Weekly luteal-phase dosing with enteric-coated fluoxetine 90 mg in premenstrual dysphoric disorder: a randomized, double-blind, placebo-controlled clinical trial.
Because the symptoms of premenstrual dysphoric disorder (PMDD) are limited to the luteal phase of the menstrual cycle, the potential benefit of luteal-phase dosing has been hypothesized. This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial evaluated the efficacy and tolerability of enteric-coated fluoxetine 90 mg given once or twice during the luteal phase for the treatment of PMDD. Study drug was given 14 and 7 days before expected menses during the luteal phase of 3 menstrual cycles. After a screening period and single-blind placebo lead-in period, eligible women were randomized to I of 3 treatment groups: enteric-coated fluoxetine 90 mg on both days (LPWDx2); placebo 14 days before menses and enteric-coated fluoxetine 90 mg 7 days before menses (LPWDx1); or placebo on both days (PLC). The primary efficacy measure was change from baseline in mean luteal-phase scores on the Daily Record of Severity of Problems (DRSP). Secondary efficacy measures included scores on the Rating Scale for Premenstrual Tension Syndrome, Clinician-Rated (PMTS-C); the Clinical Global Impression (CGI)-Severity scale; and the Patient Global Impression (PGI)-Improvement scale. Quality of life was assessed using the Sheehan Disability Scale. Two hundred fifty-seven women were randomized to treatment. At the end of the study, the LPWDx2 group had statistically significant improvements in DRSP total, DRSP mood subtotal, DRSP social functioning subtotal, PMTS-C, CGI-Severity, PGI-Improvement, and Sheehan Disability Scale work and family life scores compared with LPWDx1 and PLC (each measure, P < 0.05). There was also a statistically significant improvement in the score on the social life section of the Sheehan Disability Scale with LPWDx2 compared with PLC (P = 0.037). Across all treatment groups, 5 patients discontinued due to nonserious adverse events. Rates of discontinuation for any reason did not differ between the 3 treatment groups. The findings of this study support the efficacy and tolerability of enteric-coated fluoxetine 90 mg given twice during the luteal phase of the menstrual cycle for the treatment of PMDD.


Effect of Oral Chinese Medicine Combined with Western Medicine on Cancer Pain: A Meta-Analysis.
To assess the effect of oral Chinese medicine (OCM) combined with Western medicine (WM) on cancer pain. PubMed, Embase, Cochrane Library, Clinical Trials Registry Platform, Chinese National Knowledge Infrastructure (CNKI), Wanfang and VIP databases were searched from their inception to September {dy2019}. Randomized controlled trials (RCTs) treating cancer pain by Chinese medicine (CM) combined with WM were included. The primary outcome were total pain relief rate and the quality of life (QOL), and the other outcomes were the average daily dosage of analgesics, the primary time of pain, the analgesic duration time, and adverse events. The methodological quality of RCTs was assessed in accordance with Cochrane 5.1.0 handbook of systematic reviews of interventions. Evidence level was assessed by the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. There were 1,087 patients in the 14 studies, with 544 in the experiment group and 543 in the control group. These studies were all conducted in China, and published between 2006 and {dy2019}. Compared with the WM, OCM combined with WM could significantly relieve the cancer pain [risk ratio (RR)=1.43, 95% confidence interval (CI): 1.32, 1.56), improve QOL (RR=8.57, 95% CI: 4.25, 12.89), decrease the primary time of pain (RR=-0.20, 95% CI: -0.24, -0.16], prolong the analgesic duration time (RR=3.47, 95% CI: 2.09, 4.85), reduce the dosage of analgesics (RR=-19.52, 95% CI: -36.32, -2.72), and reduce side events (RR=0.49, 95% CI: 0.37, 0.65). Evidence levels for total pain relief rate, primary time of pain and side events were low, evidence level for QOL, analgesic duration time and average daily dosage of analgesics were very low. Compared with the WM, OCM combined with WM could significantly relieve the cancer pain, improve the QOL, decrease the primary time of pain, prolong the analgesic duration time, reduce the dosage of analgesics and side events. The evidence levels were low or very low.


Quasi-stiffness of the knee joint is influenced by walking on a destabilising terrain.
Predictive models have been devised to estimate the necessary quasi-stiffness that a transfemoral prosthesis should be set to aligning the body and gait parameters of the user. Current recommendations exist only for walking over level ground. This study aimed to ascertain whether walking across destabilising terrain influences the quasi-stiffness of the knee joint thus influencing prosthetic engineering. Ten healthy males (age: 25.1 ± 2.5 years; mean ± sd, height: 1.78 ± 0.05 m, weight: 84.40 ± 11.02 kg) performed 14 gait trials. Seven trials were conducted over even ground and seven over 20 mm ballast. Three-dimensional motion capture and ground reaction force were collected. Paired samples t-tests and Wilcoxon signed ranked test compared variables including; quasi-stiffness, gait speed, stride length and stride width. Quasi-stiffness (d = 0.562, P = 0.001) and stride width (d = 0.909, P < 0.001) were significantly greater in the destabilising terrain condition. Gait speed (r = -0.731, P = 0.001) was significantly greater in the control condition. No significant difference was seen in stride length (d = 0.583, P = 0.016). An increase in quasi-stiffness when walking across destabilising terrain was attributed to a magnified shock absorption mechanism, facilitating an increased flexion angle during the stance phase. This causes a lower centre of mass resulting in the musculoskeletal system having to produce a greater knee extensor moment to prevent the knee collapsing. Therefore, transfemoral prostheses should be tuned to apply increased extension moments if ambulation is to occur on a destabilising terrain.


[Planning of sampling for linkage analysis. Sample size and sampling method].
There is a proposed method for evaluation of the minimal sample size needed for the predefined quality of the linkage decision. It is applied to samples of arbitrary structured pedigrees ascertained via proband in accordance with different ascertainment schemes. The quality of the linkage decision is determined by the I and II type errors of the likelihood ratio constructed with a simple alternative hypothesis about the recombination fraction value. Comparison of these minimal sample sizes for different ascertainment schemes leads to a possibility to choose the best of them when the model of genetic control of two traits is given. A possibility to evaluate each of these ascertainments by a cost of the sample collection and to point out the cheapest is considered.


Alginate hydrogels: A potential tissue engineering intervention for intervertebral disc degeneration.
Intervertebral disc (IVD) degeneration is a major cause of low back pain and disability, affecting millions of people worldwide. Current treatments for IVD degeneration are limited to invasive surgery or pain management. Recently, there has been increasing interest in the use of biomaterials, such as alginate hydrogels, for the treatment of IVD degeneration. Alginate hydrogels are an example of such a biomaterial that is biocompatible and can be tailored to mimic the native extracellular matrix of the IVD. Derived from alginate, a naturally derived polysaccharide from brown seaweed that can be transformed into a gelatinous solution, alginate hydrogels are emerging in the field of tissue engineering. They can be used to deliver therapeutic agents, such as growth factors or cells, to the site of injury, providing a localized and sustained release that may enhance treatment outcomes. This paper provides an overview on the use of alginate hydrogels for the treatment of IVD degeneration. We discuss the properties of alginate hydrogels and their potential applications for IVD regeneration, including the mechanism against IVD degeneration. We also highlight the research outcomes to date along with the challenges and limitations of using alginate hydrogels for IVD regeneration, including their mechanical properties, biocompatibility, and surgical compatibility. Overall, this review paper aims to provide a comprehensive overview of the current research on alginate hydrogels for IVD degeneration and to identify future directions for research in this area.


Rapamycin suppresses TLR4-triggered IL-6 and PGE(2) production of colon cancer cells by inhibiting TLR4 expression and NF-kappaB activation.
Toll-like receptor 4 (TLR4) signaling in tumor cells can mediate tumor cell immune escape and tumor progression, being regarded as one of the mechanisms for chronic inflammation in tumorigenesis and progression. So, intervention of TLR4-mediated immune escape and metastasis has been proposed as one of the approaches to cancer prevention and treatment. Rapamycin, an immunosuppressant agent widely used for treatment of autoimmune diseases and transplantation rejection, is recently used for cancer therapy. However, the underlying mechanisms remain to be fully understood. In the present study, we demonstrate that rapamycin can significantly inhibit TLR4-triggered IL-6 and PGE(2) production and invasion of colon cancer cells. Suppression of TLR4-induced IL-6 and PGE(2) production is responsible for the rapamycin-mediated decrease of TLR4-evoked invasion of colon cancer cells. Furthermore, disruption of NF-kappaB pathway contributes to the inhibition of TLR4-induced IL-6, PGE(2) production and invasion by rapamycin in colon cancer cells. Rapamycin can also downregulate TLR4 expression. Therefore, we demonstrate that rapamycin may abrogate TLR4-triggered tumor cell immune escape and invasion by downregulating TLR4 expression and inhibiting TLR4-activated NF-kappaB pathway, thus providing new mechanistic explanation for the antitumor effect of rapamycin.


Actions of bile salts and of papaverine and intracellular cyclic AMP in isolated rat uterus.
Both antioxytocin and antiphosphodiesterase activities of desoxycholate were potentiated by lowering the pH of the medium. The results suggest the possibility that it is the bile salt in the non-ionized form which exerts the antioxytocin and antiphosphodiesterase action. The concentration of tissue cyclic AMP was measured at different times during relaxation of the uterus. The results show a significant increase in tissue cyclic AMP concentration at a time when the muscle was just beginning to relax in response to papaverine, but not in response to chenodesoxycholate. The intracellular level of cyclic AMP during relaxation of the uterus produced by papaverine or chenodesoxycholate was, however, significantly increased when relaxation was about 90% complete. The difference between the mode of action of papaverine and that of the bile salts is discussed.


Electrogenic events in the ubiquinone-cytochrome b/c2 oxidoreductase of Rhodopseudomonas sphaeroides.
The reductant of ferricytochrome c2 in Rhodopseudomonas sphaeroides is a component, Z, which has an equilibrium oxidation-reduction reaction involving two electrons and two protons with a midpoint potential of 155 mV at pH 7. Under energy coupled conditions, the reduction of ferricytochrome c2 by ZH2 is obligatorily coupled to an apparently electrogenic reaction which is monitored by a red shift of the endogeneous carotenoids. Both ferricytochrome c2 reduction and the associated carotenoid bandshift are similarly affected by the concentrations of ZH2 and ferricytochrome c2, pH, temperature the inhibitors diphenylamine and antimycin, and the presence of ubiquinone. The second-order rate constant for ferricytochrome c2 reduction at pH 7.0 and at 24 degrees C was 2 - 10(9) M-1 - s-1, but this varied with pH, being 5.1 - 10(8) M-1 = s-1 at pH 5.2 and 4.3 - 10(9) M-1 - s-1 at pH 9.3. At pH 7 the reaction had an activation energy of 10.3 kcal/mol.


