Miracle-dz/UniFAR-FTUs huggingface dataset:
Measures of Clinical Outcome Before, During, and After Implementation of a Comprehensive Geriatric Hip Fracture Program: Is There a Learning Curve?

Objectives: To evaluate the effects of implementing a multidisciplinary geriatric hip fracture program on clinical outcome measures at our institution. Design: Retrospective comparative cohort study of consecutive patients treated before, during, and after implementation of this program, including patient data from electronic medical records and state death records. Setting: Single metropolitan level 2 regional trauma center and community hospital. Patients/Participants: Patients aged 60 years and older with operatively treated low-energy hip fractures were included. Patients with active cancer or a high-energy mechanism (motor vehicle crash or fall >3 ft) were excluded. Intervention: Patients were divided into 1 of 3 groups: (1) those treated before our hip fracture program (July 2008–April 2009), (2) during implementation of the hip fracture program (May 2009–Feb 2010), and (3) after the hip fracture program was instituted and participation was well established (March 2010–Dec 2010). Main Outcome Measures: Patient demographics, injury factors, and clinical outcomes, including performance measures (eg, time to medical clearance and surgery and length of stay) and patient deaths (in-hospital, 30 days, and 1 year), were compared. Results: There was significant improvement in clinical performance measures, including time to surgery and length of stay during and after implementation of our geriatric hip fracture program. The in-hospital mortality rate increased during the implementation phase of this program (P = 0.04). Once established, however, the in-hospital mortality decreased to a more typical level. Thirty-day and 1-year mortality rates were not significantly different among the 3 groups. Conclusions: Most clinical outcome measures improved significantly with implementation of our geriatric hip fracture program. Increased in-hospital mortality, however, was an unintended consequence seen while establishing this program and may represent a learning curve by health care providers. Patient demise in the longer term seemed to be unaffected by implementation of the program. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
ADAMTS13‐von Willebrand factor axis is involved in the pathophysiology of kidney ischaemia‐reperfusion injury

The ADAMTS13‐von Willebrand factor (vWF) axis has been suggested to play a critical role in the pathophysiology of ischaemia‐reperfusion injury (IRI) in the heart or brain. Therefore, we aimed to investigate whether this axis was involved in the pathophysiology of IRI‐induced acute kidney injury.
Fetal Programming: Prenatal Androgen Disrupts Positive Feedback Actions of Estradiol but Does Not Affect Timing of Puberty in Female Sheep1

Abstract We studied the impact of prenatal androgen exposure on the timing of onset of puberty, maintenance of cyclicity in the first breeding season, and the LH surge mechanism in female sheep. Pregnant sheep were injected with testosterone propionate (100 mg i.m.) twice each week from Day 30 to Day 90 (D30–90) or from Day 60 to Day 90 (D60–90) of gestation (term = 147 days). Concentrations of plasma progesterone and gonadotropins were measured in blood samples collected twice each week from control (n = 10), D60–90 (n = 13), and D30–90 (n = 3) animals. Rate of weight gain and initiation of estrous behavior were also monitored. After the first breeding season, when the animals entered anestrus, competency of the gonadotropin surge system to respond to estradiol positive feedback was tested in the absence or presence of progesterone priming for 12 days. Prenatally androgenized females had similar body weight gain and achieved puberty (start of first progestogenic cycle) at the same time as controls. Duration of the breeding season and the number of cycles that occurred during the first breeding season were similar between control and prenatally androgenized sheep. In contrast, prenatal exposure to androgens compromised the positive feedback effects of estradiol. Onset of LH/FSH surges following the estradiol stimulus was delayed in both groups of androgenized ewes compared with the controls in both the absence and presence of progesterone priming. In addition, the magnitude of LH and FSH surges in the two animals that surged in the D30–90 group were only one third and one half, respectively, of the magnitudes observed in the control and D60–90 groups. The present findings indicate that disruption of the surge system can account for the fertility problems that occur during adulthood in prenatally androgenized sheep.
A fidelity mechanism in DNA polymerase lambda promotes error‐free bypass of 8‐oxo‐dG

8‐oxo‐7,8‐dihydroxy‐2′‐deoxyguanosine (8‐oxo‐dG) has high mutagenic potential as it is prone to mispair with deoxyadenine (dA). In order to maintain genomic integrity, post‐replicative 8‐oxo‐dG:dA mispairs are removed through DNA polymerase lambda (Pol λ)‐dependent MUTYH‐initiated base excision repair (BER). Here, we describe seven novel crystal structures and kinetic data that fully characterize 8‐oxo‐dG bypass by Pol λ. We demonstrate that Pol λ has a flexible active site that can tolerate 8‐oxo‐dG in either the anti‐ or syn‐conformation. Importantly, we show that discrimination against the pro‐mutagenic syn‐conformation occurs at the extension step and identify the residue responsible for this selectivity. This residue acts as a kinetic switch, shunting repair toward long‐patch BER upon correct dCMP incorporation, thus enhancing repair efficiency. Moreover, this switch also provides a potential mechanism to increase repair fidelity of MUTYH‐initiated BER.
Functional Analysis of the Noncoding Regions of the Uukuniemi Virus (Bunyaviridae) RNA Segments

ABSTRACT The role of the variable portion of the noncoding regions (NCRs) of the three Bunyaviridae RNA segments (L, M, S) in transcription, replication, and packaging was studied using the recently developed plasmid-driven RNA polymerase I minigenome system for Uukuniemi (UUK) virus, genus Phlebovirus (11), as a model. Comparison of the different segments showed that all NCRs were sufficient to mediate transcription/replication of a minigenome but demonstrated decreased promoter strength in the order M > L > S. Chimeric minigenomes with flanking NCRs from different genome segments revealed that the number of total base pairs within the inverted, partially complementary ends was important for transcription and replication. Point mutations increasing the base-pairing potential produced increased reporter expression, indicating that complementarity between the 5′ and 3′ ends is crucial for promoter activity. The role of the intergenic region (IGR) located between the two open reading frames of the ambisense UUK virus S segment was analyzed by inserting this sequence element downstream of the reporter genes. The presence of the IGR was found to enhance reporter expression, demonstrating that efficient transcription termination, regulated by the IGR, is important for optimal minigenome mRNA translation. Finally, genome packaging efficacy varied for different NCRs and was strongest for L followed by M and S. Strong reporter gene activity was still observed after seven consecutive cell culture passages, indicating a selective rather than random genome-packaging mechanism. In summary, our results demonstrate that the NCRs from all three segments contain the necessary signals to initiate transcription and replication as well as packaging. Based on promoter strength, M-segment NCRs may be the preferred choice for the development of reverse genetics and minigenome rescue systems for bunyaviruses.
Lysophosphatidic acid stimulates actomyosin contraction in astrocytes

Lysophosphatidic acid (LPA) is an extracellular signaling molecule that can enter the central nervous system following injury or diseases that disrupt the blood‐brain‐barrier. Using a combination of time‐lapse microscopy, immunocytochemistry, and biochemical techniques, we demonstrate that LPA stimulates profound changes in astrocyte morphology that are due to effects on the actomyosin cytoskeleton. Flat astrocytes in primary culture display prominent actin stress fibers. Treatment with the myosin light chain kinase inhibitor, ML‐9, causes stress fiber dissolution and dramatic morphology changes including rounding of the cell body and the formation of processes. LPA can stabilize actin stress fibers and inhibit the morphology changes in ML‐9‐treated cells. Furthermore, this activity is dependent upon activation of the GTP‐binding protein Rho as evidenced by the ability of C3 exoenzyme, a specific inhibitor of Rho, to block the effect. Phosphorylation of the regulatory light (RLC) chain initiates conformational changes in myosin II that result in the formation of myosin filaments and the recruitment of actin into contractile stress fibers. LPA‐induced stabilization of stress fibers is accompanied by increases in phosphorylation of the RLC of myosin. Furthermore, astrocytes grown on flexible silicone undergo rapid contraction in response to LPA treatment. The forces generated by these cells manifest themselves as increased wrinkling in the silicone. The observed contraction and accompanying increases in regulatory light chain phosphorylation suggest that LPA‐induced signaling cascades in astrocytes regulate actin/myosin interactions. J. Neurosci. Res. 53:343–352, 1998. © 1998 Wiley‐Liss, Inc.
Thyrotropin releasing hormone (TRH): a new player in human hair‐growth control

