An inhibitory effect of schisandrone on α-hemolysin expression to combat methicillin-resistant staphylococcus aureus infections.
Due to increasing antibiotic resistance, targeting bacterial virulence factors is now gaining further interest as an alternative strategy to develop novel classes of anti-infective agents. The critical role of α-hemolysin (Hla), an indispensable virulence determinant, in the pathogenicity of Staphylococcus aureus renders this virulence factor an appealing target for effective therapeutic applications. Herein, we identified a natural compound schisandraone, as an effective Hla inhibitor, which could inhibit Hla production and thus hemolytic activity in a dose-dependent manner without affecting the growth of S. aureus. We also found that the addition of schisandrone could down-regulate the transcriptional levels of the hla, agrA and RNAIII and significantly alleviated Hla-mediated injury of A549 cells co-cultured with S. aureus. In vivo studies further suggested that schisandrone combined with antibiotic ceftiofur exhibited a significant therapeutic effect on S. aureus infection. These findings revealed the role of schisandrone in inhibiting the activity of Hla and we believe that it is a promising anti-virulence candidate to combat MRSA pneumonia.


Thyroid and parathyroid gland pathology. Role of imaging.
There are many imaging modalities available for studying thyroid and parathyroid masses. For the thyroid gland, the demonstration of a hyperfunctioning or purely cystic mass by scintigraphy and ultrasound reassures that a palpable nodule is not cancer. Solitary, cold, or solid nodules often requires biopsy because of suspicion of malignancy. Metabolic and inflammatory disorders are imaged best with nuclear medicine studies whereas congenital thyroid lesions are evaluated best with computed tomography or MR imaging. In the search for a parathyroid adenoma, MR imaging and technetium-99m sestamibi studies appear to be most accurate, but because of its low cost, ultrasound has a favorable role. In previously operated patients with persistent hyperparathyroidism, MR imaging is probably most useful, but multiple imaging studies may be needed for definitive localization of adenomas.


Integration of TeamSTEPPS Framework and Escape Room to Improve Teamwork and Collaboration.
As the need for healthcare professionals continues to grow, different learning environments have been assessed to optimize knowledge while keeping the student engaged. Escape rooms, live action, team-based exercises, supplemented with TeamSTEPPS tools can assist in overall team performance, while keeping the participant engaged in a new learning environment. The goal of this quality improvement project was to enhance teamwork and collaboration through the integration of TeamSTEPPS concepts and escape room active learning. This concept was explored through the integration of TeamSTEPPS tools and strategies in an escape room setting. The purpose was to improve team dynamics and cohesiveness in a new dynamic way with a small cohort of nurse leaders in a large urban academic medical center, while exploring the engagement and depth of learning experience for the participant. Twelve nurse leaders completed two different escape rooms while observers completed the TeamSTEPPS observation tool assessing team dynamics and performance and participants assessed their perceptions before and after intervention. These nurses also were observed at staff meetings and completed a perceptions tool on teamwork pre- and postintervention. A postescape room survey was completed by participants to assess learning and interest in this interactive learning exercise. There was a significant statistical difference after TeamSTEPPS and escape room intervention (Mean 17.3 and p = 0.004 SD 5.9) when compared to before intervention as well as has a more positive sense of teamwork was noted. In addition, 75% of the nurses strongly agreed that the escape room was engaging and fun with 25% agreeing. Ninety-one percent agreed or strongly agreed that the escape room was an effective team-building exercise with 100% agreeing or strongly agreeing to recommend the escape room experience to others. This cohort validated the integration of TeamSTEPPS tools and strategies in an escape room setting as an enjoyable and engaging way to learn while providing an effective team-building activity. This small cohort demonstrates that new methods of learning such as an escape room should be explored further for engaging participants and improving communication and teamwork skills. Integrating TeamSTEPPS into an escape room offers this institution a way to continue this project while providing valuable team-building skills to its participants. While this was just a small sample in one intercity hospital, new methods for learning should be reviewed for successful teamwork in nursing and in healthcare as a whole, as there was some data to suggest that utilizing an escape room could have a positive impact on team cohesiveness as well as leadership skills for the individual.


Reproductive potential of colonies of desert harvester ants (Pogonomyrmex desertorum): effects of predation and food.
To ascertain what factors affect reproductive output of colonies of the Desert Harvester Ant, Pogonomyrmex desertorum, colonies were subjected to two experiments. The first was a 3-way factorial design, which varied (i) artificial predation intensity, (ii) seed addition, and (iii) insect matter addition. The second experiment used fences to prevent horned lizards (Phrynosoma spp.) from foraging on concentrations of worker ants found at colony entrances. Increased artificial predation caused a decrease in alate production. The effect of predation was strongest in colonies also receiving insect matter. The treatments of adding seeds and adding insect matter by themselves did not have a measurable effect on alate production. Exclusion of horned lizard predators using fencing also had no effect on alate production. Although this study shows that predation has the potential to affect reproductive output (and therefore the potential to have been important in the evolutionary history of P. desertorum) the present study shows no evidence that either present levels of predation or scarcity of food limit reproductive output.


[Ni(CO)4 ]+ as NiI Synthon: Synthesis and Characterization of NiI Half-Sandwich and Sandwich Cations.
The stable, easily accessible salt [Ni(CO)4 ]+ [F{Al(ORF )3 }2 ]- (RF =C(CF3 )3 ) was used as a NiI synthon to generate the novel half-sandwich complexes [Ni(arene)(CO)2 ]+ (arene=C6 H6 , o-dfb=1,2-F2 C6 H4 ). By irreversible removal of CO from the equilibrium, even the rather endergonic reaction to a [Ni(o-dfb)2 ]+ salt was successful (Δr G°(solv) =+78 kJ mol-1 ). The latter displays an unprecedented slipped η3 ,η3 -sandwich structure and is the ultimate synthon to NiI -chemistry.


Students' interaction anxiety and social phobia in interprofessional education in Hong Kong: mapping a new research direction.
Interprofessional education (IPE) has been promoted as a breakthrough in healthcare because of the impact when professionals work as a team. However, despite its inception dating back to the 1960s, its science has taken a long time to advance. There is a need to theorize IPE to cultivate creative insights for a nuanced understanding of IPE. This study aims to propose a research agenda on social interaction by understanding the measurement scales used and guiding researchers to contribute to the discussion of social processes in IPE. This quantitative research was undertaken in a cross-institutional IPE involving 925 healthcare students (Medicine, Nursing, Social Work, Chinese Medicine, Pharmacy, Speech Language Pathology, Clinical Psychology, Food and Nutritional Science and Physiotherapy) from two institutions in Hong Kong. Participants completed the Social Interaction Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6). We applied a construct validation approach: within-network and between-network validation. We performed confirmatory factors analysis, t-test, analysis of variance and regression analysis. CFA results indicated that current data fit the a priori model providing support to within-network validity [RMSEA=.08, NFI=.959, CFI=.965, IFI=.965, TLI=.955]. The criteria for acceptable fit were met. The scales were invariant between genders, across year levels and disciplines. Results indicated that social interaction anxiety and social phobia negatively predicted behavioural engagement (F = 25.093, p<.001, R2=.065) and positively predicted behavioural disaffection (F = 22.169, p<.001, R2=.057) to IPE, suggesting between-network validity. Our data provided support for the validity of the scales when used among healthcare students in Hong Kong. SIAS-6 and SPS-6 have sound psychometric properties based on students' data in Hong Kong. We identified quantitative, qualitative and mixed methods research designs to guide researchers in getting involved in the discussion of students' social interactions in IPE.Key MessagesThe Social Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6) scales have sound psychometric properties based on the large-scale healthcare students' data in IPE in Hong Kong.Social interaction anxiety and social phobia negatively predicted students' behavioural engagement with IPE and positively predicted behavioural disaffection. The scales are invariant in terms of gender, year level and discipline.Quantitative, qualitative and mixed methods studies are proposed to aid researchers to contribute in healthcare education literature using the SIAS-6 and SPS-6.


Protein structure alignment.
A new method of comparing protein structures is described, based on distance plot analysis. It is relatively insensitive to insertions and deletions in sequence and is tolerant of the displacement of equivalent substructures between the two molecules being compared. When presented with the co-ordinate sets of two structures, the method will produce automatically an alignment of their sequences based on structural criteria. The method uses the dynamic programming optimization technique, which is widely used in the comparison of protein sequences and thus unifies the techniques of protein structure and sequence comparison. Typical structure comparison problems were examined and the results of the new method compared to the published results obtained using conventional methods. In most examples, the new method produced a result that was equivalent, and in some cases superior, to those reported in the literature.


Stiff-three limbs syndrome.
We report a patient diagnosed with stiff-three limbs syndrome, without continuous motor unit activity in the electrophysiologic exam, with successful treatment with intravenous immunoglobulin.


The Impact of Diabetes on Acute Kidney Injury After Off-Pump Coronary Artery Bypass Grafting.
Acute kidney injury (AKI) is one of the most frequent complications after coronary artery bypass grafting. Previous studies have shown that diabetes is a key pathogenic factor. But how diabetes is related to AKI in off-pump CABG patients still is in debate. Here, we aim to study the relationship between diabetes and AKI after off-pump coronary artery bypass grafting (off-pump CABG). Patients who underwent off-pump CABG from April 2017 to December 2020 in The First Affiliated Hospital of USTC were enrolled in this retrospective study. AKI was defined and classified, according to the criteria proposed by the Acute Kidney Injury Network. The incidence risk of acute kidney injury was measured by logistic regression and compared. A total of 395 patients, who underwent off-pump CABG, were included in this study. The postoperative acute kidney injury rate for a patient with diabetes was significantly higher than for patients without diabetes (x2 = 5.09, P = 0.024). Logistic regression analysis showed that patients with diabetes have a much higher risk with acute kidney injury occurring after off-pump coronary artery bypass grafting (OR 1.852, 95% CI 1.161 - 2.954, P = 0.01). Diabetes is an independent risk factor for postoperative AKI for patients undergoing off-pump CABG.


Paradoxical Sost gene expression response to mechanical unloading in metaphyseal bone.
The Sost gene encodes Sclerostin, an inhibitor of Wnt-signaling, generally considered a main response gene to mechanical loading in bone. Several papers describe that unloading leads to upregulation of Sost, which in turn may lead to loss of bone. These studies were based on whole bone homogenates or cortical bone. By serendipity, we noted an opposite response to unloading in the proximal rat tibia. Therefore, we hypothesized that Sost-expression in response to changes in mechanical load is bone site specific. One hind limb of male, 3 month old rats was unloaded by paralyzing the extensors with Botulinium toxin A (Botox) injections. A series of experiments compared the expression of Sost mRNA in the unloaded and contralateral, loaded limbs, after 3 or 10 days, in metaphyseal cancellous bone, metaphyseal cortical bone, and diaphyseal cortical bone. We also conducted μCT to confirm changes in bone volume density related to unloading. Sost mRNA expression in the cancellous metaphyseal bone was downregulated almost 2-fold, both 3 days and 10 days after unloading (P<0.05). A similar tendency was seen in the metaphyseal cortical bone, in which Sost was 1.5-fold downregulated (P<0.05) after 10days, but not significantly changed after 3days. In contrast, diaphyseal cortical Sost expression was instead upregulated 1.4-fold (P<0.05) following 3-day unloading, while there was no significant change after 10days. Cancellous bone volume density was 58% lower (P<0.001, compared to cage controls) in the unloaded limb but not significantly affected in the loaded limb. The results suggest that Sost mRNA expression in metaphyseal bone responds to mechanical unloading in an opposite direction to that observed in diaphyseal cortical bone. This proposes a more complex expression pattern for Sost in response to unloading. Therapeutics that target Sclerostin during altered loading conditions may result in local bone mass changes that are difficult to predict.


Long-term statin use in patients with lung cancer and dyslipidemia reduces the risk of death.
Clinical studies have obtained inconsistent results of statin use on cancer outcomes. This study investigated the association between statin use and lung cancer mortality. The use of statin decreased mortality (hazard ratio = 0.91; 95% confidence interval: 0.86-0.96; P < .01). The patients with a high cumulative defined daily dose of statin use before lung cancer diagnosis exhibited a low risk of mortality. We conducted a population-based case-control study of patients with dyslipidemia. Among them, 6270 had used statins for at least 3 months before lung cancer diagnosis, and 6270 had never used statins. We found that statin use can reduce lung cancer mortality. A further prospective study is necessary to confirm these findings.


A new test for the diagnosis of growth hormone deficiency due to primary pituitary impairment: combined administration of pyridostigmine and growth hormone-releasing hormone.
The diagnosis of growth hormone (GH) deficiency (GHD) is currently based on failure to increase plasma GH levels to an arbitrary cutoff point of 7 or 10 micrograms/l in response to two provocative stimuli. False negative responses to these tests, however, frequently occur thus reducing their diagnostic reliability. The aim of this study was to assess a combination of pyridostigmine (PD) and GH-releasing hormone (GHRH) (60 mg oral PD 60 min before 1 microgram/Kg GHRH iv) as a reliable test probing pituitary somatotropic function. In fact PD, an acetylcholinesterase inhibitor, strikingly potentiates GH response to GHRH likely by inhibiting somatostatin release. The combination PD + GHRH was tested in normal children and adolescents (NS, n = 27) and in a large group of short children classified as having familial short stature (FSS, n = 24), constitutional growth delay (CGD, n = 34) and GH deficiency (organic, oGHD, n = 6; idiopathic, iGHD, n = 10). In all groups results obtained by PD + GHRH were compared with those obtained by testing with GHRH, clonidine (CLON) and PD alone and by studying spontaneous nocturnal GH secretion over 8 hours. Assuming 7 micrograms/l as minimum normal GH peak, a positive response occurred in only 18/24, 11/12 and 12/13 NS for GHRH, CLON, and PD, respectively. In contrast even assuming a minimum normal GH peak as high as 20 micrograms/l, PD + GHRH induced a positive response in 27/27 NS all having a nocturnal GH mean concentration (MC) greater than or equal to 3 micrograms/l. Therefore PD + GHRH test gave no false negative responses and this was true not only in NS but even in all FSS and CGD having a GH MC greater than or equal to 3 micrograms/l. On the other hand, PD + GHRH induced a negative GH response in all oGHD and in 8/10 iGHD patients. In the remaining two iGHD patients, PD + GHRH demonstrated a normal pituitary GH reserve in spite of a GH MC less than 3 micrograms/l and low IGF-I level, thus pointing to a hypothalamic pathogenesis for the GHD. Considering FSS and CGD children having a GH MC less than 3 micrograms/l, PD + GHRH showed a primary pituitary GH deficiency in 3/12 CGD with low plasma IGF-I levels. In conclusion, in slowly growing children PD + GHRH test is the most reliable provocative test for the diagnosis of primary pituitary GH deficiency being capable to discriminate between an unequivocally normal and impaired somatotropic function.(ABSTRACT TRUNCATED AT 400 WORDS)


Clinical characteristics of adolescent endometrioma.
To evaluate the clinical characteristics of endometrioma in adolescent women compared to women of other age groups. Cross-sectional study. A university hospital. Three-hundred seventy-six women. Women of reproductive age who underwent surgery for the treatment of endometrioma were classified into 4 groups according to age (group 1, ≤20 years; group 2, 21-30 years; group 3, 31-40 years; group 4, 41-45 years), and compared. Clinical characteristics including demographic factors, menstrual patterns, and characteristics of endometriosis. Group 1 (adolescent females) experienced menarche at earlier age compared to other groups (P < .005 for all comparisons). In group 1, main symptom was pain (77%) and the proportion of incidental detection (23%) was low, similar to findings for group 2. However, the proportions of incidental detection (45%) and infertility (10%) were increased in group 3, and the proportion of incidental detection (60%) was even higher than that of pain (40%) in group 4 showing that the distributions of presenting symptoms differed from those of group 1. There were no differences in menstrual pattern among groups. In addition, except for the absence of coexisting gynecologic problems such as myoma or adenomyosis in group 1, other characteristics of endometrioma did not differ among groups. Adolescents with endometrioma experience more frequent pain, but other clinical characteristics are similar to adults.


Effect of Training and Level of External Auditory Feedback on the Singing Voice: Pitch Inaccuracy.
One of the most important aspects of singing is the control of fundamental frequency. The effects on pitch inaccuracy, defined as the distance in cents in equally tempered tuning between the reference note and the sung note, of the following conditions were evaluated: (1) level of external feedback, (2) tempo (slow or fast), (3) articulation (legato or staccato), (4) tessitura (low, medium, or high), and (5) semi-phrase direction (ascending or descending). The subjects were 10 nonprofessional singers and 10 classically trained professional or semi-professional singers (10 men and 10 women). Subjects sang one octave and a fifth arpeggi with three different levels of external auditory feedback, two tempi, and two articulations (legato or staccato). It was observed that inaccuracy was greatest in the descending semi-phrase arpeggi produced at a fast tempo and with a staccato articulation, especially for nonprofessional singers. The magnitude of inaccuracy was also relatively large in the high tessitura relative to the low and the medium tessitura for such singers. Contrary to predictions, when external auditory feedback was strongly attenuated by the hearing protectors, nonprofessional singers showed greater pitch accuracy than in the other external feedback conditions. This finding indicates the importance of internal auditory feedback in pitch control. With an increase in training, the singer's pitch inaccuracy decreases.


Chitosan-derived carbonaceous material for highly efficient adsorption of chromium (VI) from aqueous solution.
A carbonaceous adsorbent for effectively removing Cr(VI) was synthesized by facile hydrothermal carbonization of chitosan (HTC-chitosan). The prepared HTC-chitosan exhibited good stability in acid solution while the amine groups were retained completely after simple and green hydrothermal carbonization treatment. Structure characteristics of the HTC-chitosan as well as its adsorption behaviors for Cr(VI) in aqueous solution were investigated. Under optimal conditions, the adsorption capacity of the HTC-chitosan for Cr(VI) reached as high as 388.60mgg(-1), which was much higher than that of other materials reported previously. The prepared HTC-chitosan adsorbent could be reused at least five times with adsorption efficiency more than 92%. These results indicate that HTC-chitosan exhibited great superiority for Cr(VI) adsoption from aqueous solution both in terms of the preparation process and adsorption performance.


Verapamil-mediated atrioventricular nodal reentrant tachycardia and the uncovering of dual-pathway AV nodal conduction.
In a 67-year-old man with multiple myocardial infarctions in the past, the use of oral verapamil for control of angina pectoris was followed by the appearance of two previously undiagnosed abnormalities, namely, a dual-pathway AV node conduction pattern, and paroxysms of AV nodal reentrant tachycardia precipitated by premature ventricular beats (PVB). It is probable that the differential effects of verapamil on the fast and slow AV node pathways, and the interplay of PVB with its concealment within the AV node, created the necessary circumstances in the AV node to precipitate the tachycardia. Observed off verapamil over several months, the patient remained in normal sinus rhythm but continued to have numerous premature ventricular beats (PVB's). Nevertheless, neither the clinical electrocardiographic features of dual-pathway AV node conduction nor the AV nodal reentrant tachycardia could be found. The proarrhythmic effect of verapamil and its ability to provoke the very arrhythmia against which it is most effective are of particular interest in view of a similar behavior exhibited by the Class I antiarrhythmic agents.


Interaction of hydrophobic bis (D-mannose) derivatives with adipocyte and erythrocyte sugar transport systems.
The inhibition of sugar uptake by a series of hydrophobic bis(D-mannose) derivatives has been measured in rat adipocytes. When the D-mannose moieties of the bis compounds are separated by a hexane bridge the transport inhibition constant (Ki) is greater than for a decane-bridged molecule. This is probably due to the increased hydrophobicity of the bridge of the decane-bridged compound. The enhancement in affinity due to the second sugar in the bis(D-mannose) derivatives is probably only 2-fold, since half reduction of the bis(D-mannosyloxy)hexane increases Ki approx. 2-3-fold. N'-DNP-1,3-bis(D-mannos-4'-yloxy)propyl-2-amine has very high affinity in insulin-treated cells. The affinity is approx. 1000-fold higher than for D-mannose. This enhancement is probably due to the hydrophobicity of the DNP group. The distance from the sugar to the hydrophobic group is important because an increase in Ki occurs if an aminocaproyl spacer is introduced between the DNP group and 1,3-bis(D-mannos-4'-yloxy)propyl-2-amine. Aminocaproyl and glycyl spacers also increase the Ki for NAP derivatives of 1,3-bis(D-mannos-4'-yloxy)propyl-2-amine. Each of the hydrophobic bis(D-mannose) derivatives has a lower Ki in insulin-treated cells. This may be due to an insulin responsive hydrophobic interaction between the hydrophobic portion of the sugar and a hydrophobic domain in the transport system. The inhibition constants for the hydrophobic bis(D-mannose) compounds have also been measured in human erythrocytes.


Effects of electro-acupuncture on immune function after chemotherapy in 28 cases.
To observe the effects of electroacupuncture therapy on T cells and activity of NK cell in the patient of Chemotherapy. Electro-acupuncture therapy was simultaneously applied during chemotherapy, T cells and activity of NK cell of patients were determined before electroacupuncture treatment (before chemotherapy) and after 4-course electro-acupuncture treatments. Before chemotherapy, CD3 was low within the normal range, CD4 was much lower than the normal range, and CD8, CD4/CD8 and activity of NK cell were within the normal range. After one month of chemotherapy combined with electro-acupuncture, no decline of all the indices was found (P > 0.05). Electro-acupuncture can really increase the immune function of patients of chemotherapy.


Further characterisation of allergens associated with hypersensitivity to the "green nimitti" midge (Cladotanytarsus lewisi, Diptera: Chironomidae).
Chironomid midges are small (2-15 mm) non-biting flies, characteristically seen swarming by water at dusk. Allergens of the "green nimitti" midge, Cladotanytarsus lewisi (Freeman) (Diptera: Chironomidae), a cause of widespread hypersensitivity in the Sudan, were isolated and partially characterized by Sephacryl S200 chromatography. The allergenicity of the fractions was identified by "rocket" autoradiography, RAST inhibition, skin "prick" tests, and the immunoblot technique. The fractions were further analysed by isoelectric focusing and SDS-PAGE. Two major allergens with pI's ranging from 4.3 to 6.0 were identified and had molecular weights of approximately 17,000 and 32,000 daltons, sizes compatible with their being monomeric and dimeric haemoglobins. Since chironomids occur in nuisance numbers worldwide and their haemoglobins have been shown to produce severe hypersensitivity reactions in man, they should be seen as an important potential cause of environmental and occupational allergy.


Cooperative thermal denaturation of the assembly origin region of TMV RNA.
The assembly origin (AO) region of the tobacco mosaic virus RNA melts in an usually narrow (2.5 degrees C) temperature range. In an 0.01 M phosphate buffer the melting temperature of AO was found to be 41.5 degrees C. This value corresponds to the regions with the most stable secondary/tertiary structure of the whole TMV RNA molecule. It is assumed that the AO region has a specific tertiary structure, which is maintained by the long-range interactions as well as by interactions of the pseudoknot type.


Are results from pharmaceutical-company-sponsored studies available to the public?
Only 53% and 63% of studies and clinical trials results presented at congresses are published. Company-sponsored trial results are being posted on publicly accessible Web sites. We analyzed the public availability (publication or posting on a Web site) rate, time to publication, and factors predicting public availability of results of studies sponsored by a pharmaceutical company. This was a retrospective cohort study analyzing all studies conducted by GlaxoSmithKline in Spain between 2001 and 2006. Initiation and completion were defined as first participant/first visit and last participant/last visit (or their equivalents). Papers published up to 31 March 2009 were considered. Logistic regression models were used to identify factors predicting public availability of results. The cohort comprised 143 studies (94 clinical trials; of these, 87 were included in international products clinical development plans). Public availability rate was 80% (114/143) for all studies and 78% (73/94) for clinical trials; publication rates were 68% and 61%, respectively. The median time to publication for all studies and trials was 27.3 and 28.4 months, respectively. Study associated to a cancelled project was the only significant factor associated with lower publication rate for all studies [odds ratio (OR) 0.069; 95% confidence interval (CI) 0.02-024; p < 0.001) and trials (OR 0.075; 95% CI 0.016-0.343; p = 0.001) and a lower public availability rate (OR 0.052; 95% CI 0.007-0.382; p = 0.004) for trial results. Therapy area, sample size, positive trial results, duration of experimental phase, and being a clinical trial did not predict publication or public availability. Eighty percent of studies included in this analysis are publicly available. Web site posting increases public availability rate of clinical trial results from 61% to 78%. Cancellation of projects is the single factor negatively influencing publication and public availability rates.


Ultrasound-guided transvaginal ovarian needle drilling (UTND) for treatment of polycystic ovary syndrome: a randomized controlled trial.
To evaluate the outcome of ovarian needle drilling using transvaginal ultrasound guidance as an alternative to the traditional laparoscopic electrosurgical drilling for patients with polycystic ovary syndrome (PCOS). A randomized controlled study. University teaching hospital and private practice setting. The study comprised 163 patients with clomiphene-resistant PCOS. Patients were randomly allocated to either treatment with ultrasound-guided transvaginal needle ovarian drilling (UTND; n = 82) or laparoscopic electrosurgery ovarian drilling (n = 81). Hormonal changes (FSH, LH, T), ovulation and pregnancy. There were no significant differences between the two groups with regard to body mass index, hormonal profiles, clinical manifestations, and ultrasound findings of PCOS. The duration of UTND was 15.3 +/- 5.61 minutes (10.5-22.3 minutes), while it was 25.6 +/- 8.2 minutes (20.3-38.1 minutes) in laparoscopic drilling, with a statistically significant difference between the two groups. There were no significant differences between the two groups with regard to resumption of normal menstruation, hirsutism, acne, ovulation, and pregnancy. UTND resulted in significant improvement in the ovulation, pregnancy, hirsutism, and acne. There were significant decreases in the serum LH and T levels but not in the FSH or LH/FSH levels after UTND as well. UTND can be adopted as an outpatient office procedure. The ease of scheduling, reduced costs, and rapid recovery suggest it as a first-line treatment for PCOS cases resistant to clomiphene citrate.


How does RNA fold dynamically?
Recent advances in interrogating RNA folding dynamics have shown the classical model of RNA folding to be incomplete. Here, we pose three prominent questions for the field that are at the forefront of our understanding of the importance of RNA folding dynamics for RNA function. The first centers on the most appropriate biophysical framework to describe changes to the RNA folding energy landscape that a growing RNA chain encounters during transcriptional elongation. The second focuses on the potential ubiquity of strand displacement - a process by which RNA can rapidly change conformations - and how this process may be generally present in broad classes of seemingly different RNAs. The third raises questions about the potential importance and roles of cellular protein factors in RNA conformational switching. Answers to these questions will greatly improve our fundamental knowledge of RNA folding and function, drive biotechnological advances that utilize engineered RNAs, and potentially point to new areas of biology yet to be discovered.


Prediction of mutations engineered by randomness in H5N1 neuraminidases from influenza A virus.
In this proof-of-concept study, we attempt to determine whether the cause-mutation relationship defined by randomness is protein dependent by predicting mutations in H5N1 neuraminidases from influenza A virus, because we have recently conducted several concept-initiated studies on the prediction of mutations in hemagglutinins from influenza A virus. In our concept-initiated studies, we defined the randomness as a cause for mutation, upon which we built a cause-mutation relationship, which is then switched into the classification problem because the occurrence and non-occurrence of mutations can be classified as unity and zero. Thereafter, we used the logistic regression and neural network to solve this classification problem to predict the mutation positions in hemagglutinins, and then used the amino acid mutating probability to predict the would-be-mutated amino acids. As the previous results were promising, we extend this approach to other proteins, such as H5N1 neuraminidase in this study, and further address various issues raised during the development of this approach. The result of this study confirms that we can use this cause-mutation relationship to predict the mutations in H5N1 neuraminidases.


ABO-Incompatible Renal Transplantation with High Antibody Titer: A Case Report.
BACKGROUND Even though renal transplantation across blood groups is not uncommonly practiced nowadays, there is still hesitation regarding ABO-incompatible transplantation with very high baseline antibody titer. In this case report, the outcome of an ABO-incompatible kidney transplant recipient with a high baseline isoagglutinin titer is reported. CASE REPORT The patient was a non-diabetic, 33-year-old man with end-stage renal disease secondary to chronic glomerulonephritis. The only kidney donor available was his mother, who was blood-group incompatible. The patient's blood group was O positive, whereas his mother was B positive. We evaluated him for an ABO-incompatible renal transplant. The baseline anti-B isoagglutinin titer was >1:8196. With a desensitization protocol of low-dose Rituximab, plasmapheresis, and IVIG, this titer was brought down to 1:32 before transplantation. He successfully underwent renal transplantation across the ABO barrier, and maintains good graft function after 1 year of follow-up. CONCLUSIONS In the present era, a high baseline isoagglutinin titer is no longer a contraindication for successful kidney transplantation in ABO-incompatible recipient-donor pairs.


Letter to the Editor: SFlt-1 and PlGF Levels in Pregnancies Complicated by SARS-CoV-2 Infection.
We read with interest the work by Espino-y-Sosa and colleagues [...].


Femoral compressive neuropathy from iliopsoas haematoma complicating dengue hemorrhagic fever.
Dengue fever is a debilitating mosquito-borne disease caused by dengue virus. We reported a case of femoral compression neuropathy due to iliopsoas hematoma complicating dengue hemorrhagic fever. Iliopsoas muscle hematoma can cause femoral neuropathy with resultant pain and paralysis. Such manifestations are not well documented in the literature. The pathogenesis of hematoma and compressive neuropathy with its appropriate management is discussed.


Studying the Effects of Collagenase (Type 1) on the Collagen in Woody Breast Meat.
Abnormal collagen infiltration in the Pectoralis major, breast muscle, of fast-growing big broilers has led to woody breast (WB) myopathy resulting in meat quality issues. Mechanisms to degrade the collagen were investigated to potentially improve WB texture. Freshly deboned WB fillets (n = 5 per trial; 3 trials) were ground and divided in to 25 g portions. Aqueous collagenase Type I solution (1 mL) from concentrations of 2.5, 5, and 10 mg/mL were incorporated in ground WB samples (n = 3 samples/treatment × 3 trials). Ground WB with 1 mL water acted as a control. All the samples were placed at 4 °C for 24 h and frozen at -80 °C. Control samples without any treatment or water addition (n = 3/trial) were frozen immediately upon grinding. Data collected on total (TC), soluble (SC), and insoluble collagen (IC) content was analyzed using one-way ANOVA with Tukey's honestly significant difference (HSD) (p ≤ 0.05). Fresh WB fillets had TC, SC, and IC content of 19.5, 4.9, and 14.6 mg/g, respectively. The addition of collagenase decreased (p ≤ 0.05) the IC to 5.8 mg/g in the 10 mg/mL treatment after 24 h. Converting IC to SC using collagenase can potentially help the poultry industry to reduce WB toughness.