Role of age, sex, and specific provoking factors on the distal versus proximal presentation of first symptomatic deep vein thrombosis: analysis of the SWIss Venous ThromboEmbolism Registry (SWIVTER).
We aimed to evaluate the impact of age, sex, and their interactions with provoking risk factors for deep vein thrombosis (DVT). In addition, we intended to provide additional insights on risk factors associated with the isolated distal versus proximal presentation of first symptomatic acute DVT, both being characterized by different prognosis. In the present analysis from the SWIss Venous ThromboEmbolism Registry (SWIVTER), we compared demographic and baseline characteristics in patients with isolated distal (n = 184; 35%) versus proximal (n = 346) DVT of the lower limbs without symptomatic pulmonary embolism, and identified factors related with the presenting thrombosis location. In the overall population, mean age was 59 ± 19 years, 266 (50%) were women, 106 (20%) patients had cancer, 86 (16%) recent surgery, and 52 (10%) acute infection/sepsis. In a multivariable analysis, recent surgery [odds ratio (OR) 2.92, 95% confidence interval (CI) 1.80-4.73] was independently associated with a diagnosis of isolated distal DVT, whereas cancer (OR 2.01, 95% CI 1.20-3.35), male sex aged 41 to 75 years (OR 2.21, 95% CI 1.33-3.67), and acute infection/sepsis (OR 2.71, 95% CI 1.29-5.66) with a diagnosis of proximal DVT. In SWIVTER, age, sex, and several provoking risk factors for VTE appeared to be related with the presenting location of first symptomatic DVT. Cancer, male sex, and acute infection/sepsis were associated with a proximal location of DVT, whereas recent surgery was associated with a distal presentation, likely acting as confounders for the association between thrombosis location and prognosis.


Sport and self-esteem in people living with HIV: a cross-sectional study.
In the general population, sport activity is associated with better health and better self-esteem. Among people living with HIV (PLHIV), sport activity could also be associated with better self-esteem. The main objective of our study was to assess the association between sport activity and self-esteem among people living with HIV. The secondary objectives were to evaluate the associations between sport activity with fatigue as well as with pain. We performed a cross-sectional observational study among PLHIV in our region (Pays de la Loire in France). Each adult seen in routine HIV care was invited to participate in the study. Participants were invited to fill out self-questionnaires about sport activity, self-esteem, fatigue, and pain. The 2 groups of participants with and without sport activity were compared with a T Student test for self-esteem, fatigue, and pain scales. Among the 1160 people included in the study, 47% performed sport activity. The self-esteem score was better in the "sporting group" compared with the "non sporting group" (Rosenberg mean scale 32.7 ± 5.1/40 vs 31.9 ± 5 p = 0.01). The Functional Assessment of Chronic Illness Therapy Fatigue scale showed a lower fatigue in the sporting group than in the non-sporting group (mean total score 125 ± 22 vs 118 ± 24 p < 0.0001). The sporting group had a lower mean pain score (1.1 ± 1.8) than the non sporting group (1.4 ± 1.9 p = 0.004). Among PLHIV in our region, sport activity was associated with better self-esteem, lower fatigue and lower pain. Sport activity should be included in patient care for people living with HIV.


A short guide to studying medicine for the dental graduate.
Advice is offered to dentally-qualified trainees with an interest in oral and maxillofacial surgery who may be considering applying for a place in medical school from two trainees who have recently completed their medical studies.


Assessment, diagnosis and treatment of peristomal skin lesions by remote imaging: An expert validation study.
Prevention and treatment of peristomal skin problems should be a priority for nurses caring for ostomates, even when the assessment of lesions must be done remotely. To measure the level of agreement on assessment, diagnosis and care indications for peristomal skin lesions using remote imaging among nurses in Spain. Prospective observational multicentre study to assess the diagnostic validity and inter- and intraobserver agreement between nurses in peristomal skin lesions. Data were collected between March and October 2019. The research sample consisted of a group of 39 nurses with expertise in the care of ostomates. A panel of experts established a list of 24 common signs/findings, 15 diagnostic options and 35 treatment approaches for peristomal skin lesions. Three expert stoma therapy nurses compiled the clinical cases, which they described thoroughly and documented with photographs. The 39 participating nurses evaluated the cases in two rounds to measure inter and intraobserver agreement. A high or very high level of agreement (κ > 0.61) was observed for the following signs: encrustation, nodules, mucocutaneous separation and varicose veins; for the following diagnoses: mucocutaneous dehiscence, allergic contact dermatitis, encrustation and varicose veins (caput medusae); for the following treatments: recommending a diet rich in vitamin C/blueberries, applying acetic acid dressings, applying cold and topical tacrolimus treatment. The most easily identifiable lesions were those most prevalent and with visible signs. There was a lower level of agreement in identifying lesions for which photographs required additional information (laboratory data, description of signs and symptoms, type of diet and level of self-care). It is important to train nurses caring for ostomates to correctly describe ostomy-related lesions, which is important for nursing records, continuity of care and telehealth care.


Spherical wave scattering from rough surfaces and array processing: Application to sound-speed profile measurement uncertainty analysis.
A three-dimensional modeling of spherical wave reflection on layered media with rough interfaces is used to study the roughness influence in sediment sound-speed profile measurements. The configuration of the numerical experiment consists of a point source and a horizontal array of hydrophones. In addition, theoretical uncertainties on the angle of arrival and travel time of a spherical wave reflected over a slightly rough interface are derived by including the array processing in the Helmholtz-Kirchhoff integral. The sound-speed profile sensitivity to those parameters is used to compare theory and numerical experiments. The agreement is good and shows a surprisingly strong influence of the roughness on the sound-speed profile measurement.


Sphingosine kinase 1 is required for migration, proliferation and survival of MCF-7 human breast cancer cells.
Sphingosine-1-phosphate (S1P) is a potent lysolipid involved in a variety of biological responses important for cancer progression. Therefore, we investigated the role of sphingosine kinase type 1 (SphK1), the enzyme that makes S1P, in the motility, growth, and chemoresistance of MCF-7 breast cancer cells. Epidermal growth factor (EGF), an important growth factor for breast cancer progression, activated and translocated SphK1 to plasma membrane. SphK1 was required for EGF-directed motility. Downregulation of SphK1 in MCF-7 cells reduced EGF- and serum-stimulated growth and enhanced sensitivity to doxorubicin, a potent chemotherapeutic agent. These results suggest that SphK1 may be critical for growth, metastasis and chemoresistance of human breast cancers.


Adsorption and flocculation of bentonite by chitosan with varying degree of deacetylation and molecular weight.
Chitosans with different degrees of deacetylation (DD) and molecular weights (Mw) were tested for the flocculation of bentonite suspensions prepared with demineralized water (DW) and tap water (TW), respectively. Flocculation kinetics model of particles collisions combining zeta potential and turbidity measurements was employed to investigate the effects of the DD and Mw of the chitosans on the flocculation properties. The results indicated that the chitosan (Mw 232 kDa) dosages required for maximum flocculation are 20 mg/L in DW and 5 mg/L in TW, respectively, regardless of DD from 54.6% to 95.2% and pH of bentonite suspension. Chitooligomers (Mw 1.5 kDa, DD 95.2%) failed to reach the required residual turbidity (i.e., 10 NTU) in DW under all investigated conditions, whereas good results were obtained using 5-20 mg/L in TW. The polymer-induced flocculation processed obeyed Von Smoluchowski's bimolecular rate equation. The flocculation performance in TW was very different from that in DW due to the presence of salts in TW. The results were consistent with the destabilization of bentonite by the combined mechanisms of charge neutralization and bridging.


Sural nerve grafts for delayed repair of divided posterior interosseos nerves.
Sural nerve grafts were used in three patients to bridge gaps measuring 2 1/2 to 4 1/2 cm in previously transected but not repaired posterior interosseous nerves. The grafts were done at 4, 5, and 7 months after injury. Extension was weaker in all three than on the uninjured side, but the range of motion was complete, with the exception of a slight lag of index finger extension and partial return of extension of the extensor carpi ulnaris in the same patient. All three patients recovered full function of the involved hand 1 year after grafting. The properties of the posterior interosseous nerve (pure motor and short distance to the muscle) contribute to good results with nerve grafts in delayed nerve repairs. We believe that these results are better than tendon transfers, at least in young patients.


Intraoperative three-dimensional scanning of head and neck surgical defects: Enhanced communication and documentation of harvested supplemental margins.
We have demonstrated the effectiveness of 3D resection specimen scanning for communicating margin results. We now address the corresponding surgical defect by debuting 3D defect models, which allow for accurate annotations of harvested supplemental margins. Surgical defects were rendered into 3D models, which were annotated to document the precise location of harvested supplemental margins. 3D defect scans were also compared with routine 2D photography and were analyzed for quality, clarity, and the time required to complete the scan. Forty defects were scanned from procedures including segmental mandibulectomy, maxillectomy, and laryngopharyngectomy. Average duration of defect scan was 6 min, 45 s. In six of ten 2D photographs, the surgeon was unable to precisely annotate the extent of at least one supplemental margin. 3D defect scanning offers advantages in that this technique enables documentation of the precise location and breadth of supplemental margins harvested to address margins at-risk.


Rapid Community Innovation: a Small Urban Liberal Arts Community Response to COVID-19.
Stories of community resilience and rapid innovation have emerged during the global pandemic caused by COVID-19. As communities, organizations, and individuals have had to shift modalities during the pandemic, they have identified ways to sustain community well-being. Prior to COVID-19, colleges and universities were hailed as anchors of economic and social resilience and well-being for communities of place. In this light, this commentary highlights stories of rapid community innovation occurring at Hobart & William Smith Colleges in the Finger Lakes region of New York. A series of vignettes are presented showcasing lessons and on-going questions regarding rapid pivots, community values, and diversity and inclusion during (and after) the pandemic. Overall, these insights can inform future local collaborative development efforts post-COVID-19 between colleges/universities and their local community.


SarA positively controls bap-dependent biofilm formation in Staphylococcus aureus.
The biofilm-associated protein Bap is a staphylococcal surface protein involved in biofilm formation. We investigated the influence of the global regulatory locus sarA on bap expression and Bap-dependent biofilm formation in three unrelated Staphylococcus aureus strains. The results showed that Bap-dependent biofilm formation was diminished in the sarA mutants by an agr-independent mechanism. Complementation studies using a sarA clone confirmed that the defect in biofilm formation was due to the sarA mutation. As expected, the diminished capacity to form biofilms in the sarA mutants correlated with the decreased presence of Bap in the bacterial surface. Using transcriptional fusion and Northern analysis data, we demonstrated that the sarA gene product acts as an activator of bap expression. Finally, the bap promoter was characterized and the transcriptional start point was mapped by the rapid amplification of cDNA ends technique. As expected, we showed that purified SarA protein binds specifically to the bap promoter, as determined by gel shift and DNase I footprinting assays. Based on the previous studies of others as well as our work demonstrating the role for SarA in icaADBC and bap expression, we propose that SarA is an essential regulator controlling biofilm formation in S. aureus.


