Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.     

Wide-band polarization-independent tensile-strained InGaAs MQW-SOAgate

A high-performance tensile-strained InGaAs multi-quantum-well semiconductor optical amplifier (MQW-SOA) gate developed for wavelength-division-multiplexing (WDM) applications is reported. The -0.47% InGaAs-strained SOA gate has a very low polarization dependence of 0.3 dB over a driving current between 30 and 60 mA and a wide-input signal wavelength range from 1530 to 1580 nm. The fabrication tolerance of the mesa stripe width is very large, ranging from 1.0 to 1.75 μm. The MQW-SOA gate has an extinction ratio of more than 40 dB. The fiber-to-fiber lossless operation current is less than 50 mA over the fiber-amplifier gain band. The gating speed is less than 1 ns     

Data fitting with a spline using a real-coded genetic algorithm

To obtain a good approximation for data fitting with a spline, frequently we have to deal with knots as variables. The problem to be solved then becomes a continuous nonlinear and multivariate optimization problem with many local optima. Therefore, it is difficult to obtain the global optimum. In this paper, we propose a method for solving this problem by using a real-coded genetic algorithm. Our method can treat not only data with a smooth underlying function, but also data with an underlying function having discontinuous points and/or cusps. We search for the best model among candidate models by using the Bayes Information Criterion (BIC). With this, we can appropriately determine the number and locations of knots automatically and simultaneously. Five examples of data fitting are given to show the performance of our method.     

Subarachnoid haemorrhage induced proliferation of leptomeningeal cells and deposition of extracellular matrices in the arachnoid granulations and subarachnoid space. Immunhistochemical study

Subarachnoid haemorrhage (SAH) often leads to subarachnoid fibrosis and resultant normal pressure hydrocephalus; however, how subarachnoid fibrosis occurs is unknown. We examined the changes within arachnoid granulations (AGs) and the subarachnoid space (SAS) chronologically at the parasagittal region obtained from patients with SAH at autopsy and made comparison with controls by immunostaining for cytokeratin, specific marker for leptomeningeal cells and by the elastica Masson-Goldner methods. Within a week some AGs were torn, and many inflammatory cells filled the AGs and SAS. Cytokeratin positive cells were scarce. During the next two weeks cytokeratin positive cells increased. After three weeks, AGs and SAS were filled by dense deposits of extracellular matrices surrounded by multiple layers of leptomeningeal cells.     

Distribution of total uptime during a given time interval

The distribution of total uptime during a given time interval for a repairable system is obtained. The total uptime is the total amount of time the system is up (in operation) during the interval. It is assumed that: (1) the system starts to operate at the beginning of the interval and alternately takes only the two states, up and down (under repair); (2) repair restores the system to “like-new”. A simple approximation to the distribution function of total uptime for a shorter interval is presented     

A clinical study of respiratory infection isolating non-pathogenic Neisseria by transtracheal aspiration]

Neisseria species other than N. meningitidis and N. gonorrhoeae are generally regarded as commensal bacterial flora of the oropharynx, and little is known regarding cases of these non-pathogenic Neisseria species in the lower respiratory tract. We clinically examined respiratory tract infections from which non-pathogenic Neisseria species were isolated by transtracheal aspiration (TTA). The incidence of non-pathogenic Neisseria isolated was 54 (15.7%) out of 344 episodes of respiratory tract infections with isolated microorganisms from TTA, and was 17.6%, 15.8%, 14.3% for pneumonia, acute bronchitis, and chronic lower respiratory tract infection, respectively. All 54 episodes were isolated with other microorganisms such as alpha-Streptococcus spp. (75.9%), Haemophilus influenzae (25.9%) and anaerobics (22.2%). The isolation ratio according to the age group increased at 45 years of age or more, but did not increase with the advance of age. Predisposing factors were identified such as overt aspiration, iatrogenic procedure and heavy smoking. Cases without overt aspiration that had fevers of 38 degrees C or more or hypoxemia of less than PaO2 70 torr when detecting non-pathogenic Neisseria were observed more frequently in the aged than the non-aged. The findings suggest the detection of non-pathogenic Neisseria by TTA is influenced by the host state that the fall of microorganisms from the upper to lower respiratory tract cannot be defended or excluded by mucociliary transportation disorder due to underlying disease and smoking, or deterioration of physical status other than overt or silent aspiration.     