Thyrotropin‐releasing hormone (TRH) is the most proximal component of the hypothalamic‐pituitary‐thyroid axis that regulates thyroid hormone synthesis. Since transcripts for members of this axis were detected in cultured normal human skin cells and since human hair follicles (HFs) respond to stimulation with thyrotropin we now have studied whether human HF functions are also modulated by TRH. Here we report that the epithelium of normal human scalp HFs expresses not only TRH receptors (TRH‐R) but also TRH itself at the gene and protein level. Stimulation of microdissected organ‐cultured HFs with TRH promotes hair‐shaft elongation prolongs the hair cycle growth phase (anagen) and antagonizes its termination by TGF‐β2. It also increases proliferation and inhibits apoptosis of hair matrix keratinocytes. These TRH effects may be mediated in part by reducing the ATM/Atr‐dependent phosphorylation of p53. By microarray analysis several differentially up‐ or down‐regulated TRH‐target genes were detected (e.g., selected keratins). Thus human scalp HFs are both a source and a target of TRH which operates as a potent hair‐growth stimulator. Human HFs provide an excellent discovery tool for identifying and dissecting nonclassical functions of TRH and TRH‐mediated signaling in situ, which emerge as novel players in human epithelial biology. —Gáspár, E. , Hardenbicker, C. , Bodó, E. , Wenzel B. Ramot Y. Funk W. Kromminga A. Paus R. Thyrotropin releasing hormone (TRH): a new player in human hair‐growth control. FASEB J. 24, 393–403 (2010). www.fasebj. org
Prevalence of musculoskeletal symptoms and associated factors: A cross-sectional study of metal workers in Bangladesh.

BACKGROUND There is a scarcity of evidence regarding musculoskeletal symptoms prevalence among metal workers at different worksites in Bangladesh. OBJECTIVE To determine the prevalence of musculoskeletal symptoms and associated factors among metal workers in Dhaka, Bangladesh. METHOD This cross-sectional study was performed in 5 out of 12 randomly selected metal tools manufacturing factories in Dhaka, Bangladesh. A total of 60 eligible participants (45 male and 15 female) were asked to complete the short Bengali version of the Dutch Musculoskeletal Questionnaire. In addition, observations within the workplace were performed using a predesigned checklist for identifying ergonomic risk factors. RESULTS Prevalence of musculoskeletal symptoms during the last 12 months preceding data collection was reportedly 85%. Body regions reported to be most affected were upper back and lower back, then the wrist. Socio-demographic factors were not found to be significantly associated with musculoskeletal symptoms. In contrast, awkward posture and repetitive movement were significantly related to reports of musculoskeletal symptoms for the last 12 months preceding data collection. CONCLUSION Results conclude that there is a high reported prevalence of musculoskeletal symptoms among metal workers, calling for an action on prevention and promotion in the work environment.
Capitalism from Below

More than 630 million Chinese have escaped poverty since the 1980s, reducing the fraction remaining from 82 to 10 percent of the population. This astonishing decline in poverty, the largest in history, coincided with the rapid growth of a private enterprise economy. Yet private enterprise in China emerged in spite of impediments set up by the Chinese government. How did private enterprise overcome these initial obstacles to become the engine of China’s economic miracle? Where did capitalism come from? Studying over 700 manufacturing firms in the Yangzi region, Victor Nee and Sonja Opper argue that China’s private enterprise economy bubbled up from below. Through trial and error, entrepreneurs devised institutional innovations that enabled them to decouple from the established economic order to start up and grow small, private manufacturing firms. Barriers to entry motivated them to build their own networks of suppliers and distributors, and to develop competitive advantage in self-organized industrial clusters. Close-knit groups of like-minded people participated in the emergence of private enterprise by offering financing and establishing reliable business norms. This rapidly growing private enterprise economy diffused throughout the coastal regions of China and, passing through a series of tipping points, eroded the market share of state-owned firms. Only after this fledgling economy emerged as a dynamic engine of economic growth, wealth creation, and manufacturing jobs did the political elite legitimize it as a way to jump-start China’s market society. Today, this private enterprise economy is one of the greatest success stories in the history of capitalism.
Evaluation of Double- and Triple-Antibiotic Combinations for VIM- and NDM-Producing Klebsiella pneumoniae by In Vitro Time-Kill Experiments

ABSTRACT Combination therapy is recommended for infections with carbapenemase-producing Klebsiella pneumoniae. However, limited data exist on which antibiotic combinations are the most effective. The aim of this study was to find effective antibiotic combinations against metallo-beta-lactamase-producing K. pneumoniae (MBL-KP). Two VIM- and two NDM-producing K. pneumoniae strains, all susceptible to colistin, were exposed to antibiotics at clinically relevant static concentrations during 24-h time-kill experiments. Double- and triple-antibiotic combinations of aztreonam, ciprofloxacin, colistin, daptomycin, fosfomycin, meropenem, rifampin, telavancin, tigecycline, and vancomycin were used. Synergy was defined as a ≥2 log10 decrease in CFU/ml between the combination and its most active drug after 24 h, and bactericidal effect was defined as a ≥3 log10 decrease in CFU/ml after 24 h compared with the starting inoculum. Synergistic or bactericidal activity was demonstrated for aztreonam, fosfomycin, meropenem, and rifampin in double-antibiotic combinations with colistin and also for aztreonam, fosfomycin, and rifampin in triple-antibiotic combinations with meropenem and colistin. Overall, the combination of rifampin-meropenem-colistin was the most effective regimen, demonstrating synergistic and bactericidal effects against all four strains. Meropenem-colistin, meropenem-fosfomycin, and tigecycline-colistin combinations were not bactericidal against the strains used. The findings of this and other studies indicate that there is great potential of antibiotic combinations against carbapenemase-producing K. pneumoniae. However, our results deviate to some extent from those of previous studies, which might be because most studies to date have included KPC-producing rather than MBL-producing strains. More studies addressing MBL-KP are needed.
New and safe experimental model of radiation-induced neurovascular histological changes for microsurgical research

The aim is to create a new and safe experimental model of radiation-induced neurovascular histological changes with reduced morbidity and mortality for use with experimental microsurgical techniques. Seventy-two Sprague–Dawley rats (250–300 g) were divided as follows: Group I: control group, 24 rats clinically evaluated during six weeks; Group II: evaluation of acute side-effects (two-week follow-up period), 24 irradiated (20 Gy) rats; and Group III: evaluation of subacute side-effects (six-week follow-up period), 24 irradiated (20 Gy) rats. Variables included clinical assessments, weight, vascular permeability (arterial and venous), mortality and histological studies. No significant differences were observed between groups with respect to the variables studied. Significant differences were observed between groups I vs II–III regarding survival rates and histological changes to arteries, veins and nerves. Rat body weights showed progressive increases in all groups, and the mortality rate of the present model is 10.4% compared with 30–40% in the previous models. In conclusion, the designed model induces selective changes by radiotherapy in the neurovascular bundle without histological changes affecting the surrounding tissues. This model allows therapeutic experimental studies to be conducted, including the viability of microvascular and microneural sutures post radiotherapy in the cervical neurovascular bundle.
Measurement of S-methylcysteine and S-methyl-mercapturic acid in human urine by alkyl-chloroformate extractive derivatization and isotope-dilution gas chromatography-mass spectrometry.

S-methylcysteine (SMC) is a minor amino acid naturally excreted in human urine, a protective agent against oxidative stress and a biotransformation product of the fumigant biocide methyl bromide and of nicotine. A metabolic source of SMC is catabolism of the repair catalytic protein MGMT (EC 2.1.1.37), which specifically removes the methyl group from the modified DNA nucleotide O-6-methyl-guanine to revert the normal GC base pairing. To assess the value of SMC and of S-methylmercapturic acid (SMMA) as candidate biomarkers of proliferative phenomena, a sensitive analytical method by GC-MS was applied in a pilot study of healthy subjects to assess their urinary elimination and the intra- and inter-individual variability. Extractive alkylation with butylchloroformate-n-butanol-pyridine (Husek technique) was employed for sample derivatization and isotope dilution GC-MS with S-[CD(3) ]-SMC and -SMMA was applied for specific and sensitive detection. To resolve the target analytes from the main coeluting interferents in the derivatized urine extract a medium-polarity stationary phase was employed. SMMA was not detected in the morning urine of three healthy fertile-age women followed for one month above the minimum detectable level of approx. 500 µg/L while SMC concentrations were in the 0.02-0.7 µg/mL range (n = 61) with large inter-day and inter-individual variations. In a young healthy male urine samples taken throughout a few days yielded concentrations in the same 90-810 µg/L range (n = 11). These preliminary results points at SMC as a candidate biomarker for the study of methylation turnover in several biochemical processes.
Positional Identification of RT1-B (HLA-DQ) as Susceptibility Locus for Autoimmune Arthritis

