Clinical case: Differential diagnosis of idiopathic pulmonary fibrosis

Background

The diagnosis of idiopathic pulmonary fibrosis can be quite challenging, even after careful clinical evaluation, imaging and pathological tests. This case report intends to demonstrate and discuss these difficulties, especially those concerning the differential diagnosis with chronic hypersensitivity pneumonitis.

Case presentation

A 58-year-old white male presented with shortness of breath, dry cough, fatigue and weight loss for two months. He was a former smoker and had regular exposure to a parakeet and poultry. Physical examination revealed bilateral basal crackles and chest imaging showed subpleural cystic lesions and traction bronchiectasis with a right side and upper level predominance. Auto-antibodies and IgG immunoglobulins to parakeet and fungal proteins were negative. Lung function tests displayed moderate restriction, low diffusion capacity and resting hypoxaemia. Bronchoalveolar lavage showed increased lymphocytes (28%) and neutrophils (12%) and surgical lung biopsy was compatible with a pattern of usual interstitial pneumonia. According to the possibility of either idiopathic pulmonary fibrosis or chronic hypersensitivity pneumonitis, treatment included prednisolone, azathioprine, acetylcysteine and avoidance of contact with the parakeet, but there was an unfavorable response and the patient was subsequently referred for lung transplant.

Conclusion

Chronic hypersensitivity pneumonitis and idiopathic pulmonary fibrosis can present with the same clinical and radiological manifestations In this case, despite careful evaluation, no definite diagnosis could be achieved.

     

PKCδ as a Regulator for TGFβ1-Induced α-SMA Production in a Murine Nonalcoholic Steatohepatitis Model

The precise mechanism of TGFβ1 signaling in the progression of non-alcoholic steatohepatitis (NASH) has remained unclear. In particular, a potential regulatory mechanism by which PKCδ affects profibrogenic gene expression had never been explored. In this study, therefore, the role of PKCδ in TGFβ1 mediated α-SMA expression was investigated using NASH model mice. In preparation of the NASH model, male C57BL6/J mice were fed a methionine-choline-deficient (MCD) diet for 3 weeks, after which time they were intraperitoneally injected with lipopolysaccharide (LPS). In addition, Tlr4^Lps-d (CH3/HeJ) mice were used to demonstrate the TGFβ1 signaling’s dependency on TLR4 induction. Liver histology and hepatic hepatitis markers were investigated, and hepatic gene expression levels were determined by real-time PCR. Acute liver injury by LPS injection specifically elevated not only α-SMA expression but also phospho-PKCδ in this model. In contrast, Tlr4^Lps-d (CH3/HeJ) and blockade of TGFβ1 receptor by SB431542 resulted in a significant reduction of PKCδ activation and α-SMA expression. Moreover, the TGFβ1-induced α-SMA production was significantly reduced by a specific PKCδ inhibitor. These findings suggested that PKCδ plays a critical role in TGFβ1-induced α-SMA production in a NASH model. Thus, this was the first demonstration of the involvement of PKCδ in the regulation of α-SMA expression in NASH liver tissues, and the impaired induction of PKCδ phosphorylation by LPS in a steatohepatitis condition. Interestingly, treatment by PKCδ inhibitor caused dramatic reduction of myofibroblast activation, indicating that PKCδ represents a promising target for treating NASH.     

Effect of Sodium Bicarbonate Administration on Mortality in Patients with Lactic Acidosis: A Retrospective Analysis

Background

Lactic acidosis is a common cause of high anion gap metabolic acidosis. Sodium bicarbonate may be considered for an arterial pH <7.15 but paradoxically depresses cardiac performance and exacerbates acidosis by enhancing lactate production. This study aimed to evaluate the cause and mortality rate of lactic acidosis and to investigate the effect of factors, including sodium bicarbonate use, on death.

Methods

We conducted a single center analysis from May 2011 through April 2012. We retrospectively analyzed 103 patients with lactic acidosis among 207 patients with metabolic acidosis. We used SOFA and APACHE II as severity scores to estimate illness severity. Multivariate logistic regression analysis and Cox regression analysis models were used to identify factors that affect mortality.

Results

Of the 103 patients with a mean age of 66.1±11.4 years, eighty-three patients (80.6%) died from sepsis (61.4%), hepatic failure, cardiogenic shock and other causes. The percentage of sodium bicarbonate administration (p = 0.006), catecholamine use, ventilator care and male gender were higher in the non-survival group than the survival group. The non-survival group had significantly higher initial and follow-up lactic acid levels, lower initial albumin, higher SOFA scores and APACHE II scores than the survival group. The mortality rate was significantly higher in patients who received sodium bicarbonate. Sodium bicarbonate administration (p = 0.016) was associated with higher mortality. Independent factors that affected mortality were SOFA score (Exp (B) = 1.72, 95% CI = 1.12–2.63, p = 0.013) and sodium bicarbonate administration (Exp (B) = 6.27, 95% CI = 1.10–35.78, p = 0.039).

Conclusions

Lactic acidosis, which has a high mortality rate, should be evaluated in patients with metabolic acidosis. In addition, sodium bicarbonate should be prescribed with caution in the case of lactic acidosis because sodium bicarbonate administration may affect mortality.     

Whole-brain Functional Networks in Cognitively Normal,Mild Cognitive Impairment,and Alzheimer’s Disease

The conceptual significance of understanding functional brain alterations and cognitive deficits associated with Alzheimer’s disease (AD) process has been widely established. However, the whole-brain functional networks of AD and its prodromal stage, mild cognitive impairment (MCI), are not well clarified yet. In this study, we compared the characteristics of the whole-brain functional networks among cognitively normal (CN), MCI, and AD individuals by applying graph theoretical analyses to [¹⁸F] fluorodeoxyglucose positron emission tomography (FDG-PET) data. Ninety-four CN elderly, 183 with MCI, and 216 with AD underwent clinical evaluation and FDG-PET scan. The overall small-world property as seen in the CN whole-brain network was preserved in MCI and AD. In contrast, individual parameters of the network were altered with the following patterns of changes: local clustering of networks was lower in both MCI and AD compared to CN, while path length was not different among the three groups. Then, MCI had a lower level of local clustering than AD. Subgroup analyses for AD also revealed that very mild AD had lower local clustering and shorter path length compared to mild AD. Regarding the local properties of the whole-brain networks, MCI and AD had significantly decreased normalized betweenness centrality in several hubs regionally associated with the default mode network compared to CN. Our results suggest that the functional integration in whole-brain network progressively declines due to the AD process. On the other hand, functional relatedness between neighboring brain regions may not gradually decrease, but be the most severely altered in MCI stage and gradually re-increase in clinical AD stages.     

Sarcopenia Is Independently Associated with Cardiovascular Disease in Older Korean Adults: The Korea National Health and Nutrition Examination Survey (KNHANES) from 2009

Background

The association between sarcopenia and cardiovascular disease (CVD) in elderly people has not been adequately assessed. The aim of this study was to investigate whether CVD is more prevalent in subjects with sarcopenia independent of other well-established cardiovascular risk factors in older Korean adults.

Method

This study utilized the representative Korean population data from the Korea National Health and Nutrition Examination Survey (KNHANES) which was conducