Machine learning augmented near-infrared spectroscopy: In vivo follow-up of cartilage defects.

OBJECTIVE: To assess the potential of near-infrared spectroscopy (NIRS) for in vivo arthroscopic monitoring of cartilage defects. METHOD: Sharp and blunt cartilage grooves were induced in the radiocarpal and intercarpal joints of Shetland ponies and monitored at baseline (0 weeks) and at three follow-up timepoints (11, 23, and 39 weeks) by measuring near-infrared spectra in vivo at and around the grooves. The animals were sacrificed after 39 weeks and the joints were harvested. Spectra were reacquired ex vivo to ensure reliability of in vivo measurements and for reference analyses. Additionally, cartilage thickness and instantaneous modulus were determined via computed tomography and mechanical testing, respectively. The relationship between the ex vivo spectra and cartilage reference properties was determined using convolutional neural network. RESULTS: In an independent test set, the trained networks yielded significant correlations for cartilage thickness (ρ = 0.473) and instantaneous modulus (ρ = 0.498). These networks were used to predict the reference properties at baseline and at follow-up time points. In the radiocarpal joint, cartilage thickness increased significantly with both groove types after baseline and remained swollen. Additionally, at 39 weeks, a significant difference was observed in cartilage thickness between controls and sharp grooves. For the instantaneous modulus, a significant decrease was observed with both groove types in the radiocarpal joint from baseline to 23 and 39 weeks. CONCLUSION: NIRS combined with machine learning enabled determination of cartilage properties in vivo, thereby providing longitudinal evaluation of post-intervention injury development. Additionally, radiocarpal joints were found more vulnerable to cartilage degeneration after damage than intercarpal joints.

Implementation of nutrition risk screening using the Malnutrition Universal Screening Tool across a large metropolitan health service.

BACKGROUND: A standardised nutrition risk screening (NRS) programme with ongoing education is recommended for the successful implementation of NRS. This project aimed to develop and implement a standardised NRS and education process across the adult bed-based services of a large metropolitan health service and to achieve a 75% NRS compliance at 12 months post-implementation. METHODS: A working party of Monash Health (MH) dietitians and a nutrition technician revised an existing NRS medical record form consisting of the Malnutrition Universal Screening Tool and nutrition management guidelines. Nursing staff across six MH hospital sites were educated in the use of this revised form and there was a formalised implementation process. Support from Executive Management, nurse educators and the Nutrition Risk Committee ensured the incorporation of NRS into nursing practice. Compliance audits were conducted pre- and post-implementation. RESULTS: At 12 months post-implementation, organisation-wide NRS compliance reached 34.3%. For those wards that had pre-implementation NRS performed by nursing staff, compliance increased from 7.1% to 37.9% at 12 months (P < 0.001). The improved NRS form is now incorporated into standard nursing practice and NRS is embedded in the organisation's 'Point of Care Audit', which is reported 6-monthly to the Nutrition Risk Committee and site Quality and Safety Committees. CONCLUSIONS: NRS compliance improved at MH with strong governance support and formalised implementation; however, the overall compliance achieved appears to have been affected by the complexity and diversity of multiple healthcare sites. Ongoing education, regular auditing and establishment of NRS routines and ward practices is recommended to further improve compliance.

Laser-irradiating infrared attenuated total reflection spectroscopy of articular cartilage: Potential and challenges for diagnosing osteoarthritis.

Objective: A prototype infrared attenuated total reflection (IR-ATR) laser spectroscopic system designed for in vivo classification of human cartilage tissue according to its histological health status during arthroscopic surgery is presented. Prior to real-world in vivo applications, this so-called osteoarthritis (OA) scanner has been tested at in vitro conditions revealing the challenges associated with complex sample matrices and the accordingly obtained sparse spectral datasets. Methods: In vitro studies on human knee cartilage samples at different contact pressures (i.e., 0.2-0.5 â€‹MPa) allowed recording cartilage degeneration characteristic IR signatures comparable to in vivo conditions with high temporal resolution. Afterwards, the cartilage samples were assessed based on the clinically acknowledged osteoarthritis cartilage histopathology assessment (OARSI) system and correlated with the obtained sparse IR data. Results: Amide and carbohydrate signal behavior was observed to be almost identical between the obtained sparse IR data and previously measured FTIR data used for sparse partial least squares discriminant analysis (SPLSDA) to identify the spectral regions relevant to cartilage condition. Contact pressures between 0.3 and 0.4 â€‹MPa seem to provide the best sparse IR spectra for cylindrical (d â€‹= â€‹3 â€‹mm) probe tips. Conclusion: Laser-irradiating IR-ATR spectroscopy is a promising analytical technique for future arthroscopic applications to differentiate healthy and osteoarthritic cartilage tissue. However, this study also revealed that the flexible connection between the laser-based analyzer and the arthroscopic ATR-probe via IR-transparent fiberoptic cables may affect the robustness of the obtained IR data and requires further improvements.

A comparison of two different techniques for the detection of blood parasite, Theileria annulata, in cattle from two districts in Khyber Pukhtoon Khwa Province (Pakistan).

The present study was carried out to determine the prevalence of Theileria annulata in large ruminants from two districts, Peshawar and Kohat, in Khyber Pukhtoon Khwa (Pakistan). Blood samples were collected from 95 cattle. Data on the characteristics of animals and herds were collected through questionnaires. No significant risk factors were found associated with the spread of tropical theileriosis in the study area. Two different parasite detection techniques, PCR amplification and screening of Giemsa stained slides, were compared and it was found that PCR amplification is a more sensitive tool (33.7% parasite detection), as compared to smear scanning (5.2% parasite detection) for the detection of Theileria annulata. 32 out of 95 animals, from both districts, produced the 721-bp fragment specific for Theileria annulata.

Infrared spectroscopy is suitable for objective assessment of articular cartilage health.

Objective: To evaluate the feasibility of Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy to detect cartilage degradation due to osteoarthritis and to validate the methodology with osteochondral human cartilage samples for future development towards clinical use. Design: Cylindrical (d â€‹= â€‹4 â€‹mm) osteochondral samples (n â€‹= â€‹349) were prepared from nine human cadavers and measured with FTIR-ATR spectroscopy. Afterwards, the samples were assessed with Osteoarthritis Research Society International (OARSI) osteoarthritis cartilage histopathology assessment system and divided into two groups: 1) healthy (OARSI 0-2) and 2) osteoarthritic (OARSI 2.5-6). The classification was done with partial least squares discriminant analysis model utilizing cross-model validation. Receiver operating characteristics curve analysis was performed and the area under curve (AUC) was calculated. Results: For all samples combined, classification accuracy was 73% with AUC of 0.79. Femoral samples had accuracy of 74% and AUC of 0.77, while tibial samples had accuracy of 66%, and AUC of 0.74. Patellar samples had accuracy of 84% and AUC of 0.91. Conclusions: The results indicate that FTIR-ATR spectroscopy can differentiate between healthy and osteoarthritic femoral, tibial and patellar human tissue. If combined with a fiber optic probe, FTIR-ATR spectroscopy could provide additional objective intraoperative information during arthroscopic surgeries, which could improve clinical outcomes.

Long-term exposure to traffic-related air pollution and selected health outcomes: A systematic review and meta-analysis.

The health effects of traffic-related air pollution (TRAP) continue to be of important public health interest. Following its well-cited 2010 critical review, the Health Effects Institute (HEI) appointed a new expert Panel to systematically evaluate the epidemiological evidence regarding the associations between long-term exposure to TRAP and selected adverse health outcomes. Health outcomes were selected based on evidence of causality for general air pollution (broader than TRAP) cited in authoritative reviews, relevance for public health and policy, and resources available. The Panel used a systematic approach to search the literature, select studies for inclusion in the review, assess study quality, summarize results, and reach conclusions about the confidence in the evidence. An extensive search was conducted of literature published between January 1980 and July 2019 on selected health outcomes. A new exposure framework was developed to determine whether a study was sufficiently specific to TRAP. In total, 353 studies were included in the review. Respiratory effects in children (118 studies) and birth outcomes (86 studies) were the most commonly studied outcomes. Fewer studies investigated cardiometabolic effects (57 studies), respiratory effects in adults (50 studies), and mortality (48 studies). The findings from the systematic review, meta-analyses, and evaluation of the quality of the studies and potential biases provided an overall high or moderate-to-high level of confidence in an association between long-term exposure to TRAP and the adverse health outcomes all-cause, circulatory, ischemic heart disease and lung cancer mortality, asthma onsetin chilldren and adults, and acute lower respiratory infections in children. The evidence was considered moderate, low or very low for the other selected outcomes. In light of the large number of people exposed to TRAP - both in and beyond the near-road environment - the Panel concluded that the overall high or moderate-to-high confidence in the evidence for an association between long-term exposure to TRAP and several adverse health outcomes indicates that exposures to TRAP remain an important public health concern and deserve greater attention from the public and from policymakers.

The acute effects of Waterpipe smoking on the cardiovascular and respiratory systems.

OBJECTIVE: To assess the acute effects of smoking in Waterpipe (WP) smokers in Ajman, United Arab Emirates (UAE). CONTEXT: 202 male volunteers aged > 17 years were included. Blood pressure, heart rate and respiratory rate values of each participant, before and after a 30 minute smoking session, were measured and compared. Standardized questionnaires were also answered. RESULTS: Mean increases in systolic blood pressure (16 +/- 1 mmHg), diastolic blood pressure (2 +/- 0.7 mmHg), heart rate (6.30 +/- 0.60 bpm) and respiratory rate (2 +/- 2 breathes/min) were observed (p < 0.001). 92% of smokers believed Waterpipe smoking (WPS) to be harmful to health and 77% of smokers took up WPS for reasons of leisure. Results from the questionnaire revealed a significant relationship between smokers' beliefs of WPS and attempts to quit smoking ie. smokers who believed waterpipe to be harmful were more likely to try to quit. Education had influence on smokers ideas on WPS. 69% of smokers who claimed hookah is harmful had university qualification and further 23% has highschool qualification. CONCLUSIONS: Smoking Waterpipe has significant effects on both the cardiovascular and respiratory system. Waterpipe smokers despite sound knowledge, show little concern towards health. Education plays an important role and creates awareness about the hazards of smoking practices, including Waterpipe.

Circulating tumour DNA is a potential biomarker for disease progression and response to targeted therapy in advanced thyroid cancer.

BACKGROUND: Conventional biomarkers in thyroid cancer are not disease specific and fluctuate in advanced disease, making interpretation difficult. Circulating tumour DNA (ctDNA) has been shown to be a useful biomarker in other solid tumours. This is a multimutational study of ctDNA over multiple timepoints, designed to test the hypothesis that ctDNA is a potential biomarker in patients with advanced thyroid cancer. METHODS: Mutational analysis of archival tumour tissue was performed using NGS with a targeted gene panel. Custom TaqMan assays were designed for plasma ctDNA testing using digital droplet polymerase chain reaction. Concentrations of detected ctDNA were correlated with the conventional biomarker concentration and axial imaging status defined by the Response Evaluation Criteria in Solid Tumours criteria. RESULTS: Tumour tissue from 51 patients was obtained, with the following histologies: 32 differentiated (differentiated thyroid cancer [DTC]), 15 medullary (medullary thyroid cancer [MTC]), three poorly differentiated and one anaplastic. NGS analysis detected variants in 42 (82%) of cases. Plasma was assayed for these patients in 190 samples, and ctDNA was detected in 67% of patients. Earlier detection of disease progression was noted in three patients with MTC. In two cases (PTC and ATC), where conventional biomarkers were not detectable, ctDNA was detected before disease progression. Changes in ctDNA concentration occurred earlier than conventional markers in response to disease progression in multiple patients with DTC receiving targeted therapies. CONCLUSION: The majority of patients with advanced thyroid cancer had detectable ctDNA. ctDNA measurement may offer superiority over conventional markers in several scenarios: earlier detection of progression in MTC; as an alternative biomarker when conventional markers are not available; more rapid assessment of the disease status in response to targeted therapies, thereby potentially allowing prompter discontinuation of futile therapies. These early results support the hypothesis that ctDNA may be a clinically useful biomarker in thyroid cancer.

Molecular detection of Anaplasma in apparently healthy Cholistan breed of cattle from the Bahawalpur district, Pakistan.