[Uniocular aphakia--conventional contact lenses and aniseikonia].
Ehrich and Kolbegger show in their papers that aniseikonia should not prevent binocular functions in a uniocular aphakia. This is contrary to our own experiences. In this paper we suggest that the results of Ehrich and Kolbegger must be worse in spite of their final conclusions. Their hypotheses are discussed.


Design and characterization of opioid ligands based on cycle-in-macrocycle scaffold.
The study reports on a series of novel cyclopeptides based on the structure Tyr-[d-Lys-Phe-Phe-Asp]NH2, a mixed mu and kappa opioid receptor agonist with low nanomolar affinity, in which Phe4 residue was substituted by cyclic amino acids, such as Pro or its six-membered surrogates, piperidine-2-, 3- or 4-carboxylic acids (Pip, Nip and Inp, respectively). All derivatives exhibited high mu- and moderate delta-opioid receptor affinity, and almost no binding to the kappa-opioid receptor. Conformational analysis suggested that the cis conformation of the peptide bond Phe3-Xaa4 influences receptor selectivity through the control of the position of Phe3 side chain. The results substantiate the use of the cycle-macrocyle scaffolds for fine-tuning receptor selectivity.


Antibiotic resistance of Helicobacter pylori to 16 antibiotics in clinical patients.
Resistance of Helicobacter pylori (H. pylori) to antibiotics is increasing worldwide. To determine the status of H. pylori resistance and its patterns in clinical patients, an investigation utilizing susceptibility testing for commonly used antibiotics was needed. Total of 2283 H. pylori strains were collected from 2013 to 2016. The resistance and its patterns of these strains were tested by agar dilution method. The resistance rate and minimal inhibition concentration (MIC) in different gender groups were also analyzed. The overall resistance rates were as following: amoxicillin (1.58%), clarithromycin (22.73%), levofloxacin (24.75%), furazolidone (1.49%), doxycycline (9.20%), cefetamet (97.20%), ceftriaxone (49.60%), cefuroxime (25.20%), gentamicin (3.73%), azithromycin (85.60%), rifampicin (2.80%), metronidazole (92.53%), ornidazole (94.27%), tinidazole (87.20%), ciprofloxacin (43.20%), and moxifloxacin (38.53%). There were only 64.08% strains pan-susceptible to amoxicillin, clarithromycin, levofloxacin, and furazolidone, followed by mono resistance (23.17%), double resistance (11.13%), triple resistance (1.36%), and quadruple resistance (0.26%). Significant differences in the resistance rate and MIC were also observed in different gender groups. Antibiotic resistance trends of H. pylori is increasing in clinical patients. With the increasing resistance, it is imperative to individualized therapy based on the results of drug susceptibility testing.


Diffusion and activity of antibiotics against Burkholderia pseudomallei biofilms.
The diffusion and activity of ceftazidime (CAZ), imipenem (IPM) and trimethoprim/sulfamethoxazole (TMP/SMX) against Burkholderia pseudomallei biofilms were comparatively tested using the high biofilm-producing strain B. pseudomallei 377 and the biofilm-defective mutant B. pseudomallei M6. Biofilms were generated by inoculation of bacteria on polycarbonate membranes placed on the surface of tryptic soy agar plates. The results showed that diffusion of TMP/SMX through B. pseudomallei biofilms was similar for both strains. However, diffusion of CAZ and IPM was significantly faster through strain M6 biofilm in comparison with strain 377 biofilm. The viabilities of strain 377 biofilm were significantly higher than those observed with strain M6 for all antibiotics challenged at 4 h, suggesting that the biofilm-forming capacity may be involved in antibiotic susceptibilities in B. pseudomallei. These results re-emphasise the importance of biofilm for antibiotic resistance in B. pseudomallei.


Protective effects of Salidroside on spermatogenesis in streptozotocin induced type-1 diabetic male mice by inhibiting oxidative stress mediated blood-testis barrier damage.
Spermatogenic dysfunction is one of the major secondary complications of male diabetes. Salidroside (SAL) is the important active ingredients isolated from Herba Cistanche, which exhibits numerous pharmacological activities such as antioxidant, anti-diabetic, and anti-inflammatory effects. The present study was designed to determine whether SAL contributes to the recovery from spermatogenic dysfunction in streptozotocin (STZ) induced type-1 diabetic mice. SAL (25, 50, or 100 mg/kg) and Clomiphene citrate (CC, 5 mg/kg) were orally administered to male type-1 diabetic mice for 10 weeks. Testis tissues were collected for histopathological and biochemical analysis. Moreover, reproductive organ weight, sperm parameters, and testicular cell DNA damage were estimated. The results revealed that SAL significantly improved the weight of the reproductive organs, sperm parameters and testicular morphology to different degrees in type-1 diabetic mice. Furthermore, reactive oxygen species (ROS) and malondialdehyde (MDA) levels were significantly reduced, and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), markedly increased in the testicular tissue after SAL treatment. In addition, our data also showed a marked downregulation the fluorescence expressions of p38 MAPK phosphorylation and upregulation the protein expressions of ZO-1, Occludin, Claudin-11 and N-cadherin after SAL administration (100 mg/kg) compared with the type-1 diabetic group. In conclusion, these results demonstrated that SAL exerts protective effects on type-1 diabetes-induced male spermatogenic dysfunction, which is likely mediated by inhibiting oxidative stress-mediated blood testis barrier damage.


Large-Scale Comparative Analyses of Tick Genomes Elucidate Their Genetic Diversity and Vector Capacities.
Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.


Inhibition of IgA1 proteinases from Neisseria gonorrhoeae and Hemophilus influenzae by peptide prolyl boronic acids.
The alpha-aminoboronic acid analog of proline has been synthesized and incorporated into a number of peptides as the COOH-terminal residue. These peptide prolyl boronic acids are potent inhibitors of both the type 1 and type 2 IgA proteinases from Neisseria gonorrhoeae and Hemophilus influenzae, but not of the functionally similar IgA proteinase from Streptococcus sanguis. The best inhibitors synthesized thus far have Ki values in the nanomolar range (4.0 to 60 nM). These results indicate that the N. gonorrhoeae and the H. influenzae enzymes belong to the serine protease family of proteolytic enzymes while that from S. sanguis does not. As a group, the IgA proteinases have been noted for their remarkable specificity; thus, the peptide prolyl boronic acids reported here are the first small synthetic molecules to exhibit a relatively high affinity for the active site of an IgA proteinase and are therefore the first to yield some insight into the active site structure and specificity requirements of these enzymes.


Impact of home- and community-based services in the long-term care insurance system on outcomes of patients with acute heart failure: Insights from the Kitakawachi Clinical Background and Outcome of Heart Failure Registry.
In Japan, the long-term care insurance (LTCI) system is important for elderly people living at home; however, no clinical studies have revealed a relationship between home- or community-based services and outcomes in patients with acute heart failure (AHF). This was a prospective multicenter cohort study of patients with AHF enrolled between April 2015 and August 2017. Patients aged ≥65 years with LTCI were divided into those receiving home- and community-based services (service users) and without home and community-based services (service non-users). The endpoint was defined as a composite endpoint, which included all-cause mortality and hospitalization for heart failure after discharge. Subgroup analyses were performed for elderly patients (<85 years) or super-elderly patients (≥85 years). The study participants were eligible for LTCI two times more than community-dwelling people were. At the 1-year follow-up period, the rate of the composite endpoint showed no significant difference between service users and service non-users among all patients or super-elderly patients. However, in elderly patients, the rate of the composite endpoint was significantly lower among service users than service non-users. The difference was independently maintained even after adjustments for differences in comorbidities or in social backgrounds (adjusted hazard ratio 0.62; 95% confidence interval 0.38-0.99, and adjusted hazard ratio 0.57; 95% confidence interval 0.35-0.90, respectively). In this study, adverse events following discharge of patients with AHF who used home- and community-based services were prevented only in elderly patients, not in super-elderly patients. Geriatr Gerontol Int 2020; 20: 967-973.


Circulating miR-3197 and miR-2116-5p as novel biomarkers for diabetic retinopathy.
Diabetic retinopathy (DR) is the leading cause of vision loss among older adults. The goal of this case-control study was to identify circulating miRNAs for the diagnosis of DR. The miRNeasy Serum/Plasma Kit was used to extract serum miRNAs. The μParaflo™ MicroRNA microarray was used to detect the expression levels of the miRNAs. The miRWalk algorithm was applied to predict the target genes of the miRNAs, which were further confirmed by the dual luciferase reporter gene system in HEK293T cells. A microarray was performed between 5 DR cases and 5 age-, sex-, body mass index-, and duration of diabetes-matched type 2 diabetic (T2DM) controls. The quantitative reverse transcription polymerase chain reaction technique was used to validate the differentially expressed circulating miRNAs in 45 DR cases and 45 well-matched controls. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the circulating miRNAs as diagnostic biomarkers for DR. Our microarray analysis screened out miR-2116-5p and miR-3197 as significantly up-regulated in DR cases compared with the controls. Furthermore, two miRNAs were validated in the 45 DR cases and 45 controls. The ROC analysis suggested that both miR-3197 and miR-2116-5p distinguished DR cases from controls. An additional dual-luciferase reporter gene assay confirmed that notch homolog 2 (NOTCH2) was the target gene of miR-2116-5p. Both miR-3197 and miR-2116-5p were identified as promising diagnostic biomarkers for DR. Future research is still needed to explore the molecular mechanisms of miR-3197 and miR-2116-5p in the pathogenesis of DR.


Gene expression patterns in response to pathogen challenge and interaction with hemolin suggest that the Yippee protein of Antheraea pernyi is involved in the innate immune response.
Yippee was first identified as a protein that physically interacts with the Hemolin protein of Hyalophora cecropia. In this study, we identified a gene with a 366bp open reading frame (ORF) that encodes a 121 amino acid protein containing a conserved Yippee domain. We named this gene Ap-Yippee (Yippee gene from Antheraea pernyi), and investigated the role of the protein in the host immune response. A recombinant Ap-Yippee protein was expressed in Escherichia coli cells, and polyclonal antibodies were produced against the recombinant protein. Real-time PCR and a Western blot analysis revealed that Ap-Yippee is expressed in the hemocytes, Malpighian tubules, midgut, silk gland, epidermis, and fat bodies of A. pernyi, with the highest expression level observed in Malpighian tubules. The fifth instar larvae of A. pernyi were challenged by injecting them with nucleopolyhedrovirus (AP-NPV), the Gram-negative bacterium E. coli, the Gram-positive bacterium Micrococcus luteus, or the entomopathogenic fungus, Beauveria bassiana. These challenges with diverse pathogens resulted in differential expression patterns of the protein. A knockdown of the Ap-Yippee gene by small interfering RNA (siRNA) transfection had a significant influence on the expression of the hemolin in the pupae which was confirmed by qRT-PCR and Western blot. Furthermore, a possible protein-protein interaction between Ap-Yippee and Hemolin was explored by Far-Western blotting. Therefore, our data suggest that the Ap-Yippee protein is involved in a pathway that regulates the immune response of insects.


Categories of foot at risk in patients of diabetes at a tertiary care center: Insights into need for foot care.
Diabetic foot ulcers and amputations are preventable. Aim of this study was to determine the distribution of categories of foot at risk in patients with diabetes, attending a tertiary care hospital and factors that affect it. Detail history and examination including neurological and vascular assessment were performed in 100 patients with diabetes attending a Tertiary Care Hospital. Foot at risk was classified according to the task force of foot care interest Group of American Diabetes Association. Category of foot at risk was correlated with demographic and clinical features. Fifty-two percent patients had foot at risk-category 1 and 2. Loss of protective sensation (LOPS) was present in 33% (category 1). Peripheral arterial disease (PAD) was present in 19% (category 2). Both LOPS and PAD were present in 10% patients. 95% had never received foot care advice by health professionals, let alone prescriptive footwear or vascular consultation. This study brings forth that foot at risk of ulcer is rampant in patients with diabetes. There are lacunae in diabetic foot care at all levels of care. With the increase in diabetes, cost effective steps are required to improve foot care among diabetes in India. Considering the demographic profile of patients in our study, growing number of patients with diabetes, lack of time and staff allocated for foot care in our setup, audiovisual aids seems a good option to spread foot care awareness among diabetes.


Training program using a traction device improves trainees' learning curve of colorectal endoscopic submucosal dissection.
Colorectal endoscopic submucosal dissection (ESD) requires advanced endoscopic skill. For safer and more reliable ESD implementation, various traction devices have been developed in recent years. The purpose of this research was to evaluate whether an ESD training program using a traction device (TD) would contribute to the improvement of trainees' skill acquisition. The differences in treatment outcomes and learning curves by the training program were compared before and after the introduction of TD (control group: January 2014 to March 2016; TD group: April 2016 to June 2018). A total of 316 patients were included in the analysis (TD group: 202 cases; control group: 114 cases). The number of cases required to achieve proficiency in ESD techniques was 10 in the TD group and 21 in the control group. Compared to the control group, the TD group had a significant advantage in ESD self-completion rate (73.8% vs. 58.8%), dissection speed (19.5 mm2/min vs. 15.9 mm2/min), en bloc resection rate (100% vs. 90%), and R0 resection rate (96% vs. 83%). The rate of colorectal ESD self-completion by trainees improved immediately after the start of the training program using a traction device compared to the conventional method, and the dissection speed tended to increase linearly with ESD experience. We believe that ESD training using a traction device will help ESD techniques to be performed safely and reliably among trainees.


Ultrasonography of the popliteal fossa and lower extremities.
In this article, the numerous proven applications of diagnostic ultrasound to the assessment of disease processes affecting the popliteal fossa and lower extremities have been discussed. Popliteal cysts and aneurysms, hematomas, cellulitis, abscesses, soft tissue neoplasms, and other space-occupying fluid collections are readily identified using this technique. In addition, post-traumatic and inflammatory disorders affecting tendons, synovial thickening and effusion, derangement of articular cartilage, meniscal tears, and alterations in soft tissue thickness as well as foreign bodies are amenable to detection by sonography. With future technologic improvements in transducer design and computerized image reconstruction, diagnostic capabilities of this method in the lower extremities should continue to expand.


Genetic polymorphisms of viral infection-associated Toll-like receptors in Chinese population.
Toll-like receptors (TLRs) play a pivotal role in an innate immunity system, which controls inflammation responses and further instructs development of adaptive immunity. We enrolled 250 Han Chinese in Taiwan screening for the single nucleotide polymorphisms (SNPs) in TLRs associated with viral infection, including TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9. The 6 SNPs not hitherto identified in Chinese populations, including TLR3 1377 C>T, TLR3 -7 C>A, TLR7 Gln11Leu, TLR7 IVS1+1817 G>T, TLR8 Met1Val, and TLR8 -129 G>C, had minor allele frequencies of 38%, 23%, 22.3%, 3%, 16.0%, and 16.0%, respectively. The frequencies of 2 common SNPs, TLR9, -1486 T>C and 2848 G>A, were 28% and 44%, respectively. As compared with other ethnic populations, Chinese displayed an opposite allele frequency of TLR8 Met1Val and TLR8 -129 G>C to Caucasians and African Americans. In addition, TLR2 Arg677Try, TLR2 Arg753Gln, TLR4 Asp299Gly, and TLR4 Thr399Ile that were apparent in approximately 10% of Caucasians were not detected in Chinese. In conclusion, obvious ethnic differences in TLR polymorphisms may in part reflect the ethnic diversity of host viral susceptibility.


Large-scale brain network abnormalities in Huntington's disease revealed by structural covariance.
Huntington's disease (HD) is a progressive neurodegenerative disorder that can be diagnosed with certainty decades before symptom onset. Studies using structural MRI have identified grey matter (GM) loss predominantly in the striatum, but also involving various cortical areas. So far, voxel-based morphometric studies have examined each brain region in isolation and are thus unable to assess the changes in the interrelation of brain regions. Here, we examined the structural covariance in GM volumes in pre-specified motor, working memory, cognitive flexibility, and social-affective networks in 99 patients with manifest HD (mHD), 106 presymptomatic gene mutation carriers (pre-HD), and 108 healthy controls (HC). After correction for global differences in brain volume, we found that increased GM volume in one region was associated with increased GM volume in another. When statistically comparing the groups, no differences between HC and pre-HD were observed, but increased positive correlations were evident for mHD, relative to pre-HD and HC. These findings could be explained by a HD-related neuronal loss heterogeneously affecting the examined network at the pre-HD stage, which starts to dominate structural covariance globally at the manifest stage. Follow-up analyses identified structural connections between frontoparietal motor regions to be linearly modified by disease burden score (DBS). Moderator effects of disease load burden became significant at a DBS level typically associated with the onset of unequivocal HD motor signs. Together with existing findings from functional connectivity analyses, our data indicates a critical role of these frontoparietal regions for the onset of HD motor signs.


Hip Arthroscopy for Femoroacetabular Impingement Syndrome in Adolescents Provides Clinically Significant Outcome Benefit at Minimum 5-Year Follow-Up.
To report the rates of achieving clinically significant outcomes as defined by the minimal clinically important difference (MCID), patient acceptable symptomatic state (PASS), or substantial clinical benefit (SCB) in adolescent patients and the rates of clinical failure 5 years after undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS). Data from consecutive adolescent patients (defined by the American Academy of Pediatrics as age 11 to 21 years) who underwent primary hip arthroscopy with routine capsular closure for the treatment of FAIS between January 2012 and January 2015 by a single, fellowship-trained surgeon was collected. Baseline data, clinical outcomes including Hip Outcome Score (HOS)-Activities of Daily Living, HOS-Sports Subscale, modified Harris hip score, international Hip Outcome Tool, and clinical failure rates were recorded at 5 years after operative. Clinical failure was defined by revision hip arthroscopy or conversion to total hip arthroplasty. Clinically significant outcomes was defined as achieving MCID, PASS, or SCB on at least 1 hip-specific outcome measure. Of the 139 eligible patients, a total of 85 (60.4%) patients (85 hips) were included in the final analysis, with an age and body mass index average of 17.6 ± 2.5 years (range 13-21) and 22.3 ± 3.1 kg/m2, respectively. The majority of the patients were female (80.6%) and participated in sports (76.2%). There was statistically significant difference between preoperative and postoperative score averages across every reported outcome (P < .001). At 5 years, 88.4%, 67.6%, and 64.9% reached at least 1 threshold for achieving MCID, PASS, and SCB, respectively, whereas 89.2% achieved at least one of the meaningful outcome thresholds. Last, 2 patients (2.4%) failed clinically, with both undergoing revision (2.4%) because of continued pain. There were no conversions to total hip arthroplasty. This study demonstrated that a large majority (89.2%) of adolescent patients undergoing primary arthroscopic treatment for symptomatic FAIS achieved meaningful clinically significant outcomes. Furthermore, only 2.4% of patients failed clinically, requiring revision hip arthroscopy because of continued pain. IV, Retrospective Case Series.


CRISPR-Cas9-based genome-wide screening identified novel targets for treating sorafenib-resistant hepatocellular carcinoma: a cross-talk between FGF21 and the NRF2 pathway.
The treatment of hepatocellular carcinoma (HCC) has been dominated by multikinase inhibitors for more than a decade. However, drug resistance can severely restrict the efficacy of these drugs. Using CRISPR/CAS9 genome library screening, we evaluated Kelch-like ECH-associated protein 1 (KEAP1) as a key regulator of sorafenib's susceptibility in HCC. We also investigated whether KEAP1's knockdown can stabilize nuclear factor (erythroid-derived 2)-like 2 (NRF2) protein levels that led to sorafenib's resistance, including an NRF2 inhibitor that can synergize with sorafenib to abolish HCC's growth in vitro and in vivo. Furthermore, we clarified that fibroblast growth factor 21 (FGF21) is an important downstream regulator of NRF2 in HCC. Intriguingly, we observed that FGF21 bound to NRF2 through the C-terminus of FGF21, thereby stabilizing NRF2 by reducing its ubiquitination and generating a positive feedback loop in sorafenib-resistant HCC. These findings, therefore, propose that targeting FGF21 is a promising strategy to combat HCC sorafenib's resistance.


Water-Soluble, Biocompatible Polyphosphazenes with Controllable and pH-Promoted Degradation Behavior.
The synthesis of a series of novel, water-soluble poly(organophosphazenes) prepared via living cationic polymerization is presented. The degradation profiles of the polyphosphazenes prepared are analyzed by GPC, 31P NMR spectroscopy, and UV-Vis spectroscopy in aqueous media and show tunable degradation rates ranging from days to months, adjusted by subtle changes to the chemical structure of the polyphosphazene. Furthermore, it is observed that these polymers demonstrate a pH-promoted hydrolytic degradation behavior, with a remarkably faster rate of degradation at lower pH values. These degradable, water soluble polymers with controlled molecular weights and structures could be of significant interest for use in aqueous biomedical applications, such as polymer therapeutics, in which biological clearance is a requirement and in this context cell viability tests are described which show the non-toxic nature of the polymers as well as their degradation intermediates and products.


Risk factors for pre-operative functional deterioration in children with lipomyelomeningocele.
To characterize the temporal profile of pre-operative deterioration in children with lipomyelomeningocele (LMMC) including those with congenital deficits and identify risk factors for clinical worsening. Records of 87 children who underwent surgery for LMMC were retrospectively reviewed to study the temporal profile of pre-operative deterioration, defined by the onset of new neurological dysfunction or progression of a pre-existing deficit. Preoperative magnetic resonance imaging (MRI) studies were examined to identify radiological features associated with deterioration. In children with extra-spinal placodes, the angle subtended by the terminal placode with the cord at the level of the laminar-fascial defect ("J sign") was assessed. Pre-operative deterioration in function was seen in 37 children (43%), occurring at a median age of 36 months and was more frequent in children without congenital deficits (54% versus 27%; p = 0.016). On Cox regression analysis, extra-spinal location of the placode (p = 0.003) and presence of a congenital deficit (p = 0.009) were positively and negatively associated with deterioration respectively. On Kaplan-Meier analysis, the median deterioration-free survival time was 72 months and was positively associated with presence of congenital deficit (p = 0.026) and negatively associated with presence of an extra-spinal placode (p < 0.001) or a meningocele sac (p = 0.001). Extra-spinal location of the neural placode was associated with higher risk of clinical deterioration in children with LMMC, whereas the presence of a congenital deficit conferred a decreased risk. Risk stratification based on clinical and radiological features can be used to guide decisions regarding early prophylactic surgery in children with LMMC.


[Emergency management of thoracic trauma].
Thoracic injuries are a major cause of mortality during the "golden hour" of trauma. Many patients with chest trauma die after reaching the hospital. Less than 10% of all blunt thoracic injuries require a thoracotomy, and many potentially life-threatening conditions can be relieved by simple procedures, such as chest tube insertion.Thus, many cases of traumatic deaths due to chest injury may be prevented by prompt diagnosis and a standardized therapeutic approach in the emergency room. A high index of suspicion for lethal injury patterns, based on the mechanism of trauma and the clinical presentation, is a crucial prerequisite for an adequate initial assessment and management of patients with chest trauma. The worldwide implementation of standardized diagnostic and therapeutic guidelines, such as the "Advanced Trauma Life Support" (ATLS) protocol, has led to a significant reduction of early deaths attributed to thoracic injuries.


Leptin and the central control of feeding behavior.
The discovery of leptin by Friedman and coll. in 1995 was a major step forward in our comprehensive view of energy homeostasis. Since the original paper, a tremendous amount of work has been performed in laboratories all over the world. Many recent reviews have described this work in details. In the present review, we focus on the role of leptin on food intake. It is accepted by most authors working in this field that the control of food intake can be divided in two closely-related system: the homeostatic system and the hedonic system. Leptin has been shown to act on both systems.


The effects of enteral stimulation on gallbladder bile during total parenteral nutrition in the neonatal piglet.
The neonatal piglet is a satisfactory model for the human neonate requiring total parenteral nutrition (TPN). Bile status and subsequent liver and gallbladder dysfunction have long been documented as serious complications of long-term TPN. The purpose of this study was to determine whether small amounts of enteral formula during TPN will maintain normal bile appearance and composition. Thirty-one Hanford miniswine, 3 to 6 days old underwent surgery for the placement of central venous catheters. Two days postoperatively, the animals were separated into three groups, according to dietary regimens. Group 1 (n = 10), the control group, received pig formula (SPF-lac) orally (200 cal/kg/d); group 2 (n = 11), was maintained on TPN (180 cal/kg/d) with an enteral supplement of SPF-lac (20 cal/kg/d); group 3 (n = 10), was maintained on TPN only (200 cal/kg/d). The TPN formula consisted of 35 g/kg/d of glucose, 10 g/kg/d of protein, and 3 g/kg/d of lipid. The animals were maintained on these diets for 6 weeks. At necropsy, gallbladder with bile was weighed and bile volume and appearance was recorded. Chemical analyses was performed on 26 bile samples. Gallbladder weight was significantly decreased in groups 2 and 3 compared with group 1 (P less than .0003, P less than .033, respectively, using Students t test with Bonferoni adjustment). Volume was significantly decreased only in group 2 (P less than .003). Group differentiation in relation to bile appearance was determined by the presence or absence of either bile sludge or crystals.(ABSTRACT TRUNCATED AT 250 WORDS)


A cascade of gene action controlling heart asymmetry and torsion in embryonic development.
Lateralized looping of the heart tube, with associated torsion of the embryo axis, is the first structural sign of the consistent left-right asymmetrical organization that characterizes all vertebrate embryos. Rare failures or reversals of this asymmetry in humans lead to clinically important syndromes of malformation in heart and great blood vessels. Recently, elements of the genetic control sequence underlying this left-right aspect of development have been uncovered. The normal sequence of transmission for asymmetry information can now be traced to a point close to the actual execution of right-hand looping in the heart tube, with the hope that the further sequence of gene activity, within the heart itself and directing these events, may soon be uncovered.


Population burst propagation across interacting areas of the brain.
For many perceptual and behavioral tasks, a prominent feature of neural spike trains involves high firing rates across relatively short intervals of time. We call these events "population bursts." Because during a population burst information is, presumably, transmitted from one part of the brain to another, burst timing should reveal activity related to the flow of information across neural circuits. We developed a statistical method (based on a point process model) of determining, accurately, the time of the maximum (peak) population firing rate on a trial-by-trial basis and used it to characterize burst propagation across areas. We then examined the tendency of peak firing rates in distinct brain areas to shift earlier or later in time, together, across repeated trials, and found this trial-to-trial coupling of peak times to be a sensitive indicator of interaction across populations. In the data we examined, from the Allen Brain Observatory, we found many very strong correlations (95% confidence intervals above 0.75) in cases where standard methods were unable to demonstrate cross-area correlation. The statistical model introduced cross-area covariation only through population-level trial-dependent time shifts and gain constants (values of which were learned from the data), yet it provided very good fits to data histograms, including histograms of spike count correlations within and across visual areas. Our results demonstrate the utility of carefully assessing timing and propagation, across brain regions, of transient bursts in neural population activity, based on multiple spike train recordings.NEW & NOTEWORTHY We developed a novel statistical method for identifying coordinated propagation of activity across populations of spiking neurons, with high temporal accuracy. Using simultaneous recordings from three visual areas we document precise timing relationships on a trial-by-trial basis, and we show how previously existing techniques can fail to discover coordinated activity in cases where the new approach finds very strong cross-area correlation.


Enhanced function and quality of life following 5 months of exercise therapy for patients with irreparable rotator cuff tears - an intervention study.
Rotator cuff rupture is associated with dysfunction, pain and muscular weakness related to the upper extremity. Some evidence exists to support the beneficial effect of exercises but there is lack of evidence of which exercises imply the best effect and how physiotherapy should be administered. Therefore, the purpose of this study was to examine the effect of a neuromuscular exercise program for patients with irreparable rotator cuff rupture. Based on sample-size calculations thirty patients with chronic irreparable rotator cuff tears (of at least m. supraspinatus and m. infraspinatus) was consecutively included. Twenty-four patients completed the five months training to restore function with focus on centering the humeral head in the glenoid cavity trough strengthening m. deltoideus anterior and m. teres minor. The primary outcome measure was Oxford Shoulder Score which was completed at baseline, 3 and 5 months follow-up. One-way, repeated-measure ANOVA was used if data was normally distributed. Secondary outcome measures included EQ-5D, range of motion, strength and muscle activity. Paired t-test and Wilcoxon Signed Ranks Test was used to the appropriate outcomes. Improvements was seen for both primary and secondary outcomes from baseline to follow-up. Oxford Shoulder Score improved from 25.6 (SD 8.1) at baseline to 33.8 (SD 8.7) at 3 months (p = 0.004) and 37.2 (SD 8.2) at five months (p < 0.001). Range of motion in abduction significantly increased by 34.4° (95 % CI: 11.6-57.2). Strength measured in flexion 45, flexion 90 and abduction also significantly increased at 5 months by 10.2 (95 % CI: 0.8-19.6), 7.0 (95 % CI: 0.0-14.0) and 12.3 (95 % CI: 3.4-21.3) respectively. The remaining outcomes for range of motion and strengths only showed small and non-significant changes. Furthermore patients reported higher levels of quality of life and reduced level of pain after five months. Following a five months exercise protocol patients with irreparable rotator cuff tears showed increased function in their symptomatic shoulder, reduced pain and increased quality of life. This study therefore supports the use of exercise therapy in patients with irreparable rotator cuff rupture. This study is approved by The National Committee on Health Research Ethics (N-20120040) and registered retrospectively at ClinicalTrials.gov in April 2016 ( NCT02740946 ).


Neurotuberculosis: Control of Steroid-Refractory Paradoxical Inflammatory Reaction With Ruxolitinib.
Paradoxical inflammatory reactions associated with treatment of neurotuberculosis can lead to severe morbidity and mortality and may not be controlled by steroids alone. We report the use of the Janus kinase inhibitor ruxolitinib to treat a steroid-refractory neurotuberculosis paradoxical reaction.


