Early to medium term outcomes of osteochondral lesions of the talus treated by autologous matrix induced chondrogenesis (AMIC).

BACKGROUND: The primary aim of the study is to evaluate the functional outcome following AMIC procedure in patients with osteochondral injury of the talus. The secondary aim is to evaluate if size of the lesion and patient's age influence outcome. MATERIALS AND METHODS: This is a retrospective study of 25 patients who underwent AMIC procedure of the talus treated by a single surgeon. Functional outcomes were evaluated using pre and post operative AOFAS and VAS scores. RESULTS: The mean lesion size was 1.74 cms with 88% of lesions in the study more than 1.4 cms. There was a significant improvement in AOFAS score with mean improvement of 49.40 (p < 0.05) and VAS score of 5.36 (p < 0.05). We could not find any correlation between either age or lesion size with functional outcome for AMIC procedure. CONCLUSION: AMIC procedure seems to be a reliable treatment method for larger diameter osteochondral lesions of the talus up to 2.5 cms in diameter.

Observation of preQ1-II riboswitch dynamics using single-molecule FRET.

PreQ1 riboswitches regulate the synthesis of the hypermodified tRNA base queuosine by sensing the pyrrolopyrimidine metabolite preQ1. Here, we use single-molecule FRET to interrogate the structural dynamics of apo and preQ1-bound states of the preQ1-II riboswitch from Lactobacillus rhamnosus. We find that the apo-form of the riboswitch spontaneously samples multiple conformations. Magnesium ions and preQ1 stabilize conformations that sequester the ribosome-binding site of the mRNA within the pseudoknotted structure, thus inhibiting translation initiation. Our results reveal that folding of the preQ1-II riboswitch is complex and provide evidence favoring a conformational selection model of effector binding by riboswitches of this class.

Structural analysis of a class III preQ1 riboswitch reveals an aptamer distant from a ribosome-binding site regulated by fast dynamics.

PreQ1-III riboswitches are newly identified RNA elements that control bacterial genes in response to preQ1 (7-aminomethyl-7-deazaguanine), a precursor to the essential hypermodified tRNA base queuosine. Although numerous riboswitches fold as H-type or HLout-type pseudoknots that integrate ligand-binding and regulatory sequences within a single folded domain, the preQ1-III riboswitch aptamer forms a HLout-type pseudoknot that does not appear to incorporate its ribosome-binding site (RBS). To understand how this unusual organization confers function, we determined the crystal structure of the class III preQ1 riboswitch from Faecalibacterium prausnitzii at 2.75 Å resolution. PreQ1 binds tightly (KD,app 6.5 ± 0.5 nM) between helices P1 and P2 of a three-way helical junction wherein the third helix, P4, projects orthogonally from the ligand-binding pocket, exposing its stem-loop to base pair with the 3' RBS. Biochemical analysis, computational modeling, and single-molecule FRET imaging demonstrated that preQ1 enhances P4 reorientation toward P1-P2, promoting a partially nested, H-type pseudoknot in which the RBS undergoes rapid docking (kdock ∼ 0.6 s(-1)) and undocking (kundock ∼ 1.1 s(-1)). Discovery of such dynamic conformational switching provides insight into how a riboswitch with bipartite architecture uses dynamics to modulate expression platform accessibility, thus expanding the known repertoire of gene control strategies used by regulatory RNAs.

Albendazole in the treatment of Hymenolepiasis in school children.

Hymenolepiasis is a helminthic and occasionally fatal disease of human imposing heavy economic losses to human society. Present study was aimed to diagnose the school children for the prevalence and control of Hymenolepiasis. A school based cross-sectional analysis of stool samples collected from 188 children aged 06-15 years was carried out (February to June 2016). Two stool samples were collected from each student before diagnosing and after treatment. The samples were fixed in 10% formalin and observed under the light microscope using the methods of direct smear in Lugol's solution, normal saline and flotation techniques. On the basis of drugs accessibility all the H. nana infected children were divided in to 2- groups. Children in group A were treated with albendazole (bendazol) 400mg once orally, group B was treated with albendazole (zentel) 200mg orally. Eggs per gram of faeces were counted in each group before and after treatment. Of the 188 children, current study reveals only 6.08% (n=18/296) infection with H.nana and 10.5% (n=16/151) were diagnosed with co infections. The % efficacy of albendazole (Zentel) and albendazole (bendazol) against Hymenolepis nana infection was reported as 83% and 75% respectively. Present study was concluded that albendazole (zentel) is the drug of choice for the treatment of hymenolepiasis in children.