Molecular analysis of p21 and p27 genes in human pituitary adenomas

OBJECTIVES: To determine the prevalence of thyroid dysfunction in institutionalised elderly people in Cape Town and to assess the usefulness of an abnormal thyroid-stimulating hormone (TSH) concentration as a screening test in this group. DESIGN: Cross-sectional survey. SETTING: Four old-age homes in Cape Town. SUBJECTS: Old-age home residents aged 60 years and over. OUTCOME MEASURES: Serum concentrations of TSH, free thyroxine and free tri-iodothyronine. RESULTS: Serum TSH estimations were performed on 658 participants, and were abnormal in 103 (15.6%)-41 (6.2%) being elevated (> 5.0 microU/ml) and 62 (9.4%) being low (> 0.4 microU/ml). There were 3 newly diagnosed cases of hyperthyroidism and 7 of hypothyroidism. Subclinical disease was diagnosed in 40 subjects. The overall prevalence of thyroid dysfunction in this population was 11.2%. In 22 (3.4%) this had previously been recognised, while in 50 (7.8%) the dysfunction was newly diagnosed by the current survey. The positive predictive value of a TSH concentration > 20 microU/ml in predicting hypothyroidism is 67%, while it will predict 100% of cases of subclinical hypothyroidism. A TSH concentration < 0.1 microU/ml will predict 23% of cases of hyperthyroidism, but 81% of cases of subclinical disease. CONCLUSIONS: The prevalence of thyroid dysfunction in institutionalised elderly people in Cape Town is similar to that reported for elderly people in other centres. Thyroid dysfunction had not previously been recognised in approximately two-thirds of the subjects in this study. The serum TSH concentration is a reliable screening test for thyroid dysfunction in the elderly, but is less useful if used to identify biochemical thyroid disease. An elevated TSH concentration is a better predictor of thyroid dysfunction in the elderly than a depressed TSH concentration.     

Premixed flame propagating into a narrow channel at a high speed, part 2: Transient behavior of the properties of the flowing gas inside the channel

The behavior of a premixed flame propagating from a chamber into a narrow channel at a high speed was examined using high speed and instantaneous schlieren photography, ion current measurement with electrostatic probes, and temperature measurement with an optical method. From detailed measurements of flames passing through the channel, flame extinguishment in the channel, no matter whether transient or not, was found to occur due to quenching of the reacting gas by rapid turbulent mixing with cold fresh mixture at the downstream of the contraction region and by heat transfer to the cold channel walls. Extinguishment must occur when these heat losses exceed the heat released by the chemical reaction of the flowing mixture.     

Fabrication of a new substrate for atomic force microscopic observation of DNA molecules from an ultrasmooth sapphire plate

A new stable substrate applicable to the observation of DNA molecules by atomic force microscopy (AFM) was fabricated from a ultrasmooth sapphire (alpha-Al2O3 single crystal) plate. The atomically ultrasmooth sapphire as obtained by high-temperature annealing has hydrophobic surfaces and could not be used for the AFM observation of DNA. However, sapphire treated with Na3PO4 aqueous solution exhibited a hydrophilic character while maintaining a smooth surface structure. The surface of the wet-treated sapphire was found by x-ray photoelectron spectroscopy and AFM to be approximately 0.3 nm. The hydrophilic surface character of the ultrasmooth sapphire plate made it easy for DNA molecules to adhere to the plate. Circular molecules of the plasmid DNA could be imaged by AFM on the hydrophilic ultrasmooth sapphire plate.