Deferred cord clamping and cord milking: Certainty and quality of the evidence in meta-analyses, and systematic reviews of randomized control trials, guidelines, and implementation studies.
Deferred1 cord clamping (DCC) saves lives, so why is it not implemented more routinely? Despite neonatal benefits, DCC is under-utilized, particularly in preterm births. Umbilical cord milking (UCM) also improves some outcomes for preterm infants such as decreasing the need for transfusions. At term, DCC and UCM improve hematological indices. The objective of this chapter is to examine the quality of evidence for both preterm and term DCC (and UCM), clinical practice guidelines and implementation issues. Key evidence, primarily from network meta-analyses, meta-analyses and systematic reviews on both preterm and term DCC (and UCM) from randomized clinical trials, clinical practice guidelines and implementation studies, are summarized through a lens of the certainty and quality of the evidence. Regarding the certainty of evidence, for network meta-analysis the Confidence in Network Meta-analysis tool was used, and for meta-analyses the Cochrane Risk of Bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used. Guideline quality was appraised with two tools: Appraisal of Guidelines for REsearch & Evaluation II (AGREE II) and AGREE-Recommendation EXcellence (AGREE-REX). Implementation study quality was evaluated using The Mixed Method Appraisal tool. In a network meta-analysis of 56 RCTs of cord management strategies, DCC reduced the odds of mortality in preterm infants by 30% compared to immediate cord clamping (ICC), including in the subgroup of infants born before 33 weeks', both with a moderate confidence assessment using the Confidence in Network Meta-analysis tool. DCC reduced the odds of any intraventricular hemorrhage (IVH) by 30%, and the odds of red blood cell transfusion by more than 50%, both with high ratings on the Confidence in Network Meta-analysis. Umbilical Cord Milking (UCM) did not reduce mortality compared to ICC. In contrast to the benefits shown in preterm birth with DCC, a systematic review showed that at term, there were no mortality benefits and few benefits at all except for improved hematological indices. A systematic review of clinical practice guidelines demonstrated that all of them endorsed DCC for uncompromised preterm infants, and 11 more cautiously noted that cord milking might be considered when DCC was not feasible. However, only half (49%) of the recommendations in the guidelines on the optimal duration of DCC were supported by high-quality evidence per AGREE-II and AGREE-REX. Fewer than one in 10 statements (8%) cited a mortality benefit with DCC for preterm infants. Regarding the uptake of DCC, a systematic review of 18 studies on facilitators and barriers to implementation found that almost all (12 of the 14 studies) focused on strategies such as protocols, policy, or toolkits; additionally, 8 of 14 studies used didactic teaching sessions. Only 8 of 18 studies scored high on all four domains of the Mixed Method Appraisal tool. Compared to ICC, DCC in preterm infants conferred significant benefits for mortality, IVH and red blood cell transfusion, with confidence ratings of moderate (mortality) or high. Although guidelines worldwide encouraged preterm (and term) DCC, the quality of the clinical practice guidelines had room for improvement; only half of the recommendations on the optimal duration of preterm DCC were supported by high-quality evidence. Most guidelines did not mention a mortality benefit with preterm DCC and lacked details on practical aspects of implementation. Among implementation studies, which have focused mainly on protocols, policies, toolkits or didactic teaching, quality also demonstrated an opportunity for improvement.


Genetic influence on prolonged gestation: a population-based Danish twin study.
The purpose of this study was to test a possible genetic component to prolonged gestation. The gestational duration of single, first pregnancies by both female and male twins was obtained by linking the Danish Twin Registry, The Danish Civil Registration System, and the Danish Medical Birth Register. A total of 2588 same-sex twin pairs of whom both cotwins became parents during 1978 to 1996 were identified. The concordance rate for female twin pairs for a gestation of > or =41 weeks and > or =42 weeks was higher for monozygotic twin pairs than for dizygotic twin pairs, which indicates genetic effects. Biometric modeling suggested that genetic factors account for 23% to 30% of the liability to prolonged gestation. The difference in concordance rate between monozygotic and dizygotic male twin pairs was small, and the best fitting model indicated no genetic factors. Maternal genes influence prolonged gestation. However, a substantial paternal genetic influence through the fetus was not found.


Hemophagocytic syndrome after liver transplantation: report of two cases.
We report two cases of hemophagocytic syndrome (HPS), a rare but fatal complication after living-donor liver transplantation (LDLT). Despite their recovery from pancytopenia following treatment with steroid pulse therapy, granulocyte stimulating factor, and intravenous γ-globulin, both patients died. The outcomes reported in cases published in English are devastating, with only 4 survivors among the total 14 patients including ours. Pancytopenia is frequently recognized postoperatively in liver transplant recipients, although its cause is difficult to establish. When pancytopenia accompanying persistent high fever is recognized in LDLT recipients, HPS should be suspected and bone marrow aspiration performed as promptly as possible because of the poor prognosis of this syndrome. There is still no optimal treatment for HPS after liver transplantation.


Genome-wide screening of novel RT-qPCR reference genes for study of GLRaV-3 infection in wine grapes and refinement of an RNA isolation protocol for grape berries.
Grapevine, as an essential fruit crop with high economic values, has been the focus of molecular studies in diverse areas. Two challenges exist in the grapevine research field: (i) the lack of a rapid, user-friendly and effective RNA isolation protocol for mature dark-skinned berries and, (ii) the lack of validated reference genes that are stable for quantification of gene expression across desired experimental conditions. Successful isolation of RNA with sufficient yield and quality is essential for downstream analyses involving nucleic acids. However, ripe berries of dark-skinned grape cultivars are notoriously challenging in RNA isolation due to high contents of polyphenolics, polysaccharides, RNase and water. We have optimized an RNA isolation protocol through modulating two factors at the lysis step that could impact results of RNA isolation - 2-ME concentration and berry mass. By finding the optimal combination among the two factors, our refined protocol was highly effective in isolating total RNA with high yield and quality from whole mature berries of an array of dark-skinned wine grape cultivars. Our protocol takes a much shorter time to complete, is highly effective, and eliminates the requirement for hazardous organic solvents. We have also shown that the resulting RNA preps were suitable for multiple downstream analyses, including the detection of viruses and amplification of grapevine genes using reverse transcription-polymerase chain reaction (RT-PCR), gene expression analysis via quantitative reverse transcription PCR (RT-qPCR), and RNA Sequencing (RNA-Seq). By using RNA-Seq data derived from Cabernet Franc, we have identified seven novel reference gene candidates (CYSP, NDUFS8, YLS8, EIF5A2, Gluc, GDT1, and EF-Hand) with stable expression across two tissue types, three developmental stages and status of infection with grapevine leafroll-associated virus 3 (GLRaV-3). We evaluated the stability of these candidate genes together with two conventional reference genes (actin and NAD5) using geNorm, NormFinder and BestKeeper. We found that the novel reference gene candidates outperformed both actin and NAD5. The three most stable reference genes were CYSP, NDUFS8 and YSL8, whereas actin and NAD5 were among the least stable. We further tested if there would be a difference in RT-qPCR quantification results when the most stable (CYSP) and the least stable (actin and NAD5) genes were used for normalization. We concluded that both actin and NAD5 led to erroneous RT-qPCR results in determining the statistical significance and fold-change values of gene expressional change. We have formulated a rapid, safe and highly effective protocol for isolating RNA from recalcitrant berry tissue of wine grapes. The resulting RNA is of high quality and suitable for RT-qPCR and RNA-Seq. We have identified and validated a set of novel reference genes based on RNA-Seq dataset. We have shown that these new reference genes are superior over actin and NAD5, two of the conventional reference genes commonly used in early studies.


Dataset describing ethanol and 1,2-propanediol production by a stenothermal moderately thermophilic anaerobe, Clostridium strain AK1.
The dataset details the fermentation of D-glucose, L-rhamnose, and L-fucose and their end-product formation by the moderate thermophile Clostridium strain AK1 (DSM 18778) as related to the work described in "Propanediol from L-rhamnose using the moderately thermophilic Clostridium strain AK1" [1]. The influence of culture conditions on end product formation from D-glucose and L-rhamnose by AK1 was investigated in batch culture. Strain AK1 was cultivated at initial substrate concentrations varying from 0 to 60 mM and initial pH values varying from 4.5 to 8.5. Additionally different cultivation temperatures (30-65 °C), the influence of liquid-gas phase ratio as well as different phosphate concentrations on growth were investigated.


In Vitro Element Bioavailability Studies of Some Underutilized Seeds in Southeast Nigeria.
Elemental and antinutritional compositions of three underutilized seeds (Mucuna sloanei, Brachystegia eurycoma and Detarium microcarpum) were analysed to elucidate their safety and wholesomeness as human food supplements or condiments using standard analytical methods. Results showed that there were significant differences in the concentration levels of the elements and the antinutrient contents of the seeds. The toxic element concentration levels clearly indicated that they exhibited acceptable values when compared with the recommended standards. There existed correlation between the contents of potassium, manganese, selenium and lead of the samples; calcium had inverse relationship with the oxalate contents, while lead and manganese had perfect association in all the samples. The results of elemental ratios showed synergistic interactions with exception of iron to zinc ratio in all the seeds. Element bioavailability in the presence of oxalate and phytate were all in tandem with the standard values. The results further revealed that zinc in all the seeds and selenium in Mucuna sloanei and Brachystegia eurycoma were overloaded in the samples, while the elemental safety index values for the other elements indicated that the seeds were safe. Overall, the findings of this study have strongly confirmed the nutritional potentials of these seeds and its safety and wholesomeness as human food condiments.


Aflatoxin B1, zearalenone and deoxynivalenol production on irradiated corn kernels: Influence of inoculum size.
The influence of inoculum size on aflatoxin B1 (AFB1), zearalenone (ZEN) and deoxynivalenol (DON) production was examined on irradiated corn kernels.Spore concentrations were determined in serial dilutions and adjusted to 10,10(2),10(3),10(5) and 10(6) spores/ml. Aflatoxin B1 production was dependent on the inoculum size. The high levels of aflatoxin B1 produced byA. parasiticus (21 and 30 mg/kg) were obtained with 10(2) and 10(3) spores/ml after 35 and 20 days incubation. There was no spore concentration influence on zearalenone and deoxynivalenol production after 10, 20 and 35 days incubation. At 28°C and 0.97 water activity (aw), the mean levels of zearalenone production were 382, 267 and 520 µg/kg and the mean levels on deoxynivalenol production were 697,465 and 782 µg/kg.