Use of the ketogenic diet in the neonatal intensive care unit-Safety and tolerability.

Drug-resistant epilepsy poses a challenge in neonatal patients, especially those in the neonatal intensive care unit (NICU), who have various secondary comorbidities. We present results of four children with a history of drug-resistant epilepsy for whom a ketogenic diet was initiated and used in the NICU. A nonfasting induction into ketosis over 1-2 weeks was utilized, with gradual increases in the ketogenic ratio every 2-3 days. Data were collected retrospectively from a database, which included medical history, daily progress notes, relevant laboratory data, and imaging and diagnostic information. The ketogenic diet was well tolerated in all cases. The most common side effects observed were constipation, hypoglycemia, and weight loss. Serum ß-hydroxybutyrate levels demonstrated improved reliability as a marker of ketosis when compared to urine ketones in this population. Perceived benefits to the infants included improved seizure control, increased alertness, and decreased need for invasive respiratory support. These cases demonstrate that the use of the ketogenic diet for treatment of neonatal encephalopathy and refractory epilepsy can be undertaken safely in the NICU and is well tolerated by carefully screened neonates and infants.

Small scale production and characterization of xanthan gum synthesized by local isolates of Xanthomonas campestris.

Xanthan gum is a commercially important microbial exopolysaccharide (EPS) produced by Xanthomonas campestris. X. campestris is a plant pathogen causing various plant diseases such as black rot of crucifers, bacterial leaf blight and citrus canker disease resulting in crop damage. In this study, we isolated efficient local bacterial isolates which are capable to produce xanthan gum utilizing different sources of carbon (maltose, sucrose and glucose). Bacterial isolates from different plant leaves and fruits were identified as Xanthomonas campestris based on their morphological and biochemical characteristics. Among the 23 isolates, 70% were capable of producing gum. Taro plant, considered as new bacterial host, also have the capability to produce xanthan gum. Production conditions of xanthan gum and their relative viscosity by these bacterial isolates were optimized using basal medium containing commercial carbon and nitrogen sources and various temperature and rotation. Highest level of xanthan gum (18.286 g/l) with relative viscosity (7.2) was produced (Host, Citrus macroptera) at 28 degrees C, pH 7.0, 150 rpm using sucrose as a carbon source at orbital shaker. Whereas, in lab fermenter, same conditions gave best result (19.587 g/l gum) with 7.8 relative viscosity. Chilled alcohol (96%) was used to recover the xanthan gum. FTIR studies also carried out for further confirmation of compatibility by detecting the chemical groups.

Structure of a class II preQ1 riboswitch reveals ligand recognition by a new fold.

PreQ1 riboswitches regulate genes by binding the pyrrolopyrimidine intermediate preQ1 during the biosynthesis of the essential tRNA base queuosine. We report what is to our knowledge the first preQ1-II riboswitch structure at 2.3-Å resolution, which uses a previously uncharacterized fold to achieve effector recognition at the confluence of a three-way helical junction flanking a pseudoknotted ribosome-binding site. The results account for translational control mediated by the preQ1-II riboswitch class and expand the known repertoire of ligand-binding modes used by regulatory RNAs.

Ischemic stroke as an initial presentation of neurosyphilis in a newly diagnosed HIV patient: A case report and literature review.

With syphilis resurgence, physicians should be more vigilant to infection-induced cerebral vasculitis in high-risk patients presenting with neurological symptoms. In this case, neurosyphilis should not be missed. Thorough serologic screening and lumbar puncture are crucial for diagnosis, and further research is needed for safe and effective treatments in these populations.