The present study was designed to report the prevalence of Anaplasma sp. in blood samples of Cholistan breed of cattle from Bahawalpur District and to determine the risk factors associated with the prevalence of this parasite. A total of 148 blood samples were randomly collected from apparently healthy cattle. On the sampling sites, data on the characteristics of the animals (species, gender, age) were collected through questionnaires. 47 blood samples (31.8% of total) produced the 577 base pairs DNA fragment specific for 16S rRNA gene of Anaplasma sp. by PCR amplification. Out of 47 Anaplasma sp. positive PCR products, 9 were found to be Anaplasma marginale by restriction with BssNa1 and 9 were confirmed to be Anaplasma phagocytophilum (A. phagocytophilum) as they amplified 550 bp fragment from the amplified MSP 2 gene of this species. Risk factor analysis indicated that the presence of parasite was not limited to a particular sex or age group of the infected animals. Comparison of hematological profile revealed that Anaplasma sp. positive cattle had significantly reduced levels of mean corpuscular volume (P=0.02) and eosinophils (P=0.02) than in parasite negative animals. While studied serum biochemical profile remain unaffected when compared between the two groups.

A report on the molecular detection and seasonal prevalence of Trypanosoma brucei in Dromedary Camels from Dera Ghazi Khan District in Southern Punjab (Pakistan).

The present study was designed for molecular detection of Trypanosoma brucei through PCR, by using kinetoplast DNA (kDNA) maxicircle primers, on seasonal basis and to demonstrate the effect of this parasite on complete blood count and selected parameters of serum biochemistry in camels from Southern Punjab (Pakistan). A total of 291 camel blood samples (61 male, 230 females) were collected from Dera Ghazi Khan District in Pakistan during March 2012 till February 2013 for Trypanosoma brucei detection by blood smear screening, micro hemato centrifugation and Polymerase chain reaction techniques. Twenty eight out of 291 blood samples (9.62%) produced a 164 bp DNA fragment specific for T. brucei. Only 6 blood samples (2.06%) were found parasite positive by microscopic examination and 13 (4.46%) were positive for microhematocrit centrifugation technique. Seasonal PCR based prevalence of trypanosomiasis was 6.9%, 13.7%, 9.7% and 8.1% during spring, summer, autumn and winter seasons respectively. T. brucei prevalence was not restricted to a particular age group or and gender of the studied animals (P > 0.05). A significant increase in WBC (P = 0.001), neutrophils (P = 0.004), ALT (P = 0.028) and decreased RBC (P < 0.000), hemoglobin (P < 0.000) and packed cell volume (P < 0.000) were detected in parasite positive as compared to the parasite negative blood samples. In conclusion, PCR is a more reliable and sensitive technique than conventional microscopic blood screening and microhematocrit centrifugation for the detection of T. brucei in camel blood. We recommend the use of PCR for the effective prophylactic detection of T. brucei in livestock in order to reduce economic losses.

Study on optical properties of l-valine doped ADP crystal.

Single crystal of l-valine doped ammonium dihydrogen phosphate has been grown by slow evaporation method at room temperature. The crystalline nature of the grown crystal was confirmed using powder X-ray diffraction technique. The different functional groups of the grown crystal were identified using Fourier transform infrared analysis. The UV-visible studies were employed to examine the high optical transparency and influential optical constants for tailoring materials suitability for optoelectronics applications. The cutoff wavelength of the title crystal was found to be 280nm with wide optical band gap of 4.7eV. The dielectric measurements were carried to determine the dielectric constant and dielectric loss at room temperature. The grown crystal has been characterized by thermogravimetric analysis. The second harmonic generation efficiency of the grown crystal was determined by the classical Kurtz powder technique and it is found to be 1.92 times that of potassium dihydrogen phosphate. The grown crystal was identified as third order nonlinear optical material employing Z-scan technique using He-Ne laser operating at 632.8nm.

Microglia-derived IL-1ß triggers p53-mediated cell cycle arrest and apoptosis in neural precursor cells.