Graphene nanosheets-supported Ag nanoparticles for ultrasensitive detection of TNT by surface-enhanced Raman spectroscopy.
Sensitive and selective detection of 2,4,6-trinitrotoluene (TNT) has attracted considerable attention due to the wide applications of TNT as explosive material. Many efforts have been made to develop various sensors for detecting TNT in recent years. We herein report a novel sensor based on p-aminothiophenol (PATP) functionalized silver nanoparticles supported on graphene nanosheets (Ag/GNs), which was found to be a kind of effective chemosensor for the ultratrace detection of TNT by using surface enhanced Raman scattering (SERS). In the present hybrid material, PATP is paired together to form a corresponding azo compound p, p'-dimercaptoazobenzene (DMAB) and thus can be used as a model Raman probe. The π-donor-acceptor interaction between π-acceptor TNT and π-donor DMAB-Ag/GNs complex can effectively induce the "hot spots" for SERS. The intense spectral resonance from the DMAB-TNT-DMAB bridges formed between the Ag/GNs nanosheets could result in enhanced Raman signals of DMAB molecules with the presence of ultratrace TNT. SERS measurements demonstrated that TNT with concentration as low as 10(-11)M can be detected by using the present SERS platform. The present study not only provides a facile method for ultrasensitive and selective detection of TNT but also could develop a graphene-based SERS platform.


Fibrotic Matrix Induces Mesenchymal Transformation of Epithelial Cells in Oral Submucous Fibrosis.
Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant transformation of epithelial cells remains unknown. Herein, oral mucosa tissue from patients with OSF, OSF rat models, and their controls were used to observe the extracellular matrix changes and epithelial-mesenchymal transformation (EMT) in fibrotic lesions. Compared with controls, oral mucous tissues from patients with OSF showed an increased number of myofibroblasts, a decreased number of blood vessels, and increased type I and type III collagen levels. In addition, the oral mucous tissues from humans and OSF rats showed increased stiffness, accompanied by increased EMT activities of epithelial cells. The EMT activities of stiff construct-cultured epithelial cells were increased significantly by exogenous piezo-type mechanosensitive ion channel component 1 (Piezo1) activation, and decreased by yes-associated protein (YAP) inhibition. During ex vivo implantation, oral mucosal epithelial cells of the stiff group showed increased EMT activities and increased levels of Piezo1 and YAP compared with those in the sham and soft groups. These results indicate that increased stiffness of the fibrotic matrix in OSF led to increased proliferation and EMT of mucosal epithelial cells, in which the Piezo1-YAP signal transduction is important.


Combined phacoemulsification and viscogoniosynechialysis in patients with refractory acute angle-closure glaucoma.
To evaluate the effectiveness of phacoemulsification and viscogoniosynechialysis in managing refractory acute angle-closure glaucoma (ACG) unresponsive to laser iridotomy and medical therapy. Department of Ophthalmology, Khalili Hospital, Shiraz Medical University, Shiraz, Iran. Eleven patients with acute ACG who did not respond to standard therapy and who had peripheral anterior synechia (PAS) of 270 degrees or less had phacoemulsification and viscogoniosynechialysis. After phacoemulsification, the anterior chamber was deepened with an ophthalmic viscosurgical device, which was then injected near the angle without touching any ocular structure to release the PAS. Eleven patients with a mean age of 58.9 years were included over a mean follow-up of 7.8 months. Preoperatively, the mean intraocular pressure (IOP) was 39.4 mm Hg and the mean number of antiglaucoma medications, 3.8. Postoperatively, the mean IOP decreased to 13.4 mm Hg (P = .003) and the mean number of medications, to 0.4 (P = .002). The mean logMAR visual acuity improved from 0.94 to 0.55 (P = .007). In 8 eyes (72.8%), IOP was controlled without antiglaucoma therapy. Of patients whose IOP was controlled with medication, 1 was on 3 medications and the others on 1 medication. In all patients except the one whose IOP was controlled by 3 medications, the previously occluded trabecular meshwork was exposed over 360 degrees on gonioscopy. Combined phacoemulsification and viscogoniosynechialysis was an effective and safe treatment for the management of refractory acute ACG that was unresponsive to laser iridotomy and medical therapy.


Emelda's story: applying ethnographic insights to cultural assessment and cervical cancer control.
This article builds a bridge between cultural research and clinical practice by applying insights from an ethnographic study of cervical cancer in Iquitos, Peru, to a cervical cancer focused cultural assessment tool and teaching guide for use with immigrant patients. This application is grounded in Campinha-Bacote's model of cultural competency. Ethnographic research is recommended as a source of knowledge from which insights can be drawn to build assessment skill in cross-cultural clinical encounters-insights into asking the right questions.


The effect of dexamethasone therapy in prolonged pregnancy.
Fifty-six patients, chosen by random sampling from a total group of 120 post-term women, received dexamethasone (Decadron, "MSD" 2 mg 3 times a day for 4 days, the other 64 patients acting as controls. The evolution of uterine activity was evaluated using pelvic score (PS) and a modified low dosage oxytocin sensitivyt test (OST) before (T1) and after (T2) the treatment. During the interval from the second to the 6th day inclusive after T1 35 women of the dexamethasone group and 15 of the control group had a spontaneous onset of labour (SO) (0.001 less than P less than 0.01). Five patients in the dexamethasone group with primary rupture of membranes started labour spontaneously within 12 hours after membrane rupture, 7 patients in the control group with primary rupture of membranes received oxytocin as labour did not start within 24 hours. Excluding patients artifically induced, the mean interval from T1 to SO was 6.8 days in the control group and 5.2 days in the dexamethasone group (P less than 0.001). In both groups PS and the sum of Montevideo units (MU) during OST increased from T1 to T2, the increase was significantly greater in the dexamethasone group than in the control group. We found no correlation between the results of OST and the T1--SO interval. Dexamethasone, as used in this study, may promote labour in prolonged human pregnancy. Due to its low potency, it is not a substitute for oxytocin in the induction of labour. The lowered placento-fetal quotient in the dexamethasone group warrants further study of the effects of steroid hormone on placental function.


Advances in the treatment of intracapsular hip fractures in the elderly.
A review of recent advances in the treatment of intracapsular hip fractures in the elderly patient is offered to provide some guidelines on choosing the appropriate treatment for a given patient. Alternatives discussed include open reduction and internal fixation versus arthroplasty; unipolar versus bipolar hemiarthroplasty versus total hip arthroplasty; cemented versus cementlless prostheses; and a surgical approach. These recommendations are based upon a review of the substantial literature on the subject and the author's own experience. It is recommended that patients more than 60-years-old with a femoral neck fracture be treated in the following manner: Patients with undisplaced, stable fractures perform an ORIF, patients with displaced fractures, replace the head of the femur, the use of a Moore or Thompson prostheses should be relegated to the medically infirm, minimally ambulatory patient, modular unipolar or bipolar (cemented stem) hemiarthroplasty has the most reliable and predictable outcome in most patients, an uncemented modular hemiarthroplasty should be considered in patients with significant cardiovascular risk factors, THA perhaps recommended for the "active elderly patient". The use of large heads and meticulous capsular repair techniques will reduce the early dislocation rate while still allowing excellent long-term functional outcomes.


Mouse Model of Latent Cryptococcal Infection and Reactivation.
AbstractCryptococcus neoformans is an opportunistic fungal pathogen that frequently causes fatal meningoencephalitis in patients with impaired immune responses. This fungus, an intracellularly growing microbe, evades host immunity, leading to a latent infection (latent C. neoformans infection: LCNI), and cryptococcal disease is developed by its reactivation when host immunity is suppressed. Elucidation of the pathophysiology of LCNI is difficult due to the lack of mouse models. Here we show the established methods for LCNI and reactivation.


Single-dose pharmacokinetics of ofloxacin during continuous venovenous hemofiltration in critical care patients.
Ofloxacin is a quinolone administered to patients with severe infections. Pharmacokinetic data on ofloxacin in critically ill patients on renal replacement therapy are sparse and conflicting. Eight patients with anuric acute renal failure were administered 400 mg of ofloxacin intravenously. The pharmacokinetics of ofloxacin was analyzed during continuous venovenous hemofiltration (CVVH) with a high-flux polysulfone membrane. Serum and ultrafiltrate levels of ofloxacin were measured by means of high-performance liquid chromatography. Mean serum ofloxacin concentration peak was 5.5 +/- 0.7 mg/L. Elimination half-life, hemofiltration clearance, and total removal were 2.8 +/- 0.5 hours, 89.9 +/- 4.5 mL/min, and 76.9% +/- 7.1%, respectively. Ofloxacin is significantly and rapidly eliminated by CVVH with a high-flux polysulfone membrane.


Estimation of coronary artery movement using a non-rigid registration with global-local structure preservation.
At present, coronary artery disease (CAD) is the leading cause of death worldwide. Many studies have shown that CAD is strongly associated with the motion characteristics of the coronary arteries. Although cardiovascular imaging technology has been widely used for the diagnosis of CAD, the motion parameters of the heart and coronary arteries cannot be directly calculated from the images. In this paper, we propose a point set registration method with global and local topology constraints to quantify coronary artery movement. The global constraint is the motion coherence of the point set which enforces the smoothness of the displacement field. The local linear embedding based topological structure and the local feature descriptor i.e., the 3D shape context, are designed to retain the local structure of the point set. We incorporate these constraints into a maximum likelihood framework and derive an expectation-maximization algorithm to obtain the transformation function between the two point sets. The proposed method was compared with four existing algorithms using simulated data and applied to the real data obtained from 4D CT angiograms. For the simulation data, the proposed method achieves a lower registration error than the comparison algorithms. For the real data, the proposed method shows that, in most cases, the right coronary artery achieves a larger velocity than the left anterior descending and left circumflex branches, and there are three well-defined velocity peaks, during the cardiac cycle for these branches. The proposed approach is feasible and effective in quantifying coronary artery movement and thus adds to the diagnostic power of coronary imaging.


Characterization of the complete mitochondrial genome of Helice latimera and its phylogenetic implications in Brachyura.
Mitochondrial genomes (mitogenomes) help advance our learning of molecular evolution and phylogenetic relationships. The mitogenome of H. latimera is 16,246 bp in length, which typically contains 37 animal mitogenome genes consisting of 13 protein-coding genes (PCGs), two rRNA genes, and 22 tRNA genes, as well as a control region. The AT content of H. latimera is 69.1%. The A + T skew of the mitogenome of H. latimera was slightly negative (-0.017). The size of Thirteen PCGs is from 162 bp to 1731 bp. Twenty-two tRNA genes ranged from 62 to 73 bp and were highly A + T biased. All tRNA genes owed a typical cloverleaf structure, not including the trnS1 gene lacking a dihydroxyuridine arm. One PCG, two rRNAs, and 12 of the tRNAs were rearranged compared to the pancrustacean gene order. Phylogenetic analysis revealed the locationt of H. latimera among the Varunidae family.