Phosphorus Application Enhances Root Traits, Root Exudation, Phosphorus Use Efficiency, and Seed Yield of Soybean Genotypes.

Phosphorus (P) is a vital macronutrient required for soybean growth and development but is a finite resource in agriculture worldwide. Low inorganic P availability in soil is often a significant constraint for soybean production. However, little is known about the response of P supply on agronomic, root morphology, and physiological mechanisms of contrasting soybean genotypes at various growth stages and the possible effects of different P on soybean yield and yield components. Therefore, we conducted two concurrent experiments using the soil-filled pots with six genotypes (deep-root system: PI 647960, PI 398595, PI 561271, PI 654356; and shallow-root system: PI 595362, PI 597387) and two P levels [0 (P0) and 60 (P60) mg P kg-1 dry soil] and deep PVC columns with two genotypes (PI 561271 and PI 595362) and three P levels [0 (P0), 60 (P60), and 120 (P120) mg P kg-1 dry soil] in a temperature-controlled glasshouse. The genotype × P level interaction showed that increased higher P supply increased leaf area, shoot and root dry weights, total root length, shoot, root, and seed P concentrations and contents, P use efficiency (PUE), root exudation, and seed yield at different growth stages in both experiments. At the vegetative stage (Experiment 1), shallow-rooted genotypes with shorter life cycles had more root dry weight (39%) and total root length (38%) than deep-rooted genotypes with longer life cycles under different P levels. Genotype PI 654356 produced significantly higher (22% more) total carboxylates than PI 647960 and PI 597387 under P60 but not at P0. Total carboxylates positively correlated with root dry weight, total root length, shoot and root P contents, and physiological PUE. The deep-rooted genotypes (PI 398595, PI 647960, PI 654356, and PI 561271) had the highest PUE and root P contents. In Experiment 2, at the flowering stage, genotype PI 561271 had the greatest leaf area (202%), shoot dry weight (113%), root dry weight (143%), and root length (83%) relative to the short-duration, shallow-rooted genotype PI 595362 with external P applied (P60 and P120), with similar trends at maturity. PI 595362 had a greater proportion of carboxylates as malonate (248%), malate (58%), and total carboxylates (82%) than PI 561271 under P60 and P120 but no differences at P0. At maturity, the deep-rooted genotype PI 561271 had greater shoot, root, and seed P contents and PUE than the shallow-rooted genotype PI 595362 under increased P rates but no differences at P0. Further, the genotype PI 561271 had higher shoot (53%), root (165%), and seed yield (47%) than PI 595362 with P60 and P120 than P0. Therefore, inorganic P application enhances plant resistance to the soil P pool and maintains high soybean biomass production and seed yield.

Outbreak of dengue fever in Lahore: study of risk factors.

BACKGROUND: Dengue fever is a rapidly emerging arthropod born viral disease threatening to become an international public health problem. Approximately 500,000 people suffer from dengue haemorrhagic fever and dengue shock syndrome with 20,000 deaths annually. Objective of this study was to look into the risk factors associated with the development of dengue fever. METHODS: This cross-sectional descriptive study was conducted on patients admitted in various hospitals of Lahore with suspected Dengue fever. Data was collected on a questionnaire from 109 conveniently selected patients. RESULTS: Mean age of the patients was 34 +/- 16.5 years, and majority (80, 73.4%) were male. Seropositivity for dengue was found in 78 (71.5%). The study did not find significant statistical association of seropositivity with demographic variables. However, source of water supply was found associated with dengue seropositivity (p = 0.002). CONCLUSION: Source of water is a determinant of contracting dengue fever owing to it a breeding media for mosquitoes. All other phenomena associated with use of water and sanitation needs to be part of long term control of dengue that will also contribute to controlling other diseases with the same determinants.

Slowing deforestation in Indonesia follows declining oil palm expansion and lower oil prices.