Rheumatoid arthritis (RA) is associated with amino acid variants in multiple MHC molecules. The association to MHC class II (MHC-II) has been studied in several animal models of RA. In most cases these models depend on T cells restricted to a single immunodominant peptide of the immunizing Ag, which does not resemble the autoreactive T cells in RA. An exception is pristane-induced arthritis (PIA) in the rat where polyclonal T cells induce chronic arthritis after being primed against endogenous Ags. In this study, we used a mixed genetic and functional approach to show that RT1-Ba and RT1-Bb (RT1-B locus), the rat orthologs of HLA-DQA and HLA-DQB, determine the onset and severity of PIA. We isolated a 0.2-Mb interval within the MHC-II locus of three MHC-congenic strains, of which two were protected from severe PIA. Comparison of sequence and expression variation, as well as in vivo blocking of RT1-B and RT1-D (HLA-DR), showed that arthritis in these strains is regulated by coding polymorphisms in the RT1-B genes. Motif prediction based on MHC-II eluted peptides and structural homology modeling suggested that variants in the RT1-B P1 pocket, which likely affect the editing capacity by RT1-DM, are important for the development of PIA.
Hepatocyte growth factor receptor in human RPE cells: implications in proliferative vitreoretinopathy.

PURPOSE To determine whether hepatocyte growth factor (HGF) receptor (HGFR) is expressed in retinal pigment epithelial (RPE) cells and to test whether RPE cells are responsive to HGF. To evaluate expression of HGFR in human donor eyes and in several epiretinal membranes associated with proliferative vitreoretinopathy and idiopathic epiretinal membranes. METHODS HGF-dependent migration and proliferation in primary and simian virus (SV) 40-transformed human RPE cells was studied using a Boyden chamber and [3H]thymidine uptake, respectively. The expression and tyrosine phosphorylation of HGFR protein was evaluated in RPE cells by immunoprecipitation and western blot analysis. Expression of HGFR in human donor eyes and in several epiretinal membranes associated with proliferative vitreoretinopathy (PVR) and idiopathic epiretinal membranes was analyzed by immunohistochemistry. RESULTS HGFR was expressed in RPE cells and was tyrosine-phosphorylated in response to HGF. Whereas HGF was a potent motogen for RPE cells, it induced only a modest, dose-dependent uptake of [3H]thymidine. Evaluation of human donor eyes showed that the RPE monolayer was the major cell type that was strongly positive for HGFR. HGFR was uniformly and readily detected in the cellular component of epiretinal membranes associated with PVR, whereas little or no HGFR was found in idiopathic epiretinal membranes. CONCLUSIONS HGFR is expressed in cultured RPE cells, in the RPE monolayer in human donor eyes, and in epiretinal membranes obtained from patients with PVR. Furthermore, HGF is a potent chemoattractant for cultured human RPE cells. These observations suggest a role for HGF and HGFR in normal function of RPE cells and in RPE-related disease such as PVR.
Risk factors and independent predictors of survival in patients with pulmonary epithelioid haemangioendothelioma. Review of the literature and a case report

Abstract: Pulmonary epithelioid haemangioendothelioma (PEH) is a rare pulmonary neoplasm. A patient with PEH with lymph node and pleural metastases that were discovered incidentally is described. An abnormal left upper lobe shadow was noticed on CXR in a 70‐year‐old woman during an assessment for the sudden onset of nausea and vomiting. Transbronchial lung biopsy did not provide a diagnosis. Lobectomy and lymph node resection were performed. The histological diagnosis of PEH was confirmed immunohistochemically by positive reactions to factor VIII‐related antigen and CD34. Data on 93 patients with PEH including the present case report were analysed by Cox regression analysis using forward stepwise method to identify the risk factors, and the independent predictors of survival in patients with PEH. It revealed that male, symptomatic patients, presence of cough, haemoptysis, chest pain, multiple unilateral nodules, pleural effusion, metastases to more than one site and lymph node metastases were all significant risk factors for PEH (P < 0.05). Symptomatic patients and presence of pleural effusion were the independent predictors of survival in patients with PEH.