma extravasation induced by SP. The results indicate that liposome-encapsulated albuterol inhibits subsequent extravasation, presumably by leaking out of liposomes in airway tissue. This inhibition occurs for prolonged periods of time and with limited side effects compared to the effect of free albuterol. We conclude that liposomes loaded with appropriate drugs, by migrating to inflamed tissue and subsequently inhibiting inflammatory cascades, may be of therapeutic value in inflammatory diseases.


Refractive and Corneal Aberrometric Changes After Crescentic Lamellar Wedge Resection in Pellucid Marginal Degeneration.
To evaluate the effectiveness of crescentic corneal lamellar wedge resection for the treatment of pellucid marginal degeneration (PMD) in improving refractive, visual, and corneal aberrometry. The study included 10 eyes of 10 patients who had undergone corneal lamellar wedge resection for PMD. Pellucid marginal degeneration was diagnosed based on the clinical signs and corneal topography. The corneal aberrometry was evaluated with Sirius corneal topography. The mean follow-up period was 14.1 months (range, 9-24 months). Uncorrected visual acuity was improved in nine eyes and remained unchanged in 1 case, whereas best-corrected visual acuity was improved in all eyes postoperatively. By vector analysis, the overall mean astigmatic drift at the last visit was calculated to be 13.0±6.3 diopters (D). At last visit, significant reductions were found for all aberrometric measurements. However, the differences were not significant for the measurements of trefoil (P=0.189). Corneal lamellar wedge resection is a favorable surgical option for management of PMD, allowing for improved visual acuity, keratometric cylinder, and corneal aberrations.


Sexual sensation seeking and Internet sex-seeking of Middle Eastern men who have sex with men.
Despite recent evidence of stabilization in many developed nations, new human immunodeficiency virus (HIV) infections remain a public health concern globally. Efforts remain fragile in a number of world regions due to incomplete or inconsistent social policies concerning HIV, criminalization of same-sex encounters, social stigma, and religious doctrine. Middle Eastern men who have sex with men (MSM) remain one of the most hidden and stigmatized of all HIV risk groups. High-risk sexual bridging networks from these men to low prevalence populations (e.g., to spouse to offspring) are emerging HIV transmission pathways throughout the region. This cross-sectional, exploratory study investigated Sexual Sensation Seeking Scale (SSSS) scores to predict numbers of recent MSM sexual activities and to predict any recent unprotected receptive anal intercourse (URAI) activities in 86 Middle Eastern MSM who resided in the Middle East and who used the Internet to sex-seek. In a multivariate hierarchical regression, higher SSSS scores predicted higher numbers of recent MSM sexual activities (p = .028) and URAI (p = .022). In a logistic regression, higher SSSS scores increased the likelihood of engaging in URAI activities threefold (OR 3.0, 95 % CI 1.15-7.85, p = .025). Age and drug/alcohol use during sexual activities served as covariates in the regression models and were not significant in any analyses. Despite numerous hurdles, adopting Internet-based, non-restricted HIV education and prevention public health programs in the Middle East could instrumentally enhance efforts toward reducing the likelihood of new HIV transmissions in MSM and their sexual partners, ultimately contributing to an improved quality of life.


A new nanocomposite forward osmosis membrane custom-designed for treating shale gas wastewater.
Managing the wastewater discharged from oil and shale gas fields is a big challenge, because this kind of wastewater is normally polluted by high contents of both oils and salts. Conventional pressure-driven membranes experience little success for treating this wastewater because of either severe membrane fouling or incapability of desalination. In this study, we designed a new nanocomposite forward osmosis (FO) membrane for accomplishing simultaneous oil/water separation and desalination. This nanocomposite FO membrane is composed of an oil-repelling and salt-rejecting hydrogel selective layer on top of a graphene oxide (GO) nanosheets infused polymeric support layer. The hydrogel selective layer demonstrates strong underwater oleophobicity that leads to superior anti-fouling capability under various oil/water emulsions, and the infused GO in support layer can significantly mitigate internal concentration polarization (ICP) through reducing FO membrane structural parameter by as much as 20%. Compared with commercial FO membrane, this new FO membrane demonstrates more than three times higher water flux, higher removals for oil and salts (>99.9% for oil and >99.7% for multivalent ions) and significantly lower fouling tendency when investigated with simulated shale gas wastewater. These combined merits will endorse this new FO membrane with wide applications in treating highly saline and oily wastewaters.


Is attrition bias a problem in neonatal follow-up?
To assess whether attrition rate influences outcome in the follow-up of very preterm infants. In a national follow-up study of infants born alive in 1983 in the Netherlands with a gestational age less than 32 weeks and/or a birth weight less than 1500 g, outcome was assessed separately for adolescents who responded early or late to a follow-up invitation at age 14 years. Neonatal data and outcome results of earlier assessments from early and late responders were compared to those of non-responders by univariate and nominal (polytomous logistic) regression analysis. There were 723 (76%) early responders, 130 (14%) late responders and 109 (11%) non-responders. We found significantly more non-Dutch origin and more disabilities and school problems at age 10 years in late- and especially in non-responders. At age 14 years, the health utility index was significantly lower in late responders compared to early responders. School outcome did not show difference in relation to the response groups. The results suggest that the incidence of adverse outcome in very preterm infants is underestimated when follow-up is incomplete and hence response rate is not a negligible problem in the assessment of late outcome. Therefore, follow-up studies should include a drop-out analysis to enable comparison to other studies.


Improving the Ambulatory Patient Experience Within an Academic Department of Medicine.
Academic departments of medicine (ADOM) can provide an important vehicle to drive the sharing and dissemination of best practices in clinical care delivery. With the increased focus on improving the patient experience, particularly in the ambulatory setting, ADOM also should lead efforts to cultivate improvements in this arena. To address this need, the study ADOM established a Patient Experience Working Group (PEWG) that brought together physician and nonphysician leaders, set improvement goals, and created a structure for sharing and learning. Since initiation, the PEWG has implemented more than 20 performance improvement initiatives, which have resulted in measured positive changes at both the local practice settings and department-wide. Striking the right balance between top-down governance, bottom-up innovation and ownership, and shared goal setting was a key to success. This model is one that could easily be adopted by other ADOM in their own efforts to improve the patient experience.


Gray matter density of auditory association cortex relates to knowledge of sound concepts in primary progressive aphasia.
Long-term memory integrates the multimodal information acquired through perception into unified concepts, supporting object recognition, thought, and language. While some theories of human cognition have considered concepts to be abstract symbols, recent functional neuroimaging evidence has supported an alternative theory: that concepts are multimodal representations associated with the sensory and motor systems through which they are acquired. However, few studies have examined the effects of cortical lesions on the sensory and motor associations of concepts. We tested the hypothesis that individuals with disease in auditory association cortex would have difficulty processing concepts with strong sound associations (e.g., thunder). Human participants with the logopenic variant of primary progressive aphasia (lvPPA) performed a recognition task on words with strong associations in three modalities: Sound, Sight, and Manipulation. LvPPA participants had selective difficulty on Sound words relative to other modalities. Structural MRI analysis in lvPPA revealed gray matter atrophy in auditory association cortex, as defined functionally in a separate BOLD fMRI study of healthy adults. Moreover, lvPPA showed reduced gray matter density in the region of auditory association cortex that healthy participants activated when processing the same Sound words in a separate BOLD fMRI experiment. Finally, reduced gray matter density in this region in lvPPA directly correlated with impaired performance on Sound words. These findings support the hypothesis that conceptual memories are represented in the sensory and motor association cortices through which they are acquired.


Estimation of sodium and chloride storage in critically ill patients: a balance study.
Nonosmotic sodium storage has been reported in animals, healthy individuals and patients with hypertension, hyperaldosteronism and end-stage kidney disease. Sodium storage has not been studied in ICU patients, who frequently receive large amounts of sodium chloride-containing fluids. The objective of our study was to estimate sodium that cannot be accounted for by balance studies in critically ill patients. Chloride was also studied. We used multiple scenarios and assumptions for estimating sodium and chloride balances. We retrospectively analyzed patients admitted to the ICU after cardiothoracic surgery with complete fluid, sodium and chloride balance data for the first 4 days of ICU treatment. Balances were obtained from meticulously recorded data on intake and output. Missing extracellular osmotically active sodium (MES) was calculated by subtracting the expected change in plasma sodium from the observed change in plasma sodium derived from balance data. The same method was used to calculate missing chloride (MEC). To address considerable uncertainties on the estimated extracellular volume (ECV) and perspiration rate, various scenarios were used in which the size of the ECV and perspiration were varied. A total of 38 patients with 152 consecutive ICU days were analyzed. In our default scenario, we could not account for 296 ± 35 mmol of MES in the first four ICU days. The range of observed MES in the five scenarios varied from 111 ± 27 to 566 ± 41 mmol (P < 0.001). A cumulative value of 243 ± 46 mmol was calculated for MEC in the default scenario. The range of cumulative MEC was between 62 ± 27 and 471 ± 56 mmol (P = 0.001 and P = 0.003). MES minus MEC varied from 1 ± 51 to 123 ± 33 mmol in the five scenarios. Our study suggests considerable disappearance of osmotically active sodium in critically ill patients and is the first to also suggest rather similar disappearance of chloride from the extracellular space. Various scenarios for insensible water loss and estimated size for the ECV resulted in considerable MES and MEC, although these estimates showed a large variation. The mechanisms and the tissue compartments responsible for this phenomenon require further investigation.