Much concern about tropical deforestation focuses on oil palm plantations, but their impacts remain poorly quantified. Using nation-wide interpretation of satellite imagery, and sample-based error calibration, we estimated the impact of large-scale (industrial) and smallholder oil palm plantations on natural old-growth ("primary") forests from 2001 to 2019 in Indonesia, the world's largest palm oil producer. Over nineteen years, the area mapped under oil palm doubled, reaching 16.24 Mha in 2019 (64% industrial; 36% smallholder), more than the official estimates of 14.72 Mha. The forest area declined by 11% (9.79 Mha), including 32% (3.09 Mha) ultimately converted into oil palm, and 29% (2.85 Mha) cleared and converted in the same year. Industrial plantations replaced more forest than detected smallholder plantings (2.13 Mha vs 0.72 Mha). New plantations peaked in 2009 and 2012 and declined thereafter. Expansion of industrial plantations and forest loss were correlated with palm oil prices. A price decline of 1% was associated with a 1.08% decrease in new industrial plantations and with a 0.68% decrease of forest loss. Deforestation fell below pre-2004 levels in 2017-2019 providing an opportunity to focus on sustainable management. As the price of palm oil has doubled since the start of the COVID-19 pandemic, effective regulation is key to minimising future forest conversion.

Proof-of-Concept of Detection of Counterfeit Medicine through Polymeric Materials Analysis of Plastics Packaging.

The detection of counterfeit pharmaceuticals is always a major challenge, but the early detection of counterfeit medicine in a country will reduce the fatal risk among consumers. Technically, fast laboratory testing is vital to develop an effective surveillance and monitoring system of counterfeit medicines. This study proposed the combination of Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) and Differential Scanning Calorimetry (DSC) for the quick detection of counterfeit medicines, through the polymer analysis of blister packaging materials. A sample set containing three sets of original and counterfeit medicine was analyzed using ATR-FTIR and DSC, while the spectra from ATR-FTIR were employed as a fingerprint for the polymer characterization. Intending to analyze the polymeric material of each sample, DSC was set at a heating rate of 10 °C min-l and within a temperature range of 0- 400 °C, with nitrogen as a purge gas at a flow rate of 20 ml min-an. The ATR-FTIR spectra revealed the chemical characteristics of the plastic packaging of fake and original medicines. Further analysis of the counterfeit medicine's packaging with DSC exhibited a distinct difference from the original due to the composition of polymers in the packaging material used. Overall, this study confirmed that the rapid analysis of polymeric materials through ATR-FTIR and comparing DSC thermograms of the plastic in their packaging effectively distinguished counterfeit drug products.

Effects of Running Surface Stiffness on Three-Segment Foot Kinematics Responses with Different Shod Conditions.

OBJECTIVE: The aim of this study was to investigate the effects of surface stiffness on multisegment foot kinematics and temporal parameters during running. METHODS: Eighteen male subjects ran on three different surfaces (i.e., concrete, artificial grass, and rubber) in both heeled running shoes (HS) and minimal running shoes (MS). Both these shoes had dissimilar sole profiles. The heeled shoes had a higher sole at the heel, a thick base, and arch support, whereas the minimal shoes had a flat base sole. Indeed, the studied biomechanical parameters responded differently in the different footwear during running. Subjects ran in recreational mode speed while 3D foot kinematics (i.e., joint rotation and peak medial longitudinal arch (MLA) angle) were determined using a motion capture system (Qualysis, Gothenburg, Sweden). Information on stance time and plantar fascia strain (PFS) was also collected. RESULTS: Running on different surface stiffness was found to significantly affect the peak MLA angles and stance times for both HS and MS conditions. However, the results showed that the joint rotation angles were not sensitive to surface stiffness. Also, PFS showed no relationship with surface stiffness, as the results were varied as the surface stiffness was changed. CONCLUSION: The surface stiffness significantly contributed towards the effects of peak MLA angle and stance time. These findings may enhance the understanding of biomechanical responses on various running surfaces stiffness in different shoe conditions.

Transcriptomic in silico analysis of bovine Escherichia coli mastitis highlights its immune-related expressed genes as an effective biomarker.