Neurogenesis persists in the adult brain and can contribute to learning and memory processes and potentially to regeneration and repair of the affected nervous system. Deregulated neurogenesis has been observed in neuropathological conditions including neurodegenerative diseases, trauma and stroke. However, the survival of neural precursor cells (NPCs) and newly born neurons is adversely affected by the inflammatory environment that arises as a result of microglial activation associated with injury or disease processes. In the present study, we have investigated the mechanisms by which microglia affect NPC proliferation and survival. Importantly, we demonstrate that interleukin-1ß (IL-1ß) produced by lipopolysaccharide/interferon-γ-activated microglia is necessary to induce cell cycle arrest and apoptosis in NPCs in vitro. Mechanistically, we show that IL-1ß activates the tumor suppressor p53 through an oxidative stress-dependent mechanism resulting in p53-mediated induction of the cyclin-dependent kinase inhibitor p21 and the proapoptotic Bcl-2 (B-cell lymphoma-2) family members Puma (p53-upregulated modulator of apoptosis) and Noxa. Furthermore, we demonstrate that cell cycle arrest and apoptosis induced by recombinant IL-1ß or activated microglia is attenuated in p53-deficient NPCs. Finally, we have determined that IL-1ß induces NPC death via the p53-dependent induction of Puma leading to the activation of a Bax (Bcl-2-associated X protein)-mediated mitochondrial apoptotic pathway. In summary, we have elucidated a novel role for p53 in the regulation of NPC proliferation and survival during neuroinflammatory conditions that could be targeted to promote neurogenesis and repair in a number of neurological conditions.

PCR based detection of Theileria lestoquardi in apparently healthy sheep and goats from two districts in Khyber Pukhtoon Khwa (Pakistan).

The present study was carried out to determine the prevalence of Theileria lestoquardi from two districts of Khyber Pukhtoon Khwa (Kohat and Peshawar) in Pakistan and also to report the risk factors associated with the spread of ovine theileriosis. A total of 165 blood samples were collected from sheep (N = 44) and goats (N = 121) from randomly selected herds. Data on the characteristics of animals and the herds were collected through questionnaires. Five (3%) out of total 165 samples produced 730 base pairs DNA fragment, through PCR amplification of 18S SSU rRNA gene, specific for T. lestoquardi. All positive samples were from district Kohat while samples from Peshawar were found negative for this parasite. Statistical analysis indicated a significant association (P = 0.005) between sampling site and prevalence of T. lestoquardi. It was observed that presence of tick on the ruminant (P = 0.0007) and the dogs associated with the herd (P = 0.001) were highly significant risk factor for the spread of ovine theileriosis. It was also observed that mixed herds (containing both sheep and goats) were more prone to the parasite. We have concluded that PCR is a sensitive and reliable diagnostic tool for detection of T. lestoquardi in blood samples of small ruminants and can be used for the prophylactic screening and treatment of this blood parasite in order to increase the live stock production in Pakistan.

Prevalence of Anaplasma phagocytophilum in horses from Southern Punjab (Pakistan).

The present study was designed to optimize a PCR-RFLP protocol for the molecular detection of Anaplasma sp. and to compare its prevalence in blood samples of equines from Southern Punjab (Pakistan) and to find out the risk factors involved in the spread of anaplasmosis. A total of 210 blood samples were collected from equines from 2 sampling sites (Dera Ghazi Khan and Khanewal districts). Data on the animals' characteristics (age, species and gender) were collected through survey. PCR amplified the 577bp product specific for 16S rRNA gene of Anaplasma spp. in 9 blood samples (4.3% of total), [Dera Ghazi Khan (N = 3) and Khanewal (N = 6)]. These Anaplasma spp. positive blood samples were used for PCR amplification using A. phagocytophilum specific primers and parasite was detected in all of them. Also it was revealed that the characteristics of the animals i.e. age, gender, species had no significant association with the presence of Anaplasma sp. Hematological parameters remained unaffected while lymphocyte count was significantly lowered in A. phagocytophilum positive samples.

Primary immunolocalization of estrogen and progesterone target cells in the human anterior cruciate ligament.