Ending lethal discrimination against people with serious mental illness.
Each year in England 33 000 people diagnosed with a serious mental illness (SMI) die from causes that could have been avoided. Our mental-health-specific Atlas of Variation is the first to demonstrate the extent to which these inequalities and inequities affect mortality nationally.


Dimensions of loneliness.
Experiences of loneliness have been studied in 2795 Swedish inhabitants aged 15-80. Three different kinds of feelings of loneliness have been identified: intensity/quantity of loneliness, inner loneliness and positive loneliness. Contrary to common belief, the analysis shows that the intensity/quantity of loneliness is higher among young subjects whereas the degree of inner loneliness is slightly higher among older subjects. Both developmental experiences during childhood/adolescence and social conditions at present are correlated with the experience of loneliness in old people.


Achieving hunter-gatherer fitness in the 21(st) century: back to the future.
The systematic displacement from a very physically active lifestyle in our natural outdoor environment to a sedentary, indoor lifestyle is at the root of many of the ubiquitous chronic diseases that are endemic in our culture. The intuitive solution is to simulate the indigenous human activity pattern to the extent that this is possible and practically achievable. Suggestions for exercise mode, duration, intensity, and frequency are outlined with a focus on realigning our daily physical activities with the archetype that is encoded within our genome.


Complex Hereditary Spastic Paraparesis Caused by de novo p.Arg480Ser in FAR1.
FAR1 (MIM *616107) is required for the reduction of fatty acyl CoAs to fatty alcohols which is important for plasmalogen biosynthesis. Recently, heterozygous de novo variants in FAR1 have been associated with cataracts, spastic paraparesis, and speech delay (MIM# 619338). Three different heterozygous de novo variants, all located in the same codon, causing substitution of arginine at position 480 into cysteine, histidine, or leucine, were reported in patients in the latter disorder.Here, authors have identified a novel substitution in the same Arg480 position into serine. The authors also provide in silico docking analysis of the mutant protein.


Association between sleep stages and hunger scores in 36 children.
Childhood obesity is a growing health challenge. Recent studies show that children with late bedtime and late awakening are more obese independent of total sleep time. In adolescents and adults, a delayed sleep phase has been associated with higher caloric intake. Furthermore, an adult study showed a positive correlation between REM sleep and energy balance. This relationship has not been demonstrated in children. However, it may be important as a delayed sleep phase would increase the proportion of REM sleep. This study investigated the relationship between hunger score and sleep physiology in a paediatric population. Thirty-six patients referred for a polysomnogram for suspected obstructive sleep apnoea were enrolled in the study. Sleep stages were recorded as part of the polysomnogram. Hunger scores were obtained using a visual analogue scale. Mean age was 9.6 ± 3.5 years. Mean hunger scores were 2.07 ± 2.78. Hunger scores were positively correlated with percentage of total rapid eye movement (REM) sleep (r = 0.438, P < 0.01) and REM sleep duration in minutes (r = 0.471, P < 0.05). Percentage slow wave sleep (SWS) was negatively correlated with hunger score (r = -0.360, P < 0.05). There were no correlations between age, sex, body mass index percentiles, apnoea-hypopnoea index, total sleep time, sleep efficiency, sleep onset latency, stage 2 sleep duration and hunger scores. These findings suggest that delayed bedtime, which increases the proportion of REM sleep and decreases the proportion of SWS, results in higher hunger levels in children.


Naphthalene-induced hemolysis in a black female toddler deficient in glucose-6-phosphate dehydrogenase.
Hemolysis following accidental ingestion of naphthalene in black females deficient in glucose-6-phosphate dehydrogenase (G-6-PD) has not been previously reported. A 20-month-old black female is presented and the literature reviewed. Although G-6-PD deficiency is X-linked, health care providers must be aware that hemolysis may occur in females who are deficient in G-6-PD after exposure to naphthalene.


Ontogeny of islet cell antibodies, insulin autoantibodies and insulitis in the non-obese diabetic mouse.
The predictive value of insulitis, islet cell cytoplasmic antibodies and insulin autoantibodies for insulin-dependent diabetes was studied in young female non-obese diabetic mice. The ontogeny of the three markers was examined cross-sectionally at days 15, 25, 40 and 90 while islet cell antibodies and insulin autoantibodies were studied longitudinally from day 35 or day 144-168 until approximately day 250. Insulitis was first observed at day 40 (50%) and subsequently at day 90 (70%). Islet cell antibodies and insulin autoantibodies were present at day 15 in 46% and 54% of the animals respectively. The rate of islet cell antibodies was slightly higher at day 25 (60%) than at day 40 (40%) and day 90 (54%) whereas antibodies to insulin were present in all samples from day 25-90. At day 40 and day 90 insulitis and insulin autoantibodies were present together in 42% and 70% of the animals, respectively, while insulitis and islet cell antibodies had a lower rate of concordance (17% and 42%, respectively; diabetes rate, 30%). The concordance rates for islet cell antibodies and insulin autoantibodies were 42% at day 40 and 54% at day 90. Concordance for all three markers was first observed at day 40 (17%) which increased to 38% at day 90. In longitudinal studies, islet cell antibodies and insulin autoantibodies were often present together whether or not diabetes supervened. In the islet cell antibody procedure, immunoreactive cells were shown immunohistochemically to correspond with insulin and/or glucagon cells. However, this staining was not suppressible with insulin- or glucagon- absorbed sera, implying the presence of non-hormonal autoantigens. We conclude that the three markers investigated are expressed early after birth and well before clinical symptoms appear in this animal model. Both islet cell antibodies and insulin autoantibodies preceded insulitis but the prevalence rate for each marker or their degree of concordance was different from the anticipated rate of diabetes in our colony. Consequently, the early expression of the three markers alone is not predictive of diabetes although concordance for the two, or all three markers may be of some value. However, no animal developed diabetes without the prior appearance of both islet cell antibodies and insulin autoantibodies.


Role of non-governmental organizations in moving toward universal health coverage: A case study in Iran.
Delivering essential health services through non-governmental organizations (NGOs) could facilitate moving toward universal health coverage (UHC), especially in low- and middle-income countries. This study investigates the viewpoints of Iranian health system experts and executive stakeholders on the role of NGOs in moving toward UHC. We conducted 33 semi-structured interviews with health policymakers, NGO representatives at the national and provincial level, and other key informants and analyzed using content analyses methods, using MAXQDA 12. The inductive-deductive approach was used for qualitative data analyses. Based on the thematic analysis of interviews and document reviews, nine main themes and one hundred and five sub-themes were identified. Each theme was categorized based on NGO-, society-, and government-related factors. Recognizing the critical role of NGOs and their contribution in moving toward UHC is essential, particularly in the local context. Collaboration between NGO stakeholders and the government could facilitate moving toward UHC.


Interactive whiteboard use in clinical reasoning sessions to teach diagnostic test ordering and interpretation to undergraduate medical students.
Over-testing of patients is a significant problem in clinical medicine that can be tackled by education. Clinical reasoning learning (CRL) is a potentially relevant method for teaching test ordering and interpretation. The feasibility might be improved by using an interactive whiteboard (IWB) during the CRL sessions to enhance student perceptions and behaviours around diagnostic tests. Overall, IWB/CRL could improve their skills. Third-year undergraduate medical students enrolled in a vertically integrated curriculum were randomized into two groups before clinical placement in either a respiratory disease or respiratory physiology unit: IWB-based CRL plus clinical mentoring (IWB/CRL + CM: n = 40) or clinical mentoring only (CM-only: n = 40). Feasibility and learning outcomes were assessed. In addition, feedback via questionnaire of the IWB students and their classmates (n = 233) was compared. Analyses of the IWB/CRL sessions (n = 40, 27 paperboards) revealed that they met validated learning objectives. Students perceived IWB as useful and easy to use. After the IWB/CRL + CM sessions, students mentioned more hypothesis-based indications in a test ordering file (p < 0.001) and looked for more nonclinical signs directly on raw data tests (p < 0.01) compared with students in the CM-only group. Last, among students who attended pre- and post-assessments (n = 23), the number of diagnostic tests ordered did not change in the IWB/CRL + CM group (+ 7%; p = N.S), whereas it increased among CM-only students (+ 30%; p < 0.001). Test interpretability increased significantly in the IWB/CRL + CM group (from 4.7 to 37.2%; p < 0.01) but not significantly in the CM-only group (from 2.4 to 9.8%; p = 0.36). Integrating IWB into CRL sessions is feasible to teach test ordering and interpretation to undergraduate students. Moreover, student feedback and prospective assessment suggested a positive impact of IWB/CRL sessions on students' learning.


Scanning electron microscopic observation of the parasitic forms of Fonsecaea pedrosoi in a human skin lesion.
The parasitic form of Fonsecaea pedrosoi in the superficial hyperkeratotic layer of the skin, in a patient with chromoblastomycosis, was observed by a scanning electron microscope using some technical improvements. The fungus elements were comprised of branched septate hyphae with spherical cells and sclerotic cells. It was observed that the sclerotic cells, divided into two or three parts, formed a germ tube.


Aorta remodeling responses to distinct atherogenic stimuli: hypertension, hypercholesterolemia and turbulent flow/low wall shear stress.
This review is based on recently published data from our laboratory. We investigated the role of hypertension and laminar flow, hypercholesterolemia and laminar flow and turbulent blood flow/low wall shear stress, and turbulent blood flow/low wall shear stress associated with hypercholesterolemia on aorta remodeling of rats feeding normal diet or hypercholesterolemic diet. Our findings suggest that increased circumferential wall tension due to hypertension plays a key role in the remodeling through biomechanical effects on oxidative stress and increased TGF-beta expression; the remodeling observed in the presence of hypercholesterolemia could be initiated by oxidative stress that is involved in several processes of atherogenesis and this remodeling is more pronounced in the presence of turbulent blood flow/low wall shear stress.


A-kinase anchoring protein 13 interacts with the vitamin D receptor to alter vitamin D-dependent gene activation in uterine leiomyoma cells.
To determine if A-kinase anchoring protein 13 (AKAP13) interacts with the vitamin D receptor (VDR) to alter vitamin D-dependent signaling in fibroid cells. Uterine leiomyomas (fibroids) are characterized by a fibrotic extracellular matrix and are associated with vitamin D deficiency. Treatment with vitamin D (1,25-dihydroxyvitamin D3) reduces fibroid growth and extracellular matrix gene expression. A-kinase anchoring protein 13 is overexpressed in fibroids and interacts with nuclear hormone receptors, but it is not known whether AKAP13 may interact with the VDR to affect vitamin D signaling in fibroids. Laboratory studies. Translational science laboratory. Human immortalized fibroid or myometrial cells were treated with 1,25-hydroxyvitamin D3 (1,25(OH)2D3) and transfected using expression constructs for AKAP13 or AKAP13 mutants, RhoQL, C3 transferase, or small interfering ribonucleic acids (RNAs). Messenger ribonucleic acid (mRNA) levels of AKAP13, fibromodulin, and versican as measured by quantitative real-time polymerase chain reaction. Glutathione S-transferase-binding assays. Vitamin D-dependent gene activation as measured by luciferase assays. 1,25(OH)2D3 resulted in a significant reduction in mRNA levels encoding AKAP13, versican, and fibromodulin. Small interfering RNA silencing of AKAP13 decreased both fibromodulin and versican mRNA levels. Glutathione S-transferase-binding assays revealed that AKAP13 bound to the VDR through its nuclear receptor interacting region. Cotransfection of AKAP13 and VDR significantly reduced vitamin D-dependent gene activation. RhoA pathway inhibition partially relieved repression of vitamin D-dependent gene activation by AKAP13. These data suggest that AKAP13 inhibited the vitamin D receptor activation by a mechanism that required, at least in part, RhoA activation.


Phase transitions of heliconical smectic-C and heliconical nematic phases in banana-shaped liquid crystals.
A mean-field theory is introduced to describe heliconical nematic (N_{TB}), heliconical smectic-C (S_{m}C_{TB}), and biaxial heliconical smectic-C (S_{m}C_{TB,b}) phases with mirror symmetry breaking. We extend our previous theories of the N_{TB} phase to the heliconical smectic-C phases, by taking into account one-dimensional spatial ordering of smectic layers. The calculated phase diagrams on the temperature-alkyl chain length plane show a rich variety of phase transitions: first- and second-order N_{TB}-S_{m}C_{TB} transitions, etc., including tricritical, tetracritical, and multicritical points. Our theory is qualitatively consistent with an experimental phase diagram.


Uncovering the prominent role of satellite cells in paravertebral muscle development and aging by single-nucleus RNA sequencing.
To uncover the role of satellite cells (SCs) in paravertebral muscle development and aging, we constructed a single-nucleus transcriptomic atlas of mouse paravertebral muscle across seven timepoints spanning the embryo (day 16.5) to old (month 24) stages. Eight cell types, including SCs, fast muscle cells, and slow muscle cells, were identified. An energy metabolism-related gene set, TCA CYCLE IN SENESCENCE, was enriched in SCs. Forty-two skeletal muscle disease-related genes were highly expressed in SCs and exhibited similar expression patterns. Among them, Pdha1 was the core gene in the TCA CYCLE IN SENESCENCE; Pgam2, Sod1, and Suclg1 are transcription factors closely associated with skeletal muscle energy metabolism. Transcription factor enrichment analysis of the 42 genes revealed that Myod1 and Mef2a were also highly expressed in SCs, which regulated Pdha1 expression and were associated with skeletal muscle development. These findings hint that energy metabolism may be pivotal in SCs development and aging. Three ligand-receptor pairs of extracellular matrix (ECM)-receptor interactions, Lamc1-Dag1, Lama2-Dag1, and Hspg2-Dag1, may play a vital role in SCs interactions with slow/fast muscle cells and SCs self-renewal. Finally, we built the first database of a skeletal muscle single-cell transcriptome, the Musculoskeletal Cell Atlas (http://www.mskca.tech), which lists 630,040 skeletal muscle cells and provides interactive visualization, a useful resource for revealing skeletal muscle cellular heterogeneity during development and aging. Our study could provide new targets and ideas for developing drugs to inhibit skeletal muscle aging and treat skeletal muscle diseases.


Patient information in phase 1 trials: A systematic review.
To review what is known about cancer patients' decisions to enter a phase 1 trial and how they and their relatives perceive the information they receive when they are invited to participate. This systematic review is based on the principles of "preferred reporting items for systematic reviews and meta-analyses." A systematic search was performed in the PubMed, Embase, and PsycInfo databases, supplemented by a search for unpublished literature. We identified 37 studies for inclusion in this review. Patients' decisions to participate in a phase 1 trial were influenced by the drug being tested, information procedures, physician-related factors, and the patient's individual approach to decision making. Patients have difficulties correctly repeating the purpose of a phase 1 trial. In several studies, most patients expressed expectations of personal benefit from participating. Studies performing analyses of the dialog demonstrated that the language of the physicians was incomplete. The relatives' perceptions of such information remain unexplored. Most studies had a comprehensive risk of bias. Patients' decisions regarding participation in phase 1 trials are based on more than the information of the trial. The way patients express the information they have been given could be limited by the applied methods for evaluating this variable. While relatives are expected to be resources for patients entering a phase 1 trial, this topic has not been investigated.


[Management of flows and supply shortages of health products in hospitals during the COVID-19 crisis].
The hospital pharmacy is a medico-technical department within the hospital which has been significantly affected by the COVID-19 crisis. It has been a crucial element in the supply and flow management of medicines and medical devices. The shortage of medicines, and in particular of five molecules essential for the treatment of COVID-19 patients, has resulted in stocks being managed on a national level in order to address these new and unknown challenges. Adaptability will remain the key word to describe the action of hospital pharmacies during this crisis.


Undiversion using ileocecocystoplasty in a case of retroperitoneal hemorrhage after cardiac catheterization.
We performed urinary undiversion using ileocecocystoplasty in a patient who sustained bladder and ureteral necrosis secondary to transfemoral cardiac catheterization.


Evaluating the feasibility, effectiveness and costs of implementing person-centred follow-up care for childhood cancer survivors in four European countries: the PanCareFollowUp Care prospective cohort study protocol.
Long-term survival after childhood cancer often comes at the expense of late, adverse health conditions. However, survivorship care is frequently not available for adult survivors in Europe. The PanCareFollowUp Consortium therefore developed the PanCareFollowUp Care Intervention, an innovative person-centred survivorship care model based on experiences in the Netherlands. This paper describes the protocol of the prospective cohort study (Care Study) to evaluate the feasibility and the health economic, clinical and patient-reported outcomes of implementing PanCareFollowUp Care as usual care in four European countries. In this prospective, longitudinal cohort study with at least 6 months of follow-up, 800 childhood cancer survivors will receive the PanCareFollowUp Care Intervention across four study sites in Belgium, Czech Republic, Italy and Sweden, representing different healthcare systems. The PanCareFollowUp Care Intervention will be evaluated according to the Reach, Effectiveness, Adoption, Implementation and Maintenance framework. Clinical and research data are collected through questionnaires, a clinic visit for multiple medical assessments and a follow-up call. The primary outcome is empowerment, assessed with the Health Education Impact Questionnaire. A central data centre will perform quality checks, data cleaning and data validation, and provide support in data analysis. Multilevel models will be used for repeated outcome measures, with subgroup analysis, for example, by study site, attained age, sex or diagnosis. This study will be conducted in accordance with the guidelines of Good Clinical Practice and the Declaration of Helsinki. The study protocol has been reviewed and approved by all relevant ethics committees. The evidence and insights gained by this study will be summarised in a Replication Manual, also including the tools required to implement the PanCareFollowUp Care Intervention in other countries. This Replication Manual will become freely available through PanCare and will be disseminated through policy and press releases. Netherlands Trial Register (NL8918; https://www.trialregister.nl/trial/8918).


A Golgi study on the neuronal morphology in the hypothalamus of the Japanese quail (Coturnix coturnix japonica). I. Tuberal and mammillary regions.
Neuronal morphology and dendritic architecture of the tuberal and mammillary regions in the hypothalamus of the quail (Coturnix coturnix japonica) were investigated by means of classical neuroanatomical methods (Bodian silver impregnation, Luxol-fast blue, cresyl violet, toluidine blue, rapid Golgi method). The tuberal region is characterized by isodendritic neurons, in particular: a) pyriform and bipolar neurons, occasionally arranged diagonally to the ventricular surface; b) CSF-contacting neurons, located subependymally or more deeply in the periventricular gray, which are especially abundant in the paraventricular organ and in the proximity of the median eminence; c) numerous multipolar neurons, endowed with stout, almost unbranched dendritic processes, occupying generally the medio-lateral areas of the hypothalamus. Some multipolar neurons display somata, pyramidal or ovoidal in shape, almost imperceptibly tapering into three or more dendritic trunks. These relatively straight and long dendrites are rich in dendritic spines. In the mammillary region, Golgi impregnation shows multipolar neurons of medium size, most likely belonging to the lateral mammillary nucleus.


Arg462Gln sequence variation in the prostate-cancer-susceptibility gene RNASEL and age of onset of hereditary non-polyposis colorectal cancer: a case-control study.
RNASEL is thought to be a susceptibility gene for hereditary prostate cancer and encodes the endoribonuclease RNase L, which has a role in apoptosis and is a candidate tumour-suppressor protein. A common sequence variation in RNASEL, Arg462Gln, has been associated with hereditary and sporadic prostate cancer, and the Gln variant has about three-fold reduced RNase activity in vitro. In view of the association between the age of onset of hereditary non-polyposis colorectal cancer and functionally different variants of P53, which play a key part in the apoptotic pathway, we aimed to assess whether the Arg462Gln variation of RNASEL affects the age of onset of hereditary non-polyposis colorectal cancer. We screened 251 patients with hereditary non-polyposis colorectal cancer who were unrelated, had pathogenic germline mutations in MSH2 (n=141) or MLH1 (n=110), and had colorectal carcinoma as the first tumour, for variation at codon 462 of RNASEL and compared them with 439 healthy controls. The median age of onset was 40 years (range 17-75) for patients with an Arg/Arg genotype at codon 462, 37 years (13-69) for patients with an Arg/Gln genotype, and 34 years (20-49) for those with a Gln/Gln genotype (p=0.0198). Only the RNASEL genotype had a significant effect on age of onset (p=0.0062) in an additive mode of inheritance. Pair-wise comparisons between genotype groups showed that the two homozygous groups (ie, Arg/Arg vs Gln/Gln) differed significantly in age of disease onset (mean age difference 4.8 years [SD 1.7], p=0.0044). A sequence variation in the prostate-cancer-susceptibility gene RNASEL has a role in a different, unassociated malignant disease. Genotypes at RNASEL codon 462 are associated with age of onset of hereditary non-polyposis colorectal cancer in a dose-dependent way, and might have a role in preventive strategies for this disease.


Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl peptidase IV inhibitors.
A novel series of non-covalent, benzimidazole-based inhibitors of DPP-4 has been developed from a small fragment hit using structure-based drug design. A highly versatile synthetic route was created for the development of SAR, which led to the discovery of potent and selective inhibitors with excellent pharmaceutical properties.


Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding.
The metabolic stress-sensing enzyme AMP-activated protein kinase (AMPK) is responsible for regulating metabolism in response to energy supply and demand. Drugs that activate AMPK may be useful in the treatment of metabolic diseases including type 2 diabetes. We have determined the crystal structure of AMPK in complex with its activator 5-(5-hydroxyl-isoxazol-3-yl)-furan-2-phosphonic acid (C2), revealing two C2-binding sites in the γ-subunit distinct from nucleotide sites. C2 acts synergistically with the drug A769662 to activate AMPK α1-containing complexes independent of upstream kinases. Our results show that dual drug therapies could be effective AMPK-targeting strategies to treat metabolic diseases.


Calcaneal cuboid joint motion and osteotomy stability in children one year after calcaneal lengthening osteotomy.
Flexible pes planovalgus in children may be corrected with a calcaneal lengthening osteotomy (CLO).However, CLO surgery may displace the distal calcaneal fragment dorsally and affect the motion in the calcaneal-cuboid joint (CCJ). We used radiostereometric analysis (RSA) to evaluate CCJ motion and CLO stability in children one year after CLO. Ten patients (10 feet) with symptomatic flexible pes planovalgus were investigated one year after CLO. Mean age was 11.5 years (range 8.2-14.2). Standardised RSA measurements of the foot were obtained one year after surgery without and with weight-bearing (single leg stance). Tantalum markers inserted during surgery, were used to described the CCJ motion as cuboid bone motion with respect to the distal calcaneus, and the CLO stability as distal calcaneal migration with respect to the proximal calcaneus. One year after surgery the CLO was stable. The motion in the CCJ upon full weight-bearing was mean -1.04 mm (CI95% -1.40; -0.67) joint distraction, mean 2.27 mm (CI95% 1.57; 2.96) cuboid dorsal translation, mean -1.94 mm (CI 95% -2.68; -1.20) cuboid medial translation, and mean 7.43° (CI 95% 3.97; 10.88) adduction. The motion in the CCJ of children with CLO corrections for pes planovalgus is similar to that of adults during stance load with a normal foot posture and the patients were asymptomatic. Marker-based RSA may be used to evaluate causalities of foot symptoms after CLO surgery.


Oxidative compensation mechanism of Fe-S synergetic inhibition of Cd activity in paddy field during flooding and drainage.
It is known that the transformation of Fe and S forms in soil affects the migration and activity of Cd, but the coordinated regulation of Cd activity by Fe and S under different redox conditions is still unclear. Here, Diffusive gradients in thin films (DGT), an in-situ monitoring technique, is used to explore the difference of the regulation of Cd activity in paddy fields with ferrihydrite (FH) and ferrihydrite coprecipitated by sulfate (FH-S) under the flooding and drainage conditions. The addition of FH-S and FH significantly reduced the activity of Cd (Dissolved, Exchanged, and CDGT-Cd). Compared with pure FH, the adsorption extent of Cd in FH was enhanced by increasing concentrations of SO42- (i.e., S/Fe ratio), which is attributed to the decrease in the crystallinity of FH by sulfate. During soil flooding, the addition of FH-S promoted the production of metal sulfide (CdS and FeS/FeS2). The activity of Cd increased after drainage, while the FH-S treatment groups delayed the release of Cd. After 30 days of drainage, the concentration of Cd in FH-S treatment groups decreased by 28.9-44.1 % compared with the control group. The fresh FeS/FeS2 is not the main adsorbent for fixing Cd, and due to the existence of oxidation compensation mechanism, the preferential oxidation of FeS/FeS2 delays the release of Cd in the drainage stage. Our study shed new light on the mechanism of Fe-S synergistic regulation of Cd and remediation of Cd-contaminated soils.


Salidroside attenuates high altitude hypobaric hypoxia-induced brain injury in mice via inhibiting NF-κB/NLRP3 pathway.
Salidroside (Sal), an active ingredient from Rhodiola crenulate, has been reported to exert neuroprotection in cerebral injury from hypobaric hypoxia (HH) at high altitude. However, it remains to be understood whether its protective effects are related to inflammation suppression. In the present work, we aimed to reveal the mechanism of Sal attenuating HH-induced brain injury in mice caused by an animal hypobaric and hypoxic chamber. Our results provided that Sal could attenuate HH-evoked pathological injury and oxidative stress response by decreasing the content of ROS and MDA, and elevating the activities of SOD and GSH-Px. Sal treatment could partly enhance the energy metabolism, evidenced by increasing the activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, ATP, SDH, HK and PK, while decreasing the release of LDH and LD. Meanwhile, Sal administration reversed the degradation of tight junction proteins ZO-1, Occludin and Claudin-5. Further, the increased levels of TNF-α, IL-1β and IL-6 were confined with Sal administration under the HH condition. Importantly, Sal could downregulate the proteins expression of p-NF-κB-p65, NLRP3, cleaved-Caspase-1 and ASC. Sal also decreased the protein expression of iNOS and COX2 with the increased CD206 and Arg1 expression. Taken together, these data provided that the inhibited NF-κB/NLRP3 pathway by Sal could attenuate HH-induced cerebral oxidative stress injury, inflammatory responses and the blood brain barrier (BBB) damage, attributing to the improved energy metabolism and the microglial phenotype of anti-inflammatory M2. The findings suggested that Sal was expected to be a promising anti-inflammatory agent for high altitude HH-induced brain injury.


Expression of Drosophila Rrp1 protein in Escherichia coli. Enzymatic and physical characterization of the intact protein and a carboxyl-terminally deleted exonuclease-deficient mutant.
Drosophila Rrp1 protein purified from embryos has four tightly associated enzymatic activities: DNA strand transfer, single-strand DNA renaturation, 3'-exonuclease, and apurinic endonuclease. Copurifying with these activities is a single polypeptide that has an apparent M(r) of 105,000 when estimated by SDS-polyacrylamide gel electrophoresis. To determine if this polypeptide is sufficient for these activities, it has been overexpressed in Escherichia coli. In crude extracts of E. coli cells, an ATP-independent Mg(2+)-dependent strand transfer activity is observed upon activation of the promoter that drives expression of Rrp1. Rrp1 protein purified from induced E. coli cells has electrophoretic, chromatographic, and enzymatic properties similar to those of Drosophila Rrp1 protein. The carboxyl-terminal region of Rrp1 (amino acids 428-679) is homologous to E. coli exonuclease III. Rrp1 deleted for this region cannot carry out DNA strand transfer, but can renature complementary single-strand DNA. The strand transfer activity of this truncated protein can be restored if DNA 3'-exonuclease is provided in trans by pretreating the double-strand DNA substrate with E. coli exonuclease III. This demonstrates a likely role of the exonuclease in the in vitro DNA strand transfer reaction carried out by Rrp1 protein. Such a role is also suggested by an analysis of the polarity of the strand transfer reaction.


Family Doctor Contract Services and Awareness of Blood Pressure Measurement Among Hypertension Patients: A Cross-Sectional Study in Rural Shandong, China.
Some studies found that family doctor contract services (FDCSs) had positive impact on the self-measurement behaviors of hypertension patients. However, evidence concerning the association between FDCSs and blood pressure measurement awareness among hypertension patients is not clear. This study aims to explore the relationship between FDCSs and blood pressure measurement awareness among the hypertension patients, and examine whether there is a difference in this relationship among middle-aged and aged adults in rural Shandong, China. A multi-stage stratified random sampling was adopted in 2018 in Shandong Province to conduct a questionnaire survey among the sample residents, in which 982 hypertension patients were included in the study. Pearson chi-square test and logistic regression model were employed using SPSS 24.0 to explore the association between FDCSs and blood pressure measurement awareness. 76.8% of hypertension patients would measure blood pressure regularly. The blood pressure measurement awareness of the signing group was significantly higher than that of the non-signing group when controlling other variables (P < 0.001, OR = 2.075, 95% CI 1.391-3.095). The interaction of age and contracting status were significantly correlated with blood pressure measurement awareness (P = 0.042, OR = 1.747, 95% CI 1.020-2.992; P = 0.019, OR = 2.060, 95% CI 1.129-3.759). Factors including gender (P = 0.011, OR = 0.499, 95% CI 0.291-0.855), household income (P = 0.031, OR = 1.764, 95% CI 1.052-2.956), smoking status (P = 0.002, OR = 0.439, 95% CI 0.260-0.739), sports habits (P < 0.001, OR = 2.338, 95% CI 1.679-3.257), self-reported health (P = 0.031, OR = 1.608, 95% CI 1.043-2.477), distance to the village clinic (P = 0.006, OR = 1.952, 95% CI 1.208-3.153) and medications (P < 0.001, OR = 3.345, 95% CI 2.282-4.904) were also found to be associated with the blood pressure measurement awareness of hypertension patients. The government should take efforts to strengthen publicity and education of family doctors and pay more attention to uncontracted, middle-aged, female patients and patients with unhealthy life behaviors to improve the blood pressure measurement awareness.


New treatments for SLE: cell-depleting and anti-cytokine therapies.
Although systemic lupus erythematosus (SLE) is indeed a complex autoimmune disease, recent advances in our understanding of lupus pathogenesis have suggested new, targeted approaches to therapy. The purpose of this review is to discuss the underlying scientific rationale and results of first clinical studies of new treatment approaches to SLE, with a focus on cell-depleting therapies and cytokine blockade. It has become clear that the B lymphocyte plays a key role in disease pathogenesis by both autoantibody-dependent and autoantibody-independent mechanisms. Additionally, aberrant interactions between B and T cells are critical to disease emergence and progression. New agents that directly target immune cells abnormal in SLE include the B-cell depleting or modulating antibodies, rituximab (anti-CD20) and epratuzumab (anti-CD22) and the anti-dsDNA tolerogen LJP394. Another promising approach has been to block co-stimulatory interactions between T and B cells, for example by inhibiting the CD40-CD40 ligand pathway with anti-CD40 ligand monoclonal antibody or the B7 pathway with CTLA-4Ig. Immune cells can also be manipulated indirectly through cytokine effects. For B cells, anti-BAFF (B-cell activation factor of the tumor necrosis family) provides an example of this approach. Other, more pleiotropic cytokines can likewise be blocked in SLE. In addition to the blockade of interleukin-10 (IL-10), the first anti-cytokine approach examined, it is mainly anti-tumor necrosis factor therapy that has come into focus, holding promise for some patients with lupus nephritis. The majority of the available data on these new treatment approaches stems from open-label trials, but controlled trials are under way. Moreover, many additional cytokines, such as interleukin (IL)-6, IL-18, and the type I interferons, represent interesting future targets.