BACKGROUND: Mastitis is one of the major diseases causing economic loss to the dairy industry by reducing the quantity and quality of milk. Thus, the objective of this scientific study was to find new biomarkers based on genes for the early prediction before its severity. METHODS: In the present study, advanced bioinformatics including hierarchical clustering, enrichment analysis, active site prediction, epigenetic analysis, functional domain identification, and protein docking were used to analyze the important genes that could be utilized as biomarkers and therapeutic targets for mastitis. RESULTS: Four differentially expressed genes (DEGs) were identified in different regions of the mammary gland (teat cistern, gland cistern, lobuloalveolar, and Furstenberg's rosette) that resulted in 453, 597, 577, and 636 DEG, respectively. Also, 101 overlapped genes were found by comparing 27 different expressed genes. These genes were associated with eight immune response pathways including NOD-like receptor signaling pathway (IL8, IL18, IL1B, PYDC1) and chemokine signaling pathway (PTK2, IL8, NCF1, CCR1, HCK). Meanwhile, 241 protein-protein interaction networks were developed among overlapped genes. Fifty-seven regulatory events were found between miRNAs, expressed genes, and the transcription factors (TFs) through micro-RNA and transcription factors (miRNA-DEG-TF) regulatory network. The 3D structure docking model of the expressed genes proteins identified their active sites and the binding ligands that could help in choosing the appropriate feed or treatment for affected animals. CONCLUSIONS: The novelty of the distinguished DEG and their pathways in this study is that they can precisely improve the detection biomarkers and treatments techniques of cows' Escherichia coli mastitis disease due to their high affinity with the target site of the mammary gland before appearing the symptoms.

Bis{4-[(2-hy-droxy-5-meth-oxy-3-nitro-benzyl-idene)amino]-phen-yl} ether.

The mol-ecule of the title compound, C28H22N4O9, exhibits crystallographically imposed twofold rotational symmetry, with a dihedral angle of 66.0 (2)° between the planes of the two central benzene rings bounded to the central oxygen atom. The dihedral angle between the planes of the central benzene ring and the terminal phenol ring is 4.9 (2)°. Each half of the mol-ecule exhibits an imine E configuration. An intra-molecular O-H⋯N hydrogen bond is present. In the crystal, the mol-ecules are linked into layers parallel to the ab plane via C-H⋯O hydrogen bonds. The crystal studied was refined as a two-component pseudomerohedral twin.

Adaptive Molecular Evolution of AKT3 Gene for Positive Diversifying Selection in Mammals.

The V-Akt Murine Thymoma Viral Oncogene Homolog 3 (AKT3) gene is of the serine/threonine-protein kinase family and influences the production of milk fats and cholesterol by acting on the sterol administrative area restricting protein (SREBP). The AKT3 gene is highly preserved in animals, and during lactation in cattle, its expression increases. The AKT3 gene is expressed in the digestive system, mammary gland, and immune cells. A phylogenetic investigation was performed to clarify the evolutionary role of AKT3, by maximum probability. The AKT3 gene sequence data of various mammalian species was evident even with animals undergoing breeding selection. From 39 mammalian species studied, there was a signal of positive diversifying selection with Hominidae at 13Q, 16G, 23R, 24P, 121P, 294K, 327V, 376L, 397K, 445T, and 471F among other codon sites of the AKT3 gene. These sites were codes for amino acids such as arginine, proline, lysine, and leucine indicating major roles for the function of immunological proteins, and in particular, the study highlighted the importance of changes in gene expression of AKT3 on immunity.

Independent Review Of Research Proposals From Ethical Point Of View In Pakistan.

BACKGROUND: Ethics is a part of subject philosophy and gained importance in research after the Nuremberg Code that led to Helsinki's Declaration on research ethics. In most developed countries stringent measures are taken to implement ethics in research. Awareness is on the rise in developing countries too. METHODS: This cross-sectional part of mixed methods design of study is part of a PhD thesis. Data was collected from medical institutions including medical colleges, medical universities, dental colleges, and teaching hospitals of Pakistan. Questionnaires were developed, and final version was adopted after pretesting. Questionnaires were sent via registered post. RESULTS: A total of 78 institutions responded. Out of 78, 48 (61.5%) were in public sector and 30(38.5%) in private sector. Seventy-four (94%) had institutional review boards. The numbers of members ranged from 1 to 15 with 40(54%) having number of members from 3 to 7. Out of 74 with IRBs, 17(23%) had members from community, 11(15%) had religious scholars and 8(11%) had members from legal background. Sixty-four (86.5%) responded that they had time frames for research proposal processing that ranged from one to 26 weeks (6.2±5.6). CONCLUSIONS: It is concluded that most of the medical institutions where research is conducted and approved through deficient research ethical boards in terms of their constitution. Research ethics is not a priority area for most of the institutions. Representation of society at large is missing. National action is required at government level.

Comparative Analysis of V-Akt Murine Thymoma Viral Oncogene Homolog 3 (AKT3) Gene between Cow and Buffalo Reveals Substantial Differences for Mastitis.

AKT3 gene is a constituent of the serine/threonine protein kinase family and plays a crucial role in synthesis of milk fats and cholesterol by regulating activity of the sterol regulatory element binding protein (SREBP). AKT3 is highly conserved in mammals and its expression levels during the lactation periods of cattle are markedly increased. AKT3 is highly expressed in the intestine followed by mammary gland and it is also expressed in immune cells. It is involved in the TLR pathways as effectively as proinflammatory cytokines. The aims of this study were to investigate the sequences differences between buffalo and cow. Our results showed that there were substantial differences between buffalo and cow in some exons and noteworthy differences of the gene size in different regions. We also identified the important consensus sequence motifs, variation in 2000 upstream of ATG, substantial difference in the "3'UTR" region, and miRNA association in the buffalo sequences compared with the cow. In addition, genetic analyses, such as gene structure, phylogenetic tree, position of different motifs, and functional domains, were performed to establish their correlation with other species. This may indicate that a buffalo breed has potential resistance to disease, environment changes, and airborne microorganisms and some good production and reproductive traits.

A randomized phase II study of pelareorep and docetaxel or docetaxel alone in men with metastatic castration resistant prostate cancer: CCTG study IND 209.

BACKGROUND: Pelareorep is an oncolytic virus with activity in many cancers including prostate. It has in vitro synergism with microtubule-targeted agents. We undertook a clinical trial evaluating pelareorep in mCRPC patients receiving docetaxel. PATIENTS AND METHODS: In this randomized, open-label phase II study, patients received docetaxel 75mg/m2 on day 1 of a 21-day cycle and prednisone 5mg twice daily, in combination with pelareorep (arm A) or alone (arm B). The primary endpoint was 12 weeks lack of disease progression rate (LPD). RESULTS: Eighty-five pts were randomized. Median age was 69, ECOG performance status was 0/1/2 in 31%/66%/3% of patients. Bone/regional lymph node/liver metastases were present in 98%/24%/6%. The median prognostic score was slightly higher in Arm A (144 vs. 129 p= 0.005). Adverse events were as expected but more prevalent in arm A. The 12-week LPD rate was 61% and 52.4% in arms A/B (p=0.51). Median survival was 19.1 on Arm A and 21.1 months on Arm B (HR 1.83; 95% CI 0.96 to 3.52; p=0.06). No survival benefit of pelareorep was found. CONCLUSION: Pelareorep with docetaxel was tolerable with comparable LPD in both arms but response and survival were inferior and so this combination does not merit further study.

Recent loss of closed forests is associated with Ebola virus disease outbreaks.

Ebola virus disease (EVD) is a contagious, severe and often lethal form of hemorrhagic fever in humans. The association of EVD outbreaks with forest clearance has been suggested previously but many aspects remained uncharacterized. We used remote sensing techniques to investigate the association between deforestation in time and space, with EVD outbreaks in Central and West Africa. Favorability modeling, centered on 27 EVD outbreak sites and 280 comparable control sites, revealed that outbreaks located along the limits of the rainforest biome were significantly associated with forest losses within the previous 2 years. This association was strongest for closed forests (>83%), both intact and disturbed, of a range of tree heights (5->19 m). Our results suggest that the increased probability of an EVD outbreak occurring in a site is linked to recent deforestation events, and that preventing the loss of forests could reduce the likelihood of future outbreaks.