Probiotic Lacticaseibacillus rhamnosus GG Increased Longevity and Resistance Against Foodborne Pathogens in Caenorhabditis elegans by Regulating MicroRNA miR-34.
In this study, we investigated the relation of probiotic activity of Lacticaseibacillus rhamnosus strain GG (LGG) and expression of microRNA to immune response and longevity in Caenorhabditis elegans host model. First, we evaluated the survival rate of C. elegans due to LGG exposure and bacterial colonization in the intestine. Next, the expression of mRNA and miRNA was analyzed in C. elegans exposure to LGG for 24 h using microarray. After exposure to LGG to C. elegans, colonized LGG was observed in the intestines of C. elegans and induced to extend lifespan. Moreover, persistent LGG in the intestine significantly enhanced the resistance of C. elegans exposed to both pathogenic bacteria and prolonged the lifespan of C. elegans. Transcriptome analysis indicated that LGG affected the expression levels of genes related to the innate immune response and upregulated the abundance of genes in multiple pathways of C. elegans, including Wnt signaling, TGF-beta signaling and mitogen-activated protein kinase (MAPK) pathways. In addition, qRT-PCR analysis confirmed that the expression of antibacterial genes was increased by LGG. Moreover, as the expression of microRNA miR-34 and immune-related pathways increased by exposure to LGG, the lifespan of C. elegans increased. However, in the miR-34 mutant C. elegans, the lifespan by LGG did not increase, so it was determined that miR-34 indirectly affects immune-related pathways. There was no significant difference in the expression of PMK-1 for LGG exposure in miR-34 mutants, suggesting that miR-34 may regulate PMK-1. In conclusion, we suggest that exposure of LGG to C. elegans enhances lifespan and resistance to food-borne pathogen infection by stimulating miR-34 and indirectly promoting PMK-1 activity.


An integrated infant and young child feeding and small-quantity lipid-based nutrient supplementation programme in the Democratic Republic of Congo is associated with improvements in breastfeeding and handwashing behaviours but not dietary diversity.
Integrating small-quantity lipid-based nutrient supplements (SQ-LNS) into infant and young child feeding (IYCF) programmes can increase consumption of essential nutrients among children in vulnerable populations; however, few studies have assessed the impact of integrated IYCF-SQ-LNS programmes on IYCF practices. A 2-year, enhanced IYCF intervention targeting pregnant women and infants (0-12 months) was implemented in a health zone in the Democratic Republic of Congo (DRC). The enhanced IYCF intervention included community- and facility-based counselling for mothers on handwashing, SQ-LNS, and IYCF practices, plus monthly SQ-LNS distributions for children 6-12 months; a control zone received the national IYCF programme (facility-based IYCF counselling with no SQ-LNS distributions). Cross-sectional preintervention and postintervention surveys (n = 650 and 638 in intervention and control areas at baseline; n = 654 and 653 in each area at endline, respectively) were conducted in mothers of children 6-18 months representative of both zones. Difference in differences (DiD) analyses used mixed linear regression models. There were significantly greater increases in the proportion of mothers in the intervention (vs. control) zone who reported: initiating breastfeeding within 1 hr of birth (Adj. DiD [95% CI]: +56.4% [49.3, 63.4], P < 0.001), waiting until 6 months to introduce water (+66.9% [60.6, 73.2], P < 0.001) and complementary foods (+56.4% [49.3, 63.4], P < 0.001), feeding the minimum meal frequency the previous day (+9.2% [2.7, 15.7], P = 0.005); feeding the child in a separate bowl (+9.7% [2.2, 17.2], P = 0.01); awareness of anaemia (+16.9% [10.4, 23.3], P < 0.001); owning soap (+14.9% [8.3, 21.5], P < 0.001); and washing hands after defecating and before cooking and feeding the child the previous day (+10.5% [5.8, 15.2], +12.5% [9.3, 15.6] and +15.0% [11.2, 18.8], respectively, P < 0.001 for all). The enhanced IYCF intervention in the DRC was associated with an improvement in several important IYCF practices but was not associated with a change in dietary diversity (minimum dietary diversity and minimum acceptable diet remained below 10% in both zones without significant differences between zones). The provision of fortified complementary foods, such as SQ-LNS, may be an important source of micronutrients and macronutrients for young children in areas with high rates of poverty and limited access to diverse foods. Future research should verify the potential of integrated IYCF-SQ-LNS to improve IYCF practices, and ultimately children's nutritional status.


[Sensitivity of cationic polymer Eudragit RL to electrolytes and its effect on drug release from Eudragit RL matrix].
The swelling behavior of acrylic polymer Eudragit RL in different concentration and species of electrolyte aqueous media, and the effect of media and polymer swelling on drug release from Eudragit RL matrix system were investigated with nifedipine, chlorpheniramine maleate and indomethacin as model drugs. It was found that Eudragit RL was sensitive to the electrolytes in aqueous media. The swelling of Eudragit RL decreased with increasing electrolyte concentration and was significantly affected by the electrolyte species. The swelling behavior was reversible. The release of 3 drugs from Eudragit RL matrix was remarkably affected by the electrolytes in the media. The rates of release of nifedipine and chlorpheniramine maleate from the polymer matrices were controlled by the polymer swelling behavior, and the rate of release correlated well with the swelling behavior. However, the rates of release of indomethacin from the Eudragit RL matrix were controlled not only by the polymer swelling but also by the drug displacement by the medium anion, which was attributed to the presence of an interaction between indomethacin and Eudragit RL.


The double burden of malnutrition in indigenous and nonindigenous Guatemalan populations.
As the prevalence of obesity increases in developing countries, the double burden of malnutrition (DBM) has become a public health problem, particularly in countries such as Guatemala with a high concentration of indigenous communities where the prevalence of stunting remains high. The aim was to describe and analyze the prevalence of DBM over time (1998-2008) in indigenous and nonindigenous Guatemalan populations. We used 3 National Maternal and Child Health Surveys conducted in Guatemala between 1998 and 2008 that include anthropometric data from children aged 0-60 mo and women of reproductive age (15-49 y). We assessed the prevalence of childhood stunting and both child and adult female overweight and obesity between 1998 and 2008. For the year 2008, we assessed the prevalence of DBM at the household (a stunted child and an overweight mother) and individual (stunting/short stature and overweight or anemia and overweight in the same individual) levels and compared the expected and observed prevalence rates to test if the coexistence of the DBM conditions corresponded to expected values. Between 1998 and 2008, the prevalence of childhood stunting decreased in both indigenous and nonindigenous populations, whereas overweight and obesity in women increased faster in indigenous populations than in nonindigenous populations (0.91% compared with 0.38%/y; P-trend < 0.01). In 2008, the prevalence of stunted children was 28.8 percentage points higher and of overweight women 4.6 percentage points lower in indigenous compared with nonindigenous populations (63.7% compared with 34.9% and 46.7% compared with 51.3%, respectively). DBM at the household and individual levels was higher in indigenous populations and was higher in geographic areas in which most of the population was indigenous, where there was also a greater prevalence of stunting and DBM at the individual level, both in women and children. In Guatemala, DBM is more prevalent in indigenous than in nonindigenous populations at the household and individual levels. To enhance effectiveness, current strategies of national policies and programs should consider DBM and focus on indigenous populations.


Immunocompetence of splenocytes from mice bearing different-aged tumors assessed in lymphocyte-induced angiogenesis assay.
Inbred Balb/c mice bearing 2- or 4-week-old transplantable syngeneic sarcoma L-1, when injected intravenously with the cells of the same tumor, displayed a low or high number of tumor nodules in the lungs, two weeks after the injection. In order to test whether this phenomenon is dependent on changes in host immunity associated with tumor progression, the immunocompetence of spleen cells from tumor-bearing mice was measured in a lymphocyte-induced angiogenesis assay, performed on (C57Bl/Sn X Balb/c)F1 recipients. Splenocytes from mice bearing tumors of different age, whether treated or not with cyclophosphamide, showed, however, the same angiogeneic potency.


Protein concentration in normal mouse lymphocytes, thymocytes, and mouse and human leukemic cells as measured by interference microscopy.
The apparent protein content of a single spherical lymphocyte or a similar cell, as well as its diameter, can be measured by a modified and stabilized AO-Baker interference microscope which is either fitted with an AO half-shade eyepiece or connected to a photomultiplier. This paper gives results for the apparent protein content and the diameter of normal mouse lymphocytes and thymocytes; these do not differ significantly from each other. It also gives values for the apparent protein concentration and the diameter of the lymphocytes of mice of the same strain which have developed leukemia or lymphoma; these values are significantly different from those of normal mice. Related data are given for the apparent protein content and for the diameter of normal human lymphocytes and the white cells found in myeloblastic leukemia and in stem cell leukemia in man; here the values differ significantly from those of the normal human lymphocyte. The rule seems to be that the abnormal white cells become more watery and larger as the disease advances.


Alkaline phosphatase is a predictor of Bone Mineral Density in postmenopausal females.
The study was planned to determine whether serum calcium, phosphate and alkaline phosphatase (ALP) are predictors of bone mineral density (BMD) in postmenopausal non-osteoporotic, osteopenic, and osteoporotic females. In this cross sectional study, conducted at Shaikh Zayed Hospital, Lahore in the year 2014-2015, postmenopausal females between 50-70 years of age were taken and divided into three groups non-osteoporotic (n=52), osteopenic (n=69) and osteoporotic (n=47). Serum ALP, phosphate and calcium were used in a stepwise multiple regression analysis to predict T-score in these groups. In normal postmenopausal females, the prediction model was statistically significant, F(2, 41) = 6.041, p < 0.05 and showed a T-score variance of 22%. T-score was primarily predicted by higher levels of phosphate and calcium. In postmenopausal osteopenic females, T-score was only predicted by lower levels of ALP. The model was statistically significant, F(1, 59) = 4.995, p < 0.05, and accounted for approximately 7% of the variance of T-score. In postmenopausal osteoporotic females, the prediction model contained no predictors. Our study suggested that calcium and phosphate are the strongest predictors of T-score in postmenopausal normal females, while in postmenopausal osteopenic females ALP was the strongest predictor of T-score. Elevated serum ALP levels may help in determining loss of BMD in postmenopausal females.


Efficacy and Safety of Saccharomyces boulardii in Acute Rotavirus Diarrhea: Double Blind Randomized Controlled Trial from a Developing Country.
To study the efficacy and safety of Saccharomyces boulardii (SB) in acute childhood rotavirus diarrhea. Children (3 months to 5 years) with WHO-defined acute watery diarrhea and stool rotavirus positive (n = 60) were randomized into intervention (n = 30) and control (n = 30) groups. The intervention group received SB (500 mg/day) for 5 days. The median duration (hours) of diarrhea was significantly shorter in the intervention group (60 vs. 89; 95% CI: -41.2 to - 16.8). A significantly shorter duration of hospitalization (74 vs. 91; 95% CI: -33.46 to - 0.54) was also seen in the intervention group, but no significant difference was seen for fever and vomiting. There was also no difference between the two groups in the proportion of children requiring parenteral rehydration and persistence of diarrhea lasting beyond day 7. There was no report of any adverse events. The present trial showed that SB is effective and safe in acute rotavirus diarrhea.


Parasitic infections, malnutrition and anemia among preschool children living in rural areas of Peshawar, Pakistan.
it has previously been shown that parasitic infections (PI) have deleterious effects on the nutritional status of the host, particularly among young children. the objective of this study was to estimate the severity of the problem of malnutrition and anemia in association with PI in preschool children and to identify the possible risk factors that contribute to these health problems. four hundred and thirty-seven mother-child pairs were randomly selected from rural areas of Peshawar, Pakistan. Children with visible and invisible worms were identified. The nutritional status of the respondents was evaluated. Structured questionnaires were used to collect data on relevant parameters. Appropriate statistical tests were used to analyze the data. the average age of the children was 24 ± 10 months. A total of 120 (27.5%) fecal samples of children tested positive for several parasites. Of the total, 267 (61%), 205 (47%), 109 (25%) and 140 (32%) children were anemic, stunted, wasted and underweight, respectively. The majority of wasted children (59% wasted versus 41% normal) and anemic (66% anemic versus 34% non-anemic) were infected with parasites (p < 0.05). Independent factors related to child anemia included child age, family size, mothers' awareness of overall child healthcare, and PIs. PIs were independent risk factors for malnutrition and general child wasting. Sociodemographic, parental and child-related risk factors for PIs included mothers' poor nutritional status and awareness level regarding overall child healthcare, fathers' formal education, child's pica habit, child's age, open sewage system in the houses and family size. in general, malnutrition and anemia were highly prevalent in children in association with PI.


Effects of nicotinic antagonists on working memory performance in young rhesus monkeys.
Acetylcholine plays a pivotal neuromodulatory role in the brain, influencing neuronal activity and cognitive function. Nicotinic receptors, particularly α7 and α4β2 receptors, modulate firing of dorsolateral prefrontal (dlPFC) excitatory networks that underlie successful working memory function. Minimal work however has been done examining working memory following systemic blockade of nicotinic receptor systems in nonhuman primates, limiting the ability to explore interactions of other neuromodulatory influences with working memory impairment caused by nicotinic antagonism. In this study, we investigated working memory performance after administering three nicotinic antagonists, mecamylamine, methyllycaconitine, and dihydro-β-erythroidine, in rhesus macaques tested in a spatial delayed response task. Surprisingly, we found that no nicotinic antagonist significantly impaired delayed response performance compared to vehicle. In contrast, the muscarinic antagonist scopolamine reliably impaired delayed response performance in all monkeys tested. These findings suggest there are some limitations on using systemic nicotinic antagonists to probe the involvement of nicotinic receptors in aspects of dlPFC-dependent working memory function, necessitating alternative strategies to understand the role of this system in cognitive deficits seen in aging and neurodegenerative disease.


The Role of Co-Activation and Ligand Functionalization in Neutral Methallyl Nickel(II) Catalysts for Ethylene Oligomerization and Polymerization.
A detailed quantum chemical study that analyzed the mechanism of ethylene oligomerization and polymerization by means of a family of four neutral methallyl NiII catalysts is presented. The role of the boron co-activators, BF3 and B(C6 F5 )3 , and the position of ligand functionalization (ortho or para position of the N-arylcyano moiety of the catalysts) were investigated to explain the chain length of the obtained polymers. The chain initialization proceeded with higher activation barriers for the ortho-functionalized complexes (≈19 kcal mol-1 ) than the para-substituted isomers (17-18 kcal mol-1 ). Two main pathways were revealed for the chain propagation: The first pathway was favored when using the B(C6 F5 )3 co-activated catalyst, and it produced long-chain polymers. A second pathway led to the β-hydrogen complexes, which resulted in chain oligomerization; this pathway was preferred when the BF3 co-activated catalysts were used. Otherwise, the termination of longer chains occurred via a stable hydride intermediate, which was formed with an energy barrier of about 14 kcal mol-1 for the B(C6 F5 )3 co-activated catalysts. Significant new insights were made into the reaction mechanism, whereby neutral methallyl NiII catalysts act in oligomerization and polymerization processes. Specifically, the role of co-activation and ligand functionalization, which are key information for the further design of related catalysts, were revealed.


Protection against systemic poisoning by mustard gas, di(2-chloroethyl) sulphide, by sodium thiosulphate and thiocit in the albino rat.
The lethal effects of mustard gas, di(2-chloroethyl) sulphide, in the albino rat have been counteracted by Thiocit, a mixture of sodium thiosulphate and trisodium citrate in the ratio 10:1, administered intraperitoneally in a dose of 2.75 g./kg. Thiocit afforded complete protection against greater than the median lethal dose of mustard gas whether given 10 min. before or 10 min. after mustard gas and raised the LD50 of mustard gas by approximately three times. The protection appeared whether the total dose of Thiocit was given in one injection or serially over 30 min. The effective doses of sodium thiosulphate and of Thiocit in rats were of the order of 3.0 g./kg. Sodium thiosulphate alone and Thiocit have been administered in single doses by slow infusion, by stomach tube and in drinking water. Both have shown activity by all routes of administration, but activity was greatest by intraperitoneal injection. The use of Thiocit in conjunction with mustard gas therapy is suggested.


A two-photon fluorescent probe for colorimetric and ratiometric monitoring of mercury in live cells and tissues.
Owing to the extreme toxicity of mercury, methods for its selective and sensitive sensing in solutions, and in live cells and tissues are in great demand. In this study, we developed a naphthalimide-based diphenylphosphinothioyl group-containing fluorescent and colorimetric probe that selectively detects mercury (Hg2+). Upon addition of mercury (Hg2+) to a solution of the probe, both a colorimetric change from colorless to yellow and a fluorescence change from blue to green (under a 365 nm hand-held UV lamp) occur, both of which can be observed using the "naked-eye". Furthermore, the probe possesses the capability of sensing intracellular mercury in both live cells and tissues using dual-emission channels and two-photon microscopy.


Radiologist age and diagnostic errors.
Previous investigations into the causes of error by radiologists have addressed work schedule, volume, shift length, and sub-specialization. Studies regarding possible associations between radiologist errors and radiologist age and timing of residency training are lacking in the literature, to our knowledge. The aim of our study was to determine if radiologist age and residency graduation date is associated with diagnostic errors. Our retrospective analysis included 1.9 million preliminary interpretations (out of a total of 5.2 million preliminary and final interpretations) of imaging examinations by 361 radiologists in a US-based national teleradiology practice between 1/1/2019 and 1/1/2020. Quality assurance data regarding the number of radiologist errors was generated through client facility feedback to the teleradiology practice. With input from both the client radiologist and the teleradiologist, the final determination of the presence, absence, and severity of a teleradiologist error was determined by the quality assurance committee of radiologists within the teleradiology company using standardized criteria. Excluded were 3.2 million final examination interpretations and 93,963 (1.8%) of total examinations from facilities reporting less than one discrepancy in examination interpretation in 2019. Logistic regression with covariates radiologist age and residency graduation date was performed for calculation of relative risk of overall error rates and by major imaging modality. Major errors were separated from minor errors as those with a greater likelihood of affecting patient care. Logistic regression with covariates radiologist age, residency graduation date, and log total examinations interpreted was used to calculate odds of making a major error to that of making a minor error. Mean age of the 361 radiologists was 51.1 years, with a mean residency graduation date of 2001. Mean error rate for all examinations was 0.5%. Radiologist age at any residency graduation date was positively associated with major errors (p < 0.05), with a relative risk 1.021 for each 1-year increase in age and relative risk 1.235 for each decade as well as for minor errors (p < 0.05, relative risk 1.007 for each year, relative risk 1.082 for each decade). By major imaging modality, radiologist age at any residency graduation date was positively associated with computed tomography (CT) and X-ray (XR) major and minor error, magnetic resonance imaging (MRI) major error, and ultrasound (US) minor error (p < 0.05). Radiologist age was positively associated with odds of making a major vs. minor error (p < 0.05). The mean error rate for all radiologists was low. We observed that increasing age at any residency graduation date was associated with increasing relative risk of major and minor errors as well as increasing odds of a major vs. minor error among providers. Further study is needed to corroborate these results, determine clinical relevance, and highlight strategies to address these findings.


N-glycolylneuraminic acid serum biomarker levels are elevated in breast cancer patients at all stages of disease.
Normal human tissues do not express glycans terminating with the sialic acid N-glycolylneuraminic acid (Neu5Gc), yet Neu5Gc-containing glycans have been consistently found in human tumor tissues, cells and secretions and have been proposed as a cancer biomarker. We engineered a Neu5Gc-specific lectin called SubB2M, and previously reported elevated Neu5Gc biomarkers in serum from ovarian cancer patients using a Surface Plasmon Resonance (SPR)-based assay. Here we report an optimized SubB2M SPR-based assay and use this new assay to analyse sera from breast cancer patients for Neu5Gc levels. To enhance specificity of our SPR-based assay, we included a non-sialic acid binding version of SubB, SubBA12, to control for any non-specific binding to SubB2M, which improved discrimination of cancer-free controls from early-stage ovarian cancer. We analysed 96 serum samples from breast cancer patients at all stages of disease compared to 22 cancer-free controls using our optimized SubB2M-A12-SPR assay. We also analysed a collection of serum samples collected at 6 monthly intervals from breast cancer patients at high risk for disease recurrence or spread. Analysis of sera from breast cancer cases revealed significantly elevated levels of Neu5Gc biomarkers at all stages of breast cancer. We show that Neu5Gc serum biomarker levels can discriminate breast cancer patients from cancer-free individuals with 98.96% sensitivity and 100% specificity. Analysis of serum collected prospectively, post-diagnosis, from breast cancer patients at high risk for disease recurrence showed a trend for a decrease in Neu5Gc levels immediately following treatment for those in remission. Neu5Gc serum biomarkers are a promising new tool for early detection and disease monitoring for breast cancer that may complement current imaging- and biopsy-based approaches.


[Therapy of tumor pain].
The incidence of cancer pain is about 90%. The first step in the treatment strategy is a causal therapy, including tumor mass reduction. An adequate pain management should start sometimes before the onset of a causal treatment. A good pain relief in cancer patients is mostly possible by the consequent application of the World Health Organisation 3 step analgesic ladder for the treatment of cancer. Pain management has become more comfortable since the development of new ways of applications e.g. transdermal fentanyl, water soluble morphine granulate and retarded drugs. With those new preparations, we got new possibilities and a bigger variety in the practical use of the WHO analgesic ladder. Basics for a good social integration of the patient are treatment of side effects, periodic consultations and a professional psychological support.


Effects of clonidine on diuretic response in ascitic patients with cirrhosis and activation of sympathetic nervous system.
The effects of the addition of clonidine to diuretics on the mobilization of ascites in the short term (diuretic response and requirement of diuretics) and the long term (readmissions for tense ascites and requirement of diuretics) were examined in patients with cirrhosis and with increased sympathetic nervous system (SNS) activity. We also studied neurohormonal, hemodynamic effects and side effects of clonidine and diuretics. Patients were randomized to receive placebo (group 1, n = 32) or clonidine (0.075 mg) twice daily (group 2, n = 32) for 3 months. After 8 days and for 10 days duration, spironolactone (200 mg/day) was added in both groups. After this period, the dosages of diuretics were individually increased until diuretic response. Responding patients were discharged and followed at the outpatient clinic. During the first hospitalization, the time needed for diuretic response was shorter in group 2 than in group 1. The mean requirement for diuretics was significantly higher in group 1 than in group 2, and the diuretic complications (hyperkalemia and renal impairment) were significantly lower in group 2. Clonidine induced a permanent decrease in SNS activity and delayed decrease in renin/aldosterone levels. During the follow-up, the time to the first readmission for tense ascites was shorter in group 1 than in group 2. Readmissions related to tense ascites or diuretic complications were significantly lower in group 2. The mean requirement for diuretics was significantly higher in group 1 than in group 2. In conclusion, the additional administration of clonidine to diuretics induced an earlier diuretic response associated with fewer diuretic requirements and complications.


[Total aortic arch replacement for ruptured aortic arch aneurysm in a 93-year-old woman].
Semi-emergency total aortic arch replacement was performed in a 93-year-old woman with rupture of a true saccular aneurysm at the distal aortic arch. The patient had lived by herself before surgery. She was successfully treated and showed no post-operative cerebral complications. Total aortic arch replacement must be carefully planned, because this surgery is highly invasive and is associated with a high rate of complications. This surgery is sometimes inevitably performed as a life-saving procedure in very old patients. The surgical outcome however, is less favorable. Although we used the "Eaves" technique during surgery to decrease post-operative bleeding, the surgical invasiveness itself was not reduced. Further effort is needed to develop innovative procedures.


[Feedback on Cognitive Remediation Therapy from Adolescents with Anorexia Nervosa - A Qualitative Study].
Cognitive remediation therapy (CRT) is a relatively new therapy for patients with anorexia nervosa (AN). There is an increased demand to include the patient view during the evaluation of treatment programs. So far, there is no structured evaluation of the subjective view of adolescents with AN on CRT available. 20 patients with AN between the ages of 12 and 18 years completed 10 CRT sessions. 19 patients (age: 15.6±1.3; BMI-percentile: 2.4±3.5) filled out a feedback questionnaire on their subjective CRT experience. The positive and negative aspects of CRT from a patient's perspective were inducted from the feedback material using the 'Qualitative content analysis' from Mayring, allowing the data to be summarized into different categories. The software program MAXQDA 11 was used for the data analysis. The final category system consisted of 6 general categories, which in turn were summarized into 4 main categories: "general therapy perception", "content specific therapy perception", "relationship to everyday life" and "relationship with CRT therapist". 10 patients described CRT (53%) as 'fun'. 12 patients (63%) noticed positive changes in their everyday lives, which they attributed to their participation in CRT. 4 patients (21%) were not able to notice any changes in their everyday lives. 3 patients (16%) valued the good atmosphere during the CRT sessions and 6 patients (32%) found CRT to be a welcome distraction from their daily lives on the ward. 5 patients (26%) mentioned that CRT was too demanding and that difficulties arose during their reflection on thinking styles. Overall, CRT is evaluated positively by adolescent patients with AN. A small number of patients reports difficulties with CRT and experiences CRT as strenuous. This positive evaluation of CRT is in line with results from the few qualitative studies in adults with AN. Due to a potential social desirability bias, the patient's perspective should be interpreted with slight caution. CRT is received well by adolescents with AN and poses an interesting, new therapy module in the eating disorder field.


A GPX4-targeted photosensitizer to reverse hypoxia-induced inhibition of ferroptosis for non-small cell lung cancer therapy.
Ferroptosis therapy is gradually becoming a new strategy for the treatment of non-small cell lung cancer (NSCLC) because of its active iron metabolism. Because the hypoxic microenvironment in NSCLC inhibits ferroptosis heavily, the therapeutic effect of some ferroptosis inducers is severely limited. To address this issue, this work describes a promising photosensitizer ENBS-ML210 and its application against hypoxia of NSCLC treatment based on type I photodynamic therapy and glutathione peroxidase 4 (GPX4)-targeted ferroptosis. ENBS-ML210 can promote lipid peroxidation and reduce GPX4 expression by generating superoxide anion radicals under 660 nm light irradiation, which reverses the hypoxia-induced resistance of ferroptosis and effectively kills H1299 tumor cells. Finally, the excellent synergistic antitumor effects are confirmed both in vitro and in vivo. We firmly believe that this method will provide a new direction for the clinical treatment of NSCLC in the future.


White matter hyperintensity burden on magnetic resonance imaging in essential tremor.
Whereas structural abnormalities in the cerebellum have been associated with essential tremor (ET), the contribution of vascular disease via white matter hyperintensities (WMHs) and strokes has not been examined. In this study, we have explored these potential associations and hypothesized that ET would be associated with greater overall WMH volume, greater cerebellar WMH volume, and greater infarct presence. In a cross-sectional magnetic resonance imaging (MRI) study of 540 community-dwelling elderly persons in northern Manhattan, New York, brain measures of total WMH volume and regional WMH volume were derived from T(2)-weighted fluid attenuated inverse recovery-weighted MR images. The presence of cerebral infarcts on MRI was determined as well. Total WMH volume was greater among 33 ET cases than 507 controls in both univariate (OR = 1.41, p = 0.038) and fully adjusted analyses (OR = 1.44, p = 0.03). Cerebellar WMH volume was associated with marginally increased odds of ET in a univariate model (OR = 1.52, p = 0.11) and significantly increased odds in a fully adjusted multivariate model (OR = 1.74, p = 0.049). Temporal lobe WMH volume was associated with significantly increased odds of ET in both univariate (OR = 3.36, p<0.001) and fully adjusted models (OR = 3.73, p<0.001). Large strokes were significantly more common in cases than in controls in unadjusted analyses (OR = 3.04, p = 0.02) and marginally in adjusted analyses (OR = 2.56-2.57, p = 0.045-0.056). The distribution of strokes did not differ by diagnosis. MRI data in this study indicated that ET was associated with greater total WMH volume, greater cerebellar WMH volume and possibly more strokes. Cerebrovascular disease could play a role in the development of ET.


Effects of 4 Statins on Regression of Coronary Plaque in Acute Coronary Syndrome.
There is no information on differences in the effects of moderate- and low-intensity statins on coronary plaque in patients with acute coronary syndrome (ACS). The aim of this study was to compare the effects of 4 different statins in patients with ACS, using intravascular ultrasound (IVUS). A total of 118 patients with ACS who underwent IVUS before percutaneous coronary intervention and who were found to have mild to moderate non-culprit coronary plaques were randomly assigned to receive either 20 mg/day atorvastatin or 4 mg/day pitavastatin (moderate-intensity statin therapy), or 10 mg/day pravastatin or 30 mg/day fluvastatin (low-intensity statin therapy). IVUS at baseline and at end of 10-month treatment was available in 102 patients. Mean percentage change in plaque volume (PV) was -11.1±12.8%, -8.1±16.9%, 0.4±16.0%, and 3.1±20.0% in the atorvastatin, pitavastatin, pravastatin, and fluvastatin groups, respectively (P=0.007, ANOVA). Moderate-intensity statin therapy induced regression of PV, whereas low-intensity statin therapy produced insignificant progression (-9.6% vs. 1.8%, P<0.001). On multivariate linear regression analysis, moderate-intensity statin therapy (P=0.02) and uric acid at baseline (P=0.02) were significant determinants of large percent PV reduction. LDL-C at follow-up did not correlate with percent PV change. Moderate-intensity statin therapy induced regression of coronary PV, whereas low-intensity statin therapy resulted in slight progression of coronary PV in patients with ACS. (Circ J 2016; 80: 1634-1643).


Using patient flow simulation to improve access at a multidisciplinary sleep centre.
The lack of timely access to diagnosis and treatment for sleep disorders is well described, but little attention has been paid to understanding how multiple system constraints contribute to long waiting times. The objectives of this study were to identify system constraints leading to long waiting times at a multidisciplinary sleep centre, and to use patient flow simulation modelling to test solutions that could improve access. Discrete-event simulation models of patient flow were constructed using historical data from 150 patients referred to the sleep centre, and used to both examine reasons for access delays and to test alternative system configurations that were predicted by administrators to reduce waiting times. Four possible solutions were modelled and compared with baseline, including addition of capacity to different areas at the sleep centre and elimination of prioritization by urgency. Within the model, adding physician capacity improved time from patient referral to initial physician appointment, but worsened time from polysomnography requisition to test completion, and had no effect on time from patient referral to treatment initiation. Adding respiratory therapist did not improve model performance compared with baseline. Eliminating triage prioritization worsened time to physician assessment and treatment initiation for urgent patients without improving waiting times overall. This study demonstrates that discrete-event simulation can identify multiple constraints in access-limited healthcare systems and allow suggested solutions to be tested before implementation. The model of this sleep centre predicted that investments in capacity expansion proposed by administrators would not reduce the time to a clinically meaningful patient outcome.


TailTimer: A device for automating data collection in the rodent tail immersion assay.
The tail immersion assay is a widely used method for measuring acute thermal pain in a way which is quantifiable and reproducible. It is non-invasive and measures response to a stimulus that may be encountered by an animal in its natural environment. However, quantification of tail withdrawal latency relies on manual timing of tail flick using a stopwatch, and precise temperatures of the water at the time of measurement are most often not recorded. These two factors greatly reduce the reproducibility of tail immersion assay data and likely contribute to some of the discrepancies present among relevant literature. We designed a device, TailTimer, which uses a Raspberry Pi single-board computer, a digital temperature sensor, and two electrical wires, to automatically record tail withdrawal latency and water temperature. We programmed TailTimer to continuously display and record water temperature and to only permit the assay to be conducted when the water is within ± 0.25°C of the target temperature. Our software also records the identification of the animals using a radio frequency identification (RFID) system. We further adapted the RFID system to recognize several specific keys as user interface commands, allowing TailTimer to be operated via RFID fobs for increased usability. Data recorded using the TailTimer device showed a negative linear relationship between tail withdrawal latency and water temperature when tested between 47-50°C. We also observed a previously unreported, yet profound, effect of water mixing speed on latency. In one experiment using TailTimer, we observed significantly longer latencies following administration of oral oxycodone versus a distilled water control when measured after 15 mins or 1 h, but not after 4 h. TailTimer also detected significant strain differences in baseline latency. These findings valorize TailTimer in its sensitivity and reliability for measuring thermal pain thresholds.


Remodeling the tumor microenvironment to overcome treatment resistance in HPV-negative head and neck cancer.
Despite intensive efforts and refined techniques, overall survival in HPV-negative head and neck cancer remains poor. Robust immune priming is required to elicit a strong and durable antitumor immune response in immunologically cold and excluded tumors like HPV-negative head and neck cancer. This review highlights how the tumor microenvironment could be affected by different immune and stromal cell types, weighs the need to integrate metabolic regulation of the tumor microenvironment into cancer treatment strategies and summarizes the emerging clinical applicability of personalized immunotherapeutic strategies in HPV-negative head and neck cancer.


Cardiocirculatory, hormonal, and metabolic reactions to various forms of ergometric tests.
The sympathoadrenergic reaction is not only dependent on the duration and intensity of work but also on the body position and the involvement of small or large muscle masses. This observation made in field tests comparing different sports disciplines such as swimming, running, or diving encouraged us to investigate this topic under the following laboratory conditions. Twelve healthy sport students participated in ergometric tests on a bicycle ergometer in a horizontal and vertical body position as well as on a treadmill and a swim bench ergometer. The changes of plasma catecholamines (CA) obtained in the different ergometric tests were compared with those cardiocirculatory, metabolic, and hormonal parameters which can be influenced by the sympathoadrenergic stimulation. In the horizontal body position we found a smaller increase of norepinephrine at submaximal and maximal work loads combined with a similar reaction of renin, whereas the diastolic blood pressure and the mean arterial blood pressure increased more. The substrates of lipolysis and aerobic and anaerobic glycolysis did not show obvious differences depending on the body position. In the swim bench test, however, the lactate increase started earlier and was comparatively higher than in the other ergometric tests in which the maximal work load and VO2max were higher. Although a smaller muscle mass was used and a lower maximal oxygen uptake was reached, we did not find statistically different CA values during the swim bench ergometric test compared with the bicycle ergometric test in a horizontal body position. In our ergometric tests, the venous CA levels (especially norepinephrine) were predominantly influenced by the body position.