Short-term outcomes of anterior cruciate ligament reconstruction with or without lateral tenodesis or anterolateral ligament reconstruction: a retrospective cohort.
This study aimed to compare the short-term outcomes of ACL reconstruction (ACLR) alone, ACLR with lateral tenodesis, and ACL and ALL reconstruction. A retrospective cohort of prospectively collected data on all ACL procedures was performed at Aspetar Specialized Orthopaedic and Sports Medicine Hospital between January 2020 and January 2021. Patients were treated with ACLR alone, ACLR with lateral tenodesis, or ACLR with ALL reconstruction. The primary outcome was the subjective International Knee Documentation Committee (sIKDC) score. The secondary outcomes were the ACL Return to Sport after Injury (ACL-RSI) scores, pivot shift grade, subjective knee stability, and subjective pain on activity. A total of 100 cases were included. The most common technique was ACLR with lateral tenodesis (42%), followed by ACLR alone (38%) and ACL with ALL reconstruction (20%). The mean age was 28.15 years (15-60), and 94% of the patients were males. Meniscal procedures were more frequent in the ACLR alone group (65.8%). There was no association between subjective stability, sIKDC, ACL-RSI, and pivot shift grade and the three ACLR techniques while adjusting for age, sex, and concomitant meniscus procedures at six weeks, 12 weeks, six months, and nine months. However, there was a significant decrease in postoperative flexion in the ACL and ALL reconstruction group by a mean of 22° (95% CI - 40.7 - 3.4; P = 0.02) at 6 weeks compared to ACLR alone, which was not evident on later follow-ups. ACLR with/without lateral augmentation procedures yields similar subjective IKDC, ACL-RSI, pivot shift grade, and subjective knee instability at short-term follow-up. Therefore, lateral extra-articular augmentation procedures are safe to be performed.


Autoimmune hemolytic anemia and immune thrombocytopenia as unusual presentations of childhood Hodgkin lymphoma: a case report and review of the literature.
We discuss an unusual clinical presentation of childhood Hodgkin lymphoma; a 16-year-old girl was referred for Coombs-positive severe anemia, thrombocytopenia, and asymptomatic anterior mediastinal mass. Bone marrow examination showed no evidence of neoplastic disease. Biopsy of the mass was possible only after administration of both intravenous immunoglobulins and steroids resulting in a prompt rise of the platelet count and partial hemoglobin level stabilization. The identification of this clinical picture as a possible complication of an underlying Hodgkin lymphoma presents difficulties in diagnosis and management of the primary condition.


Nitroglycerin infusion during upright tilt: a new test for the diagnosis of vasovagal syncope.
The aim of our present study was to assess the value of nitroglycerin infusion during upright posture as a new provocative test for diagnosis of vasovagal syncope. To this purpose 40 patients with unexplained syncope (17 men and 23 women, mean age 47 years) and 25 asymptomatic control subjects with negative baseline head-up tilt underwent two other tilting tests, one during nitroglycerin infusion and one during isoproterenol infusion. The protocol of the nitroglycerin test consisted of a maximum of five successive stages of 5 minutes in the supine position plus 10 minutes 80-degree upright tilt at progressively increasing infusion rates (increments of 0.86 microgram/kg/hr every stage). During the nitroglycerin test a positive response (syncope in association with sudden hypotension and bradycardia) occurred in 21 (53%) patients with unexplained syncope, an exaggerated response (minor symptoms in association with slowly increasing hypotension alone) occurred in 10 (25%), a negative response in 9 (22%), and drug intolerance in 0. During the isoproterenol test these percentages were 25%, 25%, 32%, and 18%, respectively. Only 2 (8%) control subjects had a positive response to nitroglycerin test and 2 (8%) to isoproterenol test. Thus the nitroglycerin test seems to be a useful alternative tool for diagnosis of vasovagal syncope; it is equally specific but more sensitive and feasible than the isoproterenol test.


Plant antitumor agents. 25. Total synthesis and antileukemic activity of ring A substituted camptothecin analogues. Structure-activity correlations.
Nineteen racemic ring A substituted analogues of the antitumor agent 20(S)-camptothecin were prepared by total synthesis and evaluated for in vitro cytotoxic activity against KB cell culture and in vivo antileukemic activity against L1210. These compounds bore a wide variety of substituents at C11 designed to confer upon the ring system a broad range of combinations of electronic, steric, and lipophilic effects. A few C10-substituted derivatives as well as C10,C11-disubstituted analogues prepared as part of a concurrent study have also been included for general comparison. With the notable exception of the cyano derivative, the 11-substituted compounds displayed only modest in vitro and in vivo activities, and there was a remarkable insensitivity toward the nature of the substituent. In contrast, the 9- and 10-substituted compounds exhibited a considerably higher level of dose potency and activity both in vitro and in vivo.


Outcomes of cognitive behaviour therapy for obsessive-compulsive disorder in young people with and without autism spectrum disorders: A case controlled study.
Obsessive-compulsive disorder (OCD) and autism spectrum disorders (ASD) are highly co-morbid. It is suggested that youth with ASD will respond less well to cognitive behaviour therapy (CBT), as compared to their typically developing counterparts. To date there is no empirical evidence to support this view. The current study sought to compare CBT for OCD outcomes among youth with and without ASD. 22 young people with ICD-10 diagnoses of OCD and ASD (OCD+ASD) were matched with 22 youth with OCD, but no ASD (OCD+NoASD) according to base line OCD symptom severity, age, and gender. Outcomes were assessed for the two groups following a course of individually tailored, but protocol-driven CBT for OCD. While both groups responded to treatment the OCD+ASD group's outcomes were inferior to the OCD+NoASD group, as indicated by a significantly smaller decrease in symptoms over treatment (38.31% vs. 48.20%) and lower remission rates at post-treatment (9% vs. 46%). Overall, young people experiencing OCD in the context of ASD benefitted from CBT, but to a lesser extent than typically developing children. Recent efforts to modifying standard CBT protocols for OCD in ASD should continue in order to optimise outcomes among youth with this particular dual psychopathology.


Aqueous solution processed MoS3 as an eco-friendly hole-transport layer for all-inorganic Sb2Se3 solar cells.
Here we report a solution processed environmentally friendly MoS3 hole-transport material for Sb2Se3 solar cells, where MoS3 exhibits a matched energy level relative to Sb2Se3. In the synthesis, H2S produced by the thermal decomposition of (NH4)2MoS4 is found to efficiently eliminate the antimony oxide impurity formed on the Sb2Se3 surface. Finally, the all-inorganic Sb2Se3 solar cell delivers an efficiency of 6.86% with excellent stability.


Post-infarct cardiac rupture: recent insights on pathogenesis and therapeutic interventions.
Ventricular wall rupture represents a catastrophic complication of myocardial infarction (MI) in the clinic while research has long been hampered due to absence of suitable animal models. Since late 1990s, the mouse has become a suitable model for human post-infarct cardiac rupture. Here we review the clinical features of post-infarct rupture, factors associated with a higher risk of rupture, and findings from clinical trials on the incidence of post-infarct rupture. The features of the mouse model of post-infarct cardiac rupture are discussed. Research using this model suggests acute ventricular remodeling as the fundamental change leading to rupture, and has defined several key factors that determine the risk of rupture. We then provide a comprehensive review of the progress of experimental research in this field focusing on recent findings from genetically modified mouse models and experimental therapeutic interventions that reveal molecular mechanisms of post-infarct rupture. Genetic and pharmacological interventions targeting key inflammatory mediators, regulatory factors of extracellular matrix collagen and healing process effectively reduced the risk of rupture. These findings convincingly demonstrate that cardiac inflammation, damage to extracellular matrix proteins or blunted fibrotic healing constitute the central mechanisms for the pathogenesis of cardiac rupture and acute ventricular remodeling. Studies using the mouse model have also identified novel molecular mechanisms and therapeutic targets as well as suitable interventional regimens providing useful clues for clinical translation.


The management of genital lymphoedema.
To report our experience and management of genital lymphoedema, as this condition can be extremely debilitating and difficult to manage. The clinical records of 90 patients with genital lymphoedema who presented between 1998 and 2007 were retrospectively reviewed. The surgical management of 34 patients consisted of the excision of the affected skin and of the subcutaneous layers. This involved scrotal excision in 15 patients with primary closure. Skin grafts were required in seven patients for penile shaft cover. The results for cosmesis, recovery of sexual function, patient's satisfaction and complications are discussed. In all, 56 patients were successfully managed conservatively by treating the underlying condition, antibiotic administration, compression and elevation of the genitalia. The remaining 34 patients required surgical management with an overall excellent cosmetic result and a significant improvement in sexual function. When surgery is necessary for genital lymphoedema, the new techniques described provide excellent cosmetic and functional results.


HPLC determination of chloramphenicol degradation in eye drops.
An HPLC-method is described for the simultaneous determination of chloramphenicol and its most important degradation products. A 15 cm long C-18 reversed phase column was used with a mobile phase consisting of boric acid solution-acetonitrile (60 + 45) adjusted to a pH of 3. The amount of degradation of chloramphenicol eye drop solutions containing boric acid and borax, at pH 4.7 and 7.2 respectively, is determined at 4, 21, 100 and 120 degrees C. The solution of pH 7.2 is more stable than that of pH 4.7 at 4 and 21 degrees C, but is less stable at 100 and 120 degrees C. Preparation has to be accomplished in subdued light. The solutions have to be protected from light during storage.


Iodine status of 8 to 10 years old children within 20 years following compulsory salt iodization policy in Shanghai, China.
In 1996, Shanghai implemented universal salt iodization and has became the last provincial unit in China to carry out this intervention. In this study, we summarized achievements in past 20 years, to provide suggestions and evidence for the next stage of iodine supplementation. This study summarized and analyzed monitoring data of children from 1997, 1999, 2005, 2011, 2014, and 2017 in Shanghai. In each monitoring year, 30 streets or towns were selected using the probability-proportional-to-size sampling technique. One primary school was selected from each street or town by a simple random sampling technique. From each school, 40 children aged 8 to 10 years were randomly selected. The number of children was divided equally by sex and age. In 1997, 1999, 2005, 2011, 2014, and 2017, median urinary iodine (MUI) was 227.5 μg/L, 214.3 μg/L, 198.1 μg/L, 181.6 μg/L, 171.4 μg/L, and 183.0 μg/L, goiter rate was 3.07, 0.40, 0.08, 0.08, 0.86, and 1.90%, and median thyroid volume (MTvol) was 2.9 mL, 1.2 mL, 2.4 mL, 1.0 mL, 1.8 mL, and 2.8 mL, respectively. There was a linear correlation between goiter rate and median thyroid volume (MTvol) (r = 0.95, P = 0.014). Household salt iodine concentration (SIC) was dropping every monitoring (P < 0.05). There was a significant difference among different household SIC groups in MUI in 1999 and 2017, and in MTvol in 1999 (P < 0.05). No significant differences were detected in the other years. In Shanghai, the iodine status of 8 to 10 years old children is adequate. Household SIC have little effect on iodine status of children. Future studies should analyze the dietary sources of iodine, especially from pre-packaged and prepared-away-from-home foods or meals. The regular monitoring of iodine status is important to human health.