To identify estrogen and progesterone target cells in the human anterior cruciate ligament immunohistochemical localization of both estrogen and progesterone receptors was performed in 17 specimens of human anterior cruciate ligament. All ligament specimens were obtained at surgery. Thirteen specimens were from women, and four were from men: the average age was 57 years (range, 18-78 years). Eleven specimens (from nine women and two men) came from total knee replacements for osteoarthritis of the knee: three (from two women and one man), from reconstructions of the anterior cruciate ligament: two (both from women), from medial meniscectomies; and one (from a man), from an amputation secondary to chondrosarcoma of the pelvis. An immunoperoxidase method using monoclonal antibodies to the estrogen and progesterone receptors was employed to identify estrogen and progesterone target cells in the anterior cruciate ligament. Staining of both receptors was demonstrable in 14 specimens and in the remaining three specimens less than 15% of the cells were stained. Both estrogen and progesterone receptors were localized to synoviocytes in the synovial lining, fibroblasts in the anterior cruciate ligament stroma and cells in the blood vessel walls of the ligament. This demonstration of receptors for estrogen and progesterone in the cells of anterior cruciate ligament suggests that female sex hormones may have an effect on its structure and composition.

Estrogen affects the cellular metabolism of the anterior cruciate ligament. A potential explanation for female athletic injury.

Investigations from this laboratory have established the presence of estrogen receptors in the human anterior cruciate ligament. This study further investigates the effects of 17 beta-estradiol on the cellular proliferation and collagen synthesis of fibroblasts derived from the rabbit anterior cruciate ligament. Fibroblast proliferation and collagen synthesis in response to near log concentrations of 17 beta-estradiol (at 0.0029, 0.025, 0.25, 2.5, and 25 ng/ml) were assessed by measuring [3H]thymidine and [14C]hydroxyproline incorporation, respectively. Collagen synthesis was significantly reduced with increasing local estradiol concentration (P < 0.001). Declining collagen synthesis was first noted at a 17 beta-estradiol concentration of 0.025 ng/ml. Within normal physiologic levels of estrogen (0.025 to 0.25 ng/ml), collagen synthesis was reduced by more than 40% of control, and at pharmacologic levels of 2.5 and 25 ng/ml, by more than 50% of control. A significant reduction of fibroblast proliferation was also observed with increasing estradiol concentrations (P = 0.023). Clinically, alterations in anterior cruciate ligament cellular metabolism caused by estrogen fluctuations may change the composition of the ligament, rendering it more susceptible to injury.

HIV-1 associated neuropathies in males; impotence and penile electrodiagnosis.

Value of the bulbocavernosus reflex latency versus nerve conduction velocity of the dorsal nerve of penis and penile brachial index was evaluated in HIV-1 infected asymptomatic and symptomatic men with and without an objective evidence of neuropathy. These studies revealed striking results in neuropathic group. Both asymptomatic and symptomatic patients with neuropathy exhibited a significant decrease (P < 0.0005) in the values of the nerve conduction velocity of the dorsal nerve of penis as well as penile brachial index in comparison with the controls of the same age group. However both types of non neuropathic patients showed a non significant difference in the above mentioned parameters with their respective controls. The latency of bulbocavernosus reflex showed no significant difference between the groups and was within the normal limits. A non significant association in the values of the study parameters among asymptomatic and symptomatic patients with and without neuropathy was also observed. These findings suggest an exclusively apparent sexual pathway for the penile dorsal nerve conduction and penile brachial index in both HIV-1 infected asymptomatic and AIDS positive men affected by neuropathic conditions, irrespective of their disease state. We thus conclude that a primary defective neuropathic mechanism may play an etiological role in the pathogenesis of erectile impotence in these patients.

Beta-lactamase producing Neisseria gonorrhea strains in Karachi.

Urethral or cervical swab of 255 patients attending Skin and Social Hygiene Centre and found positive for gram negative intracellular diplococci on direct microscopy were inoculated on Modified New York City (MNYC) medium and chocolate (heated blood) agar for isolation of neisseria gonorrhea. Growth of N. gonorrhea was obtained in 134 (52.5%) cases. These strains were tested for penicillin susceptibility by disc diffusion method and for the production of beta-lactamase by rapid penicillinase paper strip test and rapid chromogenic cephalosporin method. Penicillin resistance was found in 31 (23%) strains, of which twelve (9%) were beta-lactamase producers (PPNG), the remaining 19 (14%) strains were penicillin resistant beta-lactamase negative (Pen RB Neg). We conclude that PPNG as well as other penicillin resistant strains (Pen RB Neg) of neisseria gonorrhea are prevalent in our country and appropriate changes in the conventional therapeutic regime are desirable.