Neuroprotective delivery platforms as an adjunct to mechanical thrombectomy.
Despite the success of numerous neuroprotective strategies in animal and preclinical stroke models, none have effectively translated to clinical medicine. A multitude of influences are likely responsible. Two such factors are inefficient recanalization strategies for large vessel occlusions and suboptimal delivery methods/platforms for neuroprotective agents. The recent endovascular stroke trials have established a new paradigm for large vessel stroke treatment. The associated advent of advanced mechanical revascularization devices and new stroke technologies help address each of these existing gaps. A strategy combining effective endovascular revascularization with administration of neuroprotective therapies is now practical and could have additive, if not synergistic, effects. This review outlines past and current neuroprotective strategies assessed in acute stroke trials. The discussion focuses on delivery platforms and their potential applicability to endovascular stoke treatment.


Decreased platelet activation and endothelial dysfunction after percutaneous mitral balloon valvuloplasty.
This study was conducted to assess the changes in platelet activation and endothelial dysfunction in patients with mitral stenosis (MS) and sinus rhythm (SR) following percutaneous mitral balloon valvuloplasty (PMBV). Systemic thromboembolism is a serious complication in patients with valvular heart disease, and its incidence is highest in those with mitral stenosis. A hypercoagulable state has also been reported in patients with mitral stenosis and sinus rhythm. A recent study has shown that patients with previous PMBV had a lower incidence of thromboembolism. The study was conducted in 21 patients (two men, 19 women, mean age=34+/-6 years) with mitral stenosis and sinus rhythm (SR) who underwent percutaneous mitral balloon valvuloplasty and 17 healthy control subjects (two men, 15 women, mean age=33+/-6 years). Biochemical markers of platelet activity (beta thromboglobulin, BTG, and soluble P-selectin, sPsel) and endothelial dysfunction (von Willebrand Factor, vWF) were measured in both control subjects' and patients' serum samples taken immediately before PMBV and 24 h after PMBV procedure. All patients underwent successful PMBV. Significant improvement of mitral valve area, pulmonary artery pressure, mean mitral gradients, and left atrial diameter were achieved in all patients after PMBV. Compared with control subjects, patients with MS had higher plasma levels of BTG (66+/-26 ng/ml vs. 14+/-6 ng/ml, P<0.001), vWF (177+/-67 units/dl vs. 99+/-37 units/dl, P<0.0001), sPsel (226+/-74 ng/ml vs. 155+/-66 ng/ml, P<0.001). There was a significant reduction of plasma levels of BTG (66+/-26 ng/ml vs. 48+/-20 ng/ml, P=0.002), vWF (177+/-67 units/dl vs. 134+/-60 units/dl, P=0.001) and P-selectin (226+/-74 ng/ml vs. 173+/-71 ng/ml, P=0.008,) 24 h after PMBV. We have shown that patients with severe MS and SR have increased platelet activation and endothelial dysfunction compared with control subjects and PMBV results in decreased platelet activity and improvement of endothelial injury.


Isolation of mitochondria from ascites tumor cells permeabilized with digitonin.
A new, improved procedure for isolating mitochondria from ascites tumor cells is described. The unique feature of this technique is the use of digitonin to make the cells susceptible to disruption by Teflon pestle/glass vessel homogenization. The yield and respiratory control ratios of mitochondria isolated by this method from murine Ehrlich ascites tumor cells and rat AS30-D ascites hepatoma cells are significantly better than those obtained for mitochondria isolated by the commonly employed Nagarse method, which involves the use of proteolytic enzymes. Moreover, mitochondria isolated by this new procedure from three different lines of tumors exhibit respiratory control ratios with both adenosine diphosphate and a respiratory uncoupler comparable to those obtained with mitochondria present in situ within digitonin-permeabilized tumor cells.


B.1.617.2 (Delta) Variant of SARS-CoV-2: features, transmission and potential strategies.
Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic. With the continuous evolution of the viral genome, SARS-CoV-2 has evolved many variants. B.1.617.2, also called Delta, is one of the most concerned variants. The Delta variant was first reported in India at the end of 2020 but has spread globally, by now, to 135 countries and is not stand still. Delta shared some mutations with other variants, and owned its special mutations on spike proteins, which may be responsible for its strong transmission and increasing virulence. Under these circumstances, a systematic summary of Delta is necessary. This review will focus on the Delta variant. We will describe all the characteristics of Delta (including biological features and clinical characteristics), analyze potential reasons for its strong transmission, and provide potential protective ways for combating Delta.


Fine needle aspiration biopsy of recurrent and metastatic osteosarcoma.
To assess the utility of fine needle aspiration (FNA) biopsy in evaluating local recurrence or disseminated metastases in patients with osteosarcoma. Cytology files from Saint Louis University Hospital and Indiana University Medical Center were searched for patients with osteosarcoma who had undergone FNA biopsy for evaluation of local recurrence or disseminated metastases. Clinical information was collected and all aspirate smears reviewed. Six FNA biopsies in five patients were procured by either the percutaneous or radiologically guided method. All six aspirates were diagnostic. Cytologic features showed a discohesive, cellular neoplasm with intermediate to large cells and oval to spindle nuclei. Chromatin was coarsely granular, with single or multiple nucleoli. Aspirate material included multinucleated giant cells and a variable amount of "osteoidlike" extracellular matrix. FNA biopsy is accurate, and these results reflect its ability to diagnose osteosarcoma when there is local recurrence or widely disseminated metastases.


Family engagement as part of managing patients with mental illness in primary care.
The family unit plays a crucial role in patients with mental illness. Mental health problems have been associated with an assortment of dysfunctional social and psychological processes in one's family of origin, yet families are now expected to be responsible for the care of the patient with mental illness. There are many short- and long-term benefits of engaging the families in the care of patients with mental illness. However, the implementation of family engagement in patients with mental illness is fraught with challenges. The primary care provider possesses several distinctive characteristics that lend an advantage to successfully engaging the families of patients with mental illness, such as better accessibility, better rapport, and being associated with less stigma. Primary care providers could engage the family in various ways, ranging from basic functions such as psychoeducation and supporting the family's needs, to more specialised interventions such as family assessment and family therapy.


A note on the temperature tolerance of Legionella.
A strain of Legionella pneumophila serogroup 1 isolated from the environment had a decimal reduction time in water at 50 degrees C (D50) of 111 min, a D54 of 27 min and a D58 of 6 min. There was little loss of viability at 46 degrees C. Other environmental organisms, a Pseudomonas sp., a Micrococcus sp. and a coliform survived less well at these temperatures. A species of Sarcina had a survival time greater than the L. pneumophila at all the temperatures tested. Other strains of legionellas were tested at 50 degrees C and decimal reduction times calculated. These ranged from 80 min for another strain of L. pneumophia serogroup 1 to 216 min for L. bozemannii . Legionella micdadei did not survive well at 50 degrees C.


Nanopattern formation in self-assembled monolayers of thiol-capped Au nanocrystals.
The structure and the stability of the transferred monolayers of gold-thiol nanoparticles, formed at air-water interface at different surface pressure, on to silicon surface have been studied using two complementary techniques, x-ray reflectivity and atomic force microscopy (AFM). Networklike nanopatterns, observed through AFM, of the in-plane aggregated nanoparticles can be attributed to the late stage drying of the liquid trapped in the islands formed by nanoparticles. During drying process the trapped liquid leaves pinholes in the islands which by the process of nucleation and growth carry the mobile nanoparticles on their advancing fronts such that the nanoparticles are trapped at the boundaries of similar adjacent holes. This process continues bringing about in-plane as well as out-of-plane restructuring in the monolayer until the liquid evaporates completely rendering a patterned structure to the islands and instability in the monolayer is then stabilized.


ERCC6L promotes cell growth and metastasis in gastric cancer through activating NF-κB signaling.
ERCC6L has been reported to act as a potential oncogenic protein in various cancers. However, the role of ERCC6L in the progression of gastric cancer (GC) remains to be elucidated. Herein, we aimed to assess the clinical significance, the role, and the underlying mechanism of ERCC6L in GC progression. In this study, the mRNA and protein expression levels of ERCC6L were measured in GC specimens by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry, and its clinical significance was assessed. The effect of ERCC6L overexpression or knockdown on GC cell growth, migration, and invasion was explored by functional experiments. Notably, the possible mechanisms underlying the action of ERCC6L were also investigated. We found that ERCC6L was upregulated in GC tissues, and its expression was associated with tumor size, clinical stage, and poor prognosis in GC patients. Besides, ERCC6L facilitated GC cell proliferation and metastasis in vitro and in vivo. Mechanically, ERCC6L modulated GC cell behavior via activation of NF-κB signaling. Our results indicated that ERCC6L played a critical role in GC progression and metastasis. In addition, ERCC6L promoted GC cell growth and metastasis via activation of NF-κB signaling, thus possibly providing a target for GC.


[Sanitary reform in the British army: introducing knowledge about practical healthcare].
This paper focuses on the development of healthcare and health instruction in the British army in the late nineteenth to twentieth centuries. Knowledge of health, nutrition and cooking could be just as important for men as for women, even though men did not have so many opportunities to know about these things in civilian life. In fact, the greatest chance for men to learn about healthcare was in military service. Its necessity, especially regarding personal care, was acknowledged at the time of the Crimean war, although it took a long time to put improvements into practice. Cookery developed as an effective way to deliver practical knowledge about health to soldiers; indeed, cooking and healthcare instruction became a part ofArmy regulations and medical officers expected that the instruction given would translate into useful common sense for later life. Cookery education started as training for hospital cooks; later it extended to individual cooking for troops in the field. For many young men, therefore, joining the armed forces provided a unique opportunity to alter their unhealthy life style, not only for the sake of the Army but for their own benefit and that of society at large.


Myocardial scintigraphy and clinical stratification as predictors of events in renal transplant candidates.
We tested the hypothesis that the universal application of myocardial scanning with single-photon emission computed tomography (SPECT) would result in better risk stratification in renal transplant candidates (RTC) compared with SPECT being restricted to patients who, in addition to renal disease, had other clinical risk factors. RTCs (n=363) underwent SPECT and clinical risk stratification according to the American Society of Transplantation (AST) algorithm and were followed up until a major adverse cardiovascular event (MACE) or death. Of the 363 patients, 79 patients (22%) had an abnormal SPECT scan and 270 (74%) were classified as high risk. Both methods correctly identified patients with increased probability of MACE. However, clinical stratification performed better (sensitivity and negative predictive value 99% and 99% vs. 25% and 87%, respectively). High-risk patients with an abnormal SPECT scan had a modest increased risk of events (log-rank = 0.03; hazard ratio [HR] = 1.37; 95% confidence interval [95% CI], 1.02-1.82). Eighty-six patients underwent coronary angiography, and coronary artery disease (CAD) was found in 60%. High-risk patients with CAD had an increased incidence of events (log-rank = 0.008; HR=3.85; 95% CI, 1.46-13.22), but in those with an abnormal SPECT scan, the incidence of events was not influenced by CAD (log-rank = 0.23). Forty-six patients died. Clinical stratification, but not SPECT, correlated with the probability of death (log-rank = 0.02; HR=3.25; 95% CI, 1.31-10.82). SPECT should be restricted to high-risk patients. Moreover, in contrast to SPECT, the AST algorithm was also useful for predicting death by any cause in RTCs and for selecting patients for invasive coronary testing.


The Preservation of Spousal and Partner Relationships Among Nursing Home Residents.
Deciding to seek placement in a nursing home can be difficult for both older adults and their families, but especially so for spouses or partners of potential nursing home residents. Disruption of the attachment relationship following placement is likely to influence the psychosocial well-being of nursing home residents. This mixed-method study explored services and activities offered that emphasize the preservation of spousal and partner relationships among nursing home residents. A survey was administered to nursing home social workers in the states of Alabama, Georgia, Mississippi, and Tennessee. Survey results reveal that approximately 49% of respondents reported having a written policy to preserve these relationships, however, only 22% reported having a program to carry out the facility's written policy. Both survey respondents and interview participants highlighted privacy and outings as ideal relationship-preserving practices. Nursing home social workers can utilize the study results in the design and implementation of specific services to preserve relationships between residents and their spouses/partners.


BRCA1 sequence variations in 160 individuals referred to a breast/ovarian family cancer clinic. Institut Curie Breast Cancer Group.
An account of familial aggregation in breast/ovarian cancer has become possible with the identification of BRCA1 germ-line mutations. We evaluated, for 249 individuals registered with the Institut Curie in Paris, the prior probability that an individual carried a mutation that predisposes to these diseases. We chose 160 women for BRCA1 analysis: 103 with a family history of breast cancer and 57 with a family history of breast-ovarian cancer. To detect small mutations, we generated and analyzed 35 overlapping genomic PCR products that cover the coding portion of the gene, by using denaturing gradient gel electrophoresis. Thirty-eight truncating mutations (32 frameshifts, 4 nonsense mutations, and 2 splice variants) were observed in 15% of women with a family history of breast cancer only and in 40% of those with a history of breast-ovarian cancer. Twelve of 25 distinct truncating mutations identified were novel and unique. Most BRCA1 mutations that had been reported more than five times in the Breast Cancer Information Core were present in our series. One mutation (5149del4) observed in two apparently unrelated families most likely originates from a common ancestor. The position of truncating mutations did not significantly affect the ratio of the risk of breast cancer to that of ovarian cancer. In addition, 15 DNA variants (14 missense mutations and 1 neutral mutation) were identified, 9 of which were novel. Indirect evidence suggests that seven of these mutations are deleterious.


Enhanced Alignment of Water-Soluble Polythiophene Using Cellulose Nanocrystals as a Liquid Crystal Template.
Cellulose nanocrystals (CNCs) are bioderived, rodlike particles that form a chiral nematic liquid crystal (LC) in water. In this work, CNCs were used to induce long-range order in a semiconducting polymer, poly[3-(potassium-4-butanoate) thiophene-2,5-diyl] (PPBT). When mixed with CNCs, it was found that PPBT was incorporated into the liquid crystal "template" to form ordered structures with highly birefringent domains, as observed under polarized light. We show that the π-π interactions between polymer chains, which contribute considerably to the energetics of the semiconducting system, are directly influenced by the presence and packing of the liquid crystal phase. Upon increasing the concentration of CNCs from the isotropic to chiral nematic regime, we observe a bathochromic shift in the UV-vis spectra and the emergence of the 0-0 vibrational peak, suggesting enhanced π-π stacking leading to chain coplanarization. Furthermore, the chiral nature of the PPBT/CNC mixture was evidenced by a negative peak in circular dichroism (CD) spectroscopy, promoting the notion that the polymer chains followed the helicoidal twist of the chiral nematic liquid crystal host. At high temperatures, the peak height ratios and overall intensities of the UV-vis and CD spectra associated with PPBT decreased as the chiral nematic pitch grew larger in size.


Membrane transport properties of equine and macaque ovarian tissues frozen in mixtures of dimethylsulfoxide and ethylene glycol.
The rate at which equine and macaque ovarian tissue sections are first cooled from +25 degrees C to +4 degrees C has a significant effect on the measured water transport when the tissues are subsequently frozen in 0.85 M solutions of glycerol, dimethylsulfoxide (DMSO), or ethylene glycol (EG). To determine whether the response of ovarian tissues is altered if they are suspended in mixtures of cryoprotective agents (CPAs), rather than in solutions of a single CPA, we have now measured the subzero water transport from ovarian tissues that were suspended in mixtures of DMSO and EG. Sections of freshly collected equine and macaque ovaries were suspended either in a mixture of 0.9 M EG plus 0.7 M DMSO (equivalent to a mixture of approximately 5% vv of EG and DMSO) or in a 1.6M solution of only DMSO or only EG. The tissue sections were cooled from +25 degrees C to +4 degrees C and then frozen to subzero temperatures at 5 degrees C/min. As the tissues were being frozen, a shape-independent differential scanning calorimeter technique was used to measure water loss from the tissues and, consequently, the best fit membrane permeability parameters (L(pg) and E(Lp)) of ovarian tissues during freezing. In the mixture of DMSO+EG, the respective values of L(pg) and E(Lp) for equine tissue first cooled at 40 degrees C/min between +25 degrees C and +4 degrees C before being frozen were 0.15 microm/min atm and 7.6 kcal/mole. The corresponding L(pg) and E(Lp) values for equine tissue suspended in 1.6M DMSO were 0.12 microm/min atm and 27.2 kcal/mole; in 1.6M EG, the values were 0.06 microm/min atm and 21.9 kcal/mole, respectively. For macaque ovarian tissues suspended in the mixture of DMSO+EG, the respective values of L(pg) and E(Lp) were 0.26 microm/min atm and 26.2 kcal/mole. Similarly, the corresponding L(Lg) and E(Lp) values for macaque tissue suspended in 1.6M DMSO were 0.22 microm/min atm and 31.4 kcal/mole; in 1.6 M EG, the values were 0.20 microm/min atm and 27.9 kcal/mole. The parameters for both equine and macaque tissue samples suspended in the DMSO+EG mixture and first cooled at 0.5 degrees C/min between +25 degrees C and +4 degrees C were very similar to the corresponding values for samples cooled at 40 degrees C/min. In contrast, the membrane parameters of equine and macaque samples first cooled at 0.5 degrees C/min in single-component solutions were significantly different from the corresponding values for samples cooled at 40 degrees C/min. These results show that the membrane properties of ovarian cells from two species are different, and that the membrane properties are significantly affected both by the solution in which the tissue is suspended and by the rate at which the tissue is cooled from +25 degrees C to +4 degrees C before being frozen. These observations suggest that these variables ought to be considered in the derivation of methods to cryopreserve ovarian tissues.


Mast cells in periapical lesions: potential role in their pathogenesis.
The aim of this study was to qualitatively and semi-quantitatively analyze mast cells in periapical lesions. Biopsy specimens of 96 periapical lesions were stained with hematoxylin-eosin, histochemical Giemsa and immunohistochemical CD 117 (C kit) antibody. Mast cell count below 100 mast cells on 1000 fields of high power magnification was noted as 'negative', 101-400 as 'mild', 401-800 cells as 'moderate', and over 800 cells as 'severe'. Mast cells are found in 68 (70.8%) lesions. The presence of mast cells was greater in cysts than in granulomas (P < 0.0028). There was no difference in semi-quantitative expression of CD 117 in granulomas and cysts (P > 0.05). Mast cells were placed in both: inflammatory infiltrate and in fibroblastic areas of periapical lesions, and their presence was most frequently mild to moderate. The findings of present study could suggest a role of mast cells in regulation of cellular immune mechanisms in periapical lesions, balancing between alterative and reparatory processes in inflamed periapical tissue.


Control of nuclear centration in the C. elegans zygote by receptor-independent Galpha signaling and myosin II.
Mitotic spindle positioning in the Caenorhabditis elegans zygote involves microtubule-dependent pulling forces applied to centrosomes. In this study, we investigate the role of actomyosin in centration, the movement of the nucleus-centrosome complex (NCC) to the cell center. We find that the rate of wild-type centration depends equally on the nonmuscle myosin II NMY-2 and the Galpha proteins GOA-1/GPA-16. In centration- defective let-99(-) mutant zygotes, GOA-1/GPA-16 and NMY-2 act abnormally to oppose centration. This suggests that LET-99 determines the direction of a force on the NCC that is promoted by Galpha signaling and actomyosin. During wild-type centration, NMY-2-GFP aggregates anterior to the NCC tend to move further anterior, suggesting that actomyosin contraction could pull the NCC. In GOA-1/GPA-16-depleted zygotes, NMY-2 aggregate displacement is reduced and largely randomized, whereas in a let-99(-) mutant, NMY-2 aggregates tend to make large posterior displacements. These results suggest that Galpha signaling and LET-99 control centration by regulating polarized actomyosin contraction.


Treatments for Acute Nonarteritic Central Retinal Artery Occlusion: Findings From a Cochrane Systematic Review.
Many interventions for nonarteritic central retinal artery occlusion (CRAO) are associated with serious complications and little effect on visual outcomes. We report on the findings of a Cochrane systematic review that searched seven databases for peer-reviewed articles reporting on treatments for acute nonarteritic CRAO. We assessed six randomized controlled trials, including interventions such as tissue plasminogen activator (t-PA), isovolumic hemodilution, eyeball massage, intraocular pressure reduction, anticoagulation, vasodilation, oxygen inhalation, laser embolysis, transcorneal electrical stimulation, thrombolysis, pentoxifylline, and enhanced external counterpulsation. However, none of the randomized controlled trials demonstrated significant improvement in visual acuity at 1 month compared to observation, and some patients treated with t-PA experienced serious adverse effects including intracranial hemorrhage. Proposed interventions for acute nonarteritic CRAO may not be better than observation, but the evidence is uncertain. Larger, well-designed studies are necessary to determine the most effective management option for acute nonarteritic CRAO. [Ophthalmic Surg Lasers Imaging Retina 2023;54:650-653.].


Involvement of adenosine A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of cocaine and methamphetamine in rats.
Adenosine, by acting on adenosine A1 and A2A receptors, is known to antagonistically modulate dopaminergic neurotransmission. We have recently reported that nonselective adenosine receptor antagonists (caffeine and 3,7-dimethyl-1-propargylxanthine) can partially substitute for the discriminative-stimulus effects of methamphetamine. In the present study, by using more selective compounds, we investigated the involvement of A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of both cocaine and methamphetamine. The effects of the A1 receptor agonist N6-cyclopentyladenosine (CPA; 0.01-0.1 mg/kg) and antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 1.3-23.7 mg/kg) and the A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680; 0.03-0.18 mg/kg) and antagonist 3-(3-hydroxypropyl)-8-(3-methoxystyryl)-7-methyl-1-propargylxanthin phosphate disodium salt (MSX-3; 1-56 mg/kg) were evaluated in rats trained to discriminate either 1 mg/kg methamphetamine or 10 mg/kg cocaine from saline under a fixed-ratio 10 schedule of food presentation. The A1 and A2A receptor antagonists (CPT and MSX-3) both produced high levels of drug-lever selection when substituted for either methamphetamine or cocaine and significantly shifted dose-response curves of both psychostimulants to the left. Unexpectedly, the A2A receptor agonist CGS 21680 also produced drug-appropriate responding (although at lower levels) when substituted for the cocaine-training stimulus, and both CGS 21680 and the A1 receptor agonist CPA significantly shifted the cocaine dose-response curve to the left. In contrast, both agonists did not produce significant levels of drug-lever selection when substituted for the methamphetamine-training stimulus and failed to shift the methamphetamine dose-response curve. Therefore, adenosine A1 and A2A receptors appear to play important but differential roles in the modulation of the discriminative-stimulus effects of methamphetamine and cocaine.


Issues with polymorphism analysis in sepsis.
Genetic variation has been shown to play a large role in determining susceptibility to and outcome of such complex diseases as sepsis. There is a much higher heritability of death due to infection than death due to cancer or heart disease. More than 8 million single nucleotide polymorphisms (SNPs) have been detected in the human genome, and there is very little understanding of their effect on gene expression and protein function. The use of haplotypes, which are inherited sets of linked SNPs, as the unit of genetic variation in association studies and the marking of these haplotypes with unique "tag SNPs" may help to narrow down the search for causal SNPs. Future studies must be large (thousands of patients) and must be carefully designed to avoid false associations resulting from ethnic differences in genotype frequencies and disease prevalence in order to find true, reproducible associations between genotype and phenotype. Functional studies and careful characterization of intermediate phenotypes must be done to lend biological plausibility to genotype-phenotype associations. Examination of the association between genetic polymorphisms and sepsis promises to provide clinicians with new tools to evaluate prognosis, to intervene early and aggressively in treating high-risk persons, and to avoid the use of therapies with adverse effects in treating low-risk persons.


Surgical Strategy for T2 Gallbladder Cancer According to Tumor Location.
Radical cholecystectomy is recommended for T2 gallbladder cancer. However, it is unclear whether hepatic resection is essential for peritoneal-side gallbladder cancer. From January 2000 to December 2011, we identified T2 gallbladder cancer patients who had undergone curative intent surgery. A peritoneal-side tumor was defined when the epicenter of the tumor was located within the free peritoneal-side gallbladder mucosa. Hepatic-side gallbladder cancer was defined when the epicenter of the tumor was located within the gallbladder bed or neck. A total of 157 patients with T2 gallbladder cancer were included; 33 peritoneal-side and 124 hepatic-side tumors. In total, 122 patients underwent hepatic resection, whereas the remaining 35 patients did not. After a median follow-up period of 40 (range 5-170) months, the survival of the peritoneal-side group was better than that of the hepatic-side group (p = 0.002). In a multivariate analysis, tumor location, lymph node metastasis, hepatic resection, lymphatic invasion, and perineural invasion were significant prognostic factors (p = 0.045, p < 0.001, p = 0.003, p = 0.046, and p = 0.027, respectively). For the peritoneal-side group, there was no recurrence or death after cholecystectomy without hepatic resection. However, hepatic resection was an important factor associated with overall survival in patients with hepatic-side gallbladder cancer (p = 0.007). In T2 gallbladder cancer patients, hepatic resection is recommended when there is tumor invasion of the gallbladder bed or neck. However, it is not always necessary in selected patients with peritoneal-side gallbladder cancer.