Identification of a novel HLA-A allele, HLA-A*9216.
The new human leukocyte antigen (HLA)-A*9216 differs from A*02010101 by a nonsynonymous nucleotide change at condon 76 (GTG>CTG).


Multislice CT: update on radiation and screening.
With ever-expanding applications, increasing availability, and accessibility of CT scanners, concerns have been raised about radiation exposure associated with CT scanning. Global statistics and projections suggest increasing use of CT scanning and its contribution to radiation exposure is a cause for concern. Several strategies based on modulation of scanning parameters and technologic improvisations have been developed in an effort to reduce associated radiation dose. This article discusses the basis for rising concern regarding radiation dose associated with CT scanning. The fundamentals of CT dose estimation are described along with strategies that aim to reduce radiation dose associated with CT scanning based on patient characteristics, study indications, and technological innovations.


The impact of demographic and self-management factors on physical activity in women.
Guided by the Individual and Family Self-Management Theory, this study examines demographic and self-management variables that impact the outcome of physical activity. Multiple sources indicate relationships between physical activity and reduced incidence of cardiovascular disease. Women engage in significantly less physical activity than guidelines recommend. Data collected in women included demographic/situational factors and external influencing level factors including knowledge and beliefs, social facilitation, and outcome expectancy. The outcome behavior physical activity was also assessed. Correlation and hierarchical multiple regression were used to examine the relationship of demographic/situational and external influencing factors to physical activity. The sample included 119 women (mean age 40.96, 89.1% Caucasian, 51.3% Married, 95% high school graduates). Education was positively correlated with exercise benefits (r = 0.235,p = .010). Gross family income (r = 0.191,p = .043), work status (r = 0.238,p = .009), and health insurance(r = 0.228,p = .013) were positively correlated to family participation, and work status was positively correlated to friend participation (r = 0.263.p = .004). In the final model, demographic/situational factors (step 1) explained 12.9% of the variance in physical activity (p < .05). Knowledge and beliefs, social support, and outcome expectancy (step added an additional 0.9% of variance physical activity levels). Findings suggest that demographic/situational factors contribute more to explaining variability in physical activity levels than external influencing factors. This suggests that in addition to considering demographic variables, further research to explore other demographic/situational and external influencing factors that affect physical activity specifically in women is necessary.


Transcriptional and post-transcriptional control of cold-shock genes.
A mesophile like Escherichia coli responds to abrupt temperature downshifts (e.g. from 37 degrees C to 10 degrees C) with an adaptive response that allows cell survival and eventually resumption of growth under the new unfavorable environmental conditions. During this response, bulk transcription and translation slow or come to an almost complete stop, while a set of about 26 cold-shock genes is preferentially and transiently expressed. At least some of the proteins encoded by these genes are essential for survival in the cold, but none plays an exclusive role in cold adaptation, not even the "major cold-shock protein" CspA and none is induced de novo. The majority of these proteins binds nucleic acids and are involved in fundamental functions (DNA packaging, transcription, RNA degradation, translation, ribosome assembly, etc.). Although cold-induced activation of specific promoters has been implicated in upregulating some cold-shock genes, post-transcriptional mechanisms play a major role in cold adaptation; cold stress-induced changes of the RNA degradosome determine a drastic stabilization of the cold-shock transcripts and cold shock-induced modifications of the translational apparatus determine their preferential translation in the cold. This preferential translation at low temperature is due to cis elements present in the 5' untranslated region of at least some cold-shock mRNAs and to trans-acting factors whose levels are increased substantially by cold stress. Protein CspA and the three translation initiation factors (IF3 in particular), whose stoichiometry relative to the ribosomes is more than doubled during the acclimation period, are among the trans elements found to selectively stimulate cold-shock mRNA translation in the cold.


Arterial oxygen desaturation in adult dental patients receiving conscious sedation.
Forty-six adults undergoing dental procedures were monitored with a pulse oximeter for hypoxemia. Thirty-six patients received various amounts and combinations of central nervous system depressant drugs (barbiturates, sedatives, and narcotics) in addition to local anesthetics to produce a state of conscious sedation. Twenty-eight patients in the latter group received supplemental oxygen. Ten subjects served as a control group and received only local anesthesia without supplemental oxygen. Continuous monitoring by pulse oximetry revealed 151 episodes of mild, 132 of moderate, and 33 of severe arterial oxygen desaturation, although clinical signs of hypoxemia were absent. Patients with a body mass index greater than 30 or those with a smoking history greater than 30 pack-years were particularly prone to arterial oxygen desaturation.


Short term ketamine treatment in patient with bipolar disorder with comorbidity with borderline personality disorder: Focus on impulsivity.
Borderline personality disorder (BPD) and bipolar disorder (BD) often co-occur and frequently do not respond adequately to traditional antidepressant treatments. Ketamine has shown rapid antidepressant and anti-suicidal effects. However, there is limited literature on the safety and tolerance of using ketamine to treat patients with comorbid BD and BPD. This case presents a female patient diagnosed with both Bipolar Disorder (BD) and Borderline Personality Disorder (BPD) who received intravenous ketamine treatment to alleviate acute depressive symptoms. Initially, ketamine ameliorated depressed symptoms. However, as the ketamine treatment continued, the patient showed an increase in nonsuicidal self-injury (NSSIs) and impulsive conduct with a aggravation of dissociative symptoms. As a result, intravenous ketamine was discontinued, and the patient received the medication, which proved helpful. Although ketamine presents antidepressant properties, reports on its impact on emotional dysregulation and impulsive conduct are unclear and not alike to its antidepressant effect. Therefore, there is a need for more studies investigating the effectiveness and safety of this rapid-acting medicine in this patient population.


Hyperdense Middle Cerebral Artery Sign Together with Pulmonary Thromboembolism.
Hyperdense middle cerebral artery sign is an appearance of the middle cerebral artery on non-contrast-enhanced computed tomography. Embolic occlusion of the pulmonary arterial system is referred to as pulmonary embolism. When pulmonary embolism coexists with a patent foramen ovale, increased pressure in the right atrium may result in widening of the foramen and consequently, cause serious conditions due to paradoxical embolus. Coexistence of hyperdense middle cerebral artery sign and pulmonary thromboembolism is very rare in the literature. We presented a 60-year-old female patient who had both hyperdense middle cerebral artery sign and pulmonary thromboembolism. To our knowledge, togetherness of hyperdense MCA sign and pulmonary thromboembolism is extremely rare in the literature. In our case, we found both pulmonary embolism due to DVT and paradoxical embolism due to existing patent foramen ovale.


The Porphyromonas gingivalis inhibitory effects, antioxidant effects and the safety of a Sri Lankan traditional betel quid - an in vitro study.
The Sri Lankan traditional betel quid (TBQ) which had been extensively used in the country before its colonization is claimed to have antiperiodontopathic effects in the Sri Lankan folklore. However, there is no reported scientific evidence to support the claimed antiperiodontopathic effects mediated by this TBQ. The present study was carried out to investigate the protective effect of the Sri Lankan TBQ in the pathogenesis of periodontitis. We investigate the ethyl acetate extract of the Sri Lankan TBQ for its antibacterial effects against the keystone periodontopathic bacterium, P. gingivalis and also its antioxidant potential, which is important to protect the periodontium from oxidative stress. Further, its safety was analyzed using the cytokinesis block micronucleus assay on human peripheral blood lymphocytes (PBLs). Ethyl acetate extract of this TBQ inhibited the growth of P. gingivalis with a minimum bactericidal concentration (MBC) of 125 μg/ml. It was found to be a rich source of polyphenols and displayed considerable DPPH and ABTS radical scavenging activities and a strong ferric reducing antioxidant power. This extract could protect the cultured human gingival fibroblasts from H2O2 induced oxidative stress. In addition, this TBQ extract was not genotoxic to human PBLs even at a concentration of 2.5 mg/ml. Moreover, it exhibited protective effects against bleomycin induced genotoxicity in PBLs. Ethyl acetate extract of the Sri Lankan TBQ is a source of natural antibacterial compounds against P. gingivalis. It is also a source of natural antioxidants which can protect human gingival fibroblasts from H2O2 induced oxidative stress. These properties of the TBQ may have contributed to its claimed antiperiodontopathic effects. Besides, it was found to be relatively non-toxic to human cells. Thus this TBQ extract has a huge potential to be developed as a novel adjunctive therapeutic lead against periodontitis.


Residual urine as a risk factor for lower urinary tract infection: a 1-year follow-up study in nursing homes.
To determine whether postvoid urine is a risk factor for the development of lower urinary tract infections (UTIs) in nursing home residents. Prospective surveillance with a follow-up period of 1 year. Six Norwegian nursing homes. One hundred fifty nursing home residents. Postvoid residual (PVR) urine volumes were measured using a portable ultrasound. UTIs were registered prospectively for 1 year. Ninety-eight residents (65.3%) had a PVR less than 100 mL, and 52 (34.7%) had a PVR of 100 mL or greater. During the follow-up period, 51 residents (34.0%) developed one or more UTIs. The prevalence of UTI in women was higher than in men (40.4% vs 19.6%; P=.02). There was no significant difference in mean PVR between residents who did and did not develop a UTI (79 vs 97 mL, P=.26). PVR of 100 mL or greater was not associated with greater risk of developing a UTI (P=.59). High PVR is common in nursing home residents. No association between PVR and UTI was found.


A microfilaria in a stray cat from Assiut, Egypt.
During a survey for helminth parasites among stray cats in Assiut area, microfilariae were detected. The morphology of the microfilarias was described.


Effects of tranexamic acid and bipolar sealer alone or in combination in primary total knee arthroplasty: a prospective, randomized, controlled trial.
The purpose of this study was to compare 2 blood management interventions, tranexamic acid (TXA) and bipolar sealer system (BSS) used independently or in combination with a control group during primary total knee arthroplasty (TKA). A total of 127 TKA patients were enrolled and randomized into 4 groups: Intravenous TXA plus the BSS (N = 29, group 1); TXA only (N = 29, group 2); BSS only (N = 31, group 3); and intravenous normal saline as a control group (N = 32, group 4). Changes in hemoglobin from baseline to postoperative follow-up were significantly lower among patients who received TXA plus BSS and those receiving TXA only when compared with the control. BSS only did not differ significantly when compared to the control group. In addition, TXA plus BSS was as efficacious as TXA only in preserving postoperative hemoglobin. In other terms, using bipolar sealer did not add to the effect of TXA in reducing the postoperative hemoglobin drop in primary TKA.


Glycoconjugate biosynthesis in human epidermis.
Epidermal glycoconjugates synthesized by skin slices in media containing radiolabelled sugars were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. A large proportion of the epidermal glycoconjugates were soluble in 10% (w/v) trichloroacetic acid. In addition to glycolipids and glycosaminoglycans, the acid-soluble fraction contained glycoproteins, a group of which (mol. wt. 70,000-160,000) were highly glycosylated and particularly rich in fucose. Analysis of the glycosaminoglycans by cellulose acetate electrophoresis combined with specific enzymic and nitrous acid degradation studies revealed that hyaluronic acid (73%) and heparan sulphate (18%) were the main components.


Energy, transport, and consumption in the Industrial Revolution.
We question Baumard's underlying assumption that humans have a propensity to innovate. Affordable transportation and energy underpinned the Industrial Revolution, making mass production/consumption possible. Although we cannot accept Baumard's thesis on the Industrial Revolution, it may help explain why complexity and innovation increase rapidly in the context of abundant energy.


Single-Cell RNA-Seq Steps Up to the Growth Plate.
Single-cell RNA sequencing (RNA-seq) technology is hitting its stride and is beginning to be widely adopted. One of the major challenges faced by this rapidly growing field lies in data analysis. Li et al. now present Sinova, a single-cell analytical platform offering temporal, spatial, and regulatory reconstruction of developmental processes.


How possible is the prevention of polycystic ovary syndrome development in adolescent patients with early onset of hyperandrogenism.
The polycystic ovary syndrome has a pubertal onset, with menstrual cycle irregularities and infertility in adulthood, as well as general health hazards such as increased risk for diabetes mellitus and myocardial infarction. Thus, prevention would be important. But as specific etiological factors are not known, nor is specific intervention. In order to use long-term intervention programs in children and adolescents, particularly rigid criteria must be used regarding proven safety and efficacy. In obese subjects, weight loss is very important, having beneficial effects on most aspects of the syndrome, such as subjective symptoms, infertility, hyperinsulinemia and related metabolic aberrations, and long-term health risks. Well controlled, long-term follow-up studies are needed on the role of prepubertal hyperandrogenism, hyperinsulinemia, gonadotropins, and ovarian morphological aspects in the development of PCOS, and possibilities of prevention.


Increased expression of TGF-beta1 reduces tumor growth of human U-87 Glioblastoma Cells in vivo.
The role that transforming growth factor beta1 (TGF-beta1) plays in influencing growth of glioma cells is somewhat controversial. To further understand the potential growth-regulatory effects of TGF-beta1,we constructed an animal astroglial tumor model by injecting either wild-type or virally transduced human U-87 glioblastoma cells into nude rat brains. Wild type U-87 cells produced very low amounts of TGF-beta1 and were highly tumorigenic. In contrast, U-87 cells transduced to express high levels of TGF-beta1 showed reduced tumor size in vivo, in a dose-dependent manner. This reduction in tumor size was not due to either decreased vascularity or increased apoptosis. To test whether TGF-beta1 overproduction inhibited tumor growth through an autocrine mechanism, the highest TGF-beta1 producing cells were then double transduced with a vector expressing the kinase-truncated type II TGF-beta receptor. Cells expressing high levels of truncated TGF-beta receptor were less sensitive to TGF-beta1 mediated growth inhibition in vitro and produced more aggressive tumors in vivo. The data suggest that the degree of tumorigenicity of the U-87 high-grade glioblastoma cell line may be associated with correspondingly low level of production of TGF-beta1. These results also would tend to support the possibility that TGF-beta1 may be useful in treating some high-grade gliomas.


Expression of Total Vascular Endothelial Growth Factor and the Anti-angiogenic VEGF 165 b Isoform in the Vitreous of Patients with Retinopathy of Prematurity.
This study was to examine the expression of total vascular endothelial growth factor (VEGF) and the anti-angiogenic VEGF 165 b isoform in the vitreous body of retinopathy of prematurity (ROP) patients, and to further study the role of the VEGF splicing in the development of ROP. This was a prospective clinical laboratory investigation study. All patients enrolled received standard ophthalmic examination with stage 4 ROP that required vitrectomy to collect the vitreous samples. The control samples were from congenital cataract patients. The expression of total VEGF and the anti-angiogenic VEGF 165 b were measured by enzyme-linked immunosorbent assay. Results were analyzed statistically using nonparametric tests. The total VEGF level was markedly elevated in ROP samples while VEGF 165 b was markedly decreased compared to control group. The relative protein expression level of VEGF 165 b isoform was significantly decreased in ROP patients which were correlated with the ischemia-induced neovascularization. There was a switch of VEGF splicing from anti-angiogenic to pro-angiogenic family in ROP patients. A specific inhibitor that more selectively targets VEGF 165 and controls the VEGF splicing between pro- and anti-angiogenic families might be a more effective therapy for ROP.


Clinico-pathological findings in diarrhoea-negative haemolytic uraemic syndrome.
This is a retrospective, national clinico-pathological study of past and current patients with haemolytic uraemic syndrome not associated with diarrhoea (D- HUS). Thirty-four patients were analysed and notified by members of the British Association for Paediatric Nephrology in 1998-1999. There was a 2:1 excess of males. Ten presented in infancy. The aetiology included 5 patients with complement abnormalities, 2 patients with complications of pneumococcal infection, and 2 with malignancies. Parental consanguinity was noted in 6 patients. Five children died, 9 developed chronic renal failure, and 10 end-stage renal failure. Only 7 made full recoveries. With a single exception, the pathological findings were unlike the previously reported glomerular thrombosis that is characteristic of diarrhoea-associated HUS, or HUS complicating verocytotoxin-producing Escherichia coli infection. Early and late glomerulopathy could be distinguished. Arteriolar and arterial disease was observed in 8 and 7 patients, respectively. Arterial disease correlated with a poor outcome. The pathology of D- HUS is of prognostic value, but this study was not powered to identify specific aetiological/pathological correlations.


Polymorphisms of genes encoding interleukin-4 and its receptor in Iranian patients with juvenile idiopathic arthritis.
As cytokines, including interleukin-4 (IL-4), seem to have a pivotal role in the pathogenesis of juvenile idiopathic arthritis (JIA), this study is aimed at investigating of association of polymorphisms in IL-4 and IL-4 receptor α (IL-4RA) genes with susceptibility to JIA. A case-control study was conducted on 53 patients with JIA and 139 healthy unrelated controls. Single nucleotide polymorphisms of IL-4 gene at positions -1098, -590, and -33, as well as IL-4RA gene at position +1902 were genotyped using polymerase chain reaction with sequence-specific primers method and compared between patients and healthy individuals. At the allelic level, C allele at IL-4 -33 was found to be more frequent in patients compared to control (P value <0.01). At the genotypic level, CC genotype at IL-4 -590 (P value <0.01), together with CC and TT genotypes at IL-4 -33 (P value <0.01), were significantly higher in patients with JIA, while TC genotypes at IL-4 -590 and -33 positions were found to be lower in case group (P value <0.01). At the haplotypic level, IL-4 (positions -1098, -509, -33) TTC, GCC, and TTT haplotypes were significantly lower than controls (P value <0.01, P value = 0.03, and P value = 0.04, respectively). Although, TCC haplotype at the same positions was found to be higher in patients (P value <0.01). Polymorphic site of +1902 IL-4RA gene did not differ between cases and controls. Polymorphisms in promoter region of IL-4 but not IL-4RA genes confer susceptibility to JIA and may predispose individuals to adaptive immune responses.


Folinic acid, 5-fluorouracil and etoposide after curative resection for gastric cancer.
The aim of this study was to evaluate the survival benefit of adjuvant chemotherapy with etoposide, leucovorin and 5-fluorouracil (ELF) in gastric cancer patients undergoing previous surgery with a curative intent. The clinical outcome of 49 patients with resected gastric cancer treated with adjuvant chemotherapy was compared with that of 85 surgically treated historical controls who did not receive any adjuvant treatment. The chemotherapy regimen consisted of six cycles of daily 1-hour intravenous infusions of folinic acid 100 mg/m2 and 5-FU 400 mg/ m2, and a 2-hour infusion of etoposide 100 mg/m2, for three days every 28 days. The 5-year relapse-free survival was 32% in the adjuvant arm and 27% in the control arm (p = 0.6). At the last follow-up, there were 32 deaths in the adjuvant arm and 60 in the control arm. The median duration of survival was respectively 23 and 19 months, and the 5-year survival rates were 34% and 29% (p = 0.4). The chemotherapy was well tolerated. Our data suggest that ELF adjuvant treatment is a safe and well tolerable combination chemotherapy in patients with resected gastric cancer, but it does not seem to improve prognosis in comparison with historical controls.


Oxidative stress stimulates IL-4 and IL-6 production in mast cells by an APE/Ref-1-dependent pathway.
Mast cells are exposed to an oxidative environment in the course of allergic and inflammatory reactions. We have examined the effects of H(2)O(2) stimulation in a primary rat basophilic leukemia cell line (RBL-2H3) and compared with IgE-dependent stimulation. Like IgE stimulation, H(2)O(2) up-regulates IL-4 and IL-6 gene expression and cytokine secretion, shows a little effect on IL-5 but does not induce IL-10 gene expression. Simultaneous H(2)O(2) treatment and FcepsilonRI triggering of mast cells has additive effects on IL-4 expression. In addition, we show that both stimuli induce the nuclear translocation of APE/Ref-1, a bifunctional enzyme that stimulates the DNA-binding activity of several transcription factors through the reduction of highly reactive cysteines. Conditional inactivation of APE/Ref-1 expression abolishes H(2)O(2)-induced IL-4 and IL-6 gene expression but does not affect that induced by FcepsilonRI stimulation. Our findings indicate that oxidative stress activates the gene expression of a specific cytokine pattern in mast cells through an APE/Ref-1-dependent pathway, which is distinct from the one that is activated by FcepsilonRI stimulation. Nonetheless, H(2)O(2) and FcepsilonRI signalings are additive in augmenting IL-4 production. Most importantly, oxidative stress can induce a pro-type 2 inflammatory response from mast cells that is independent of FcepsilonRI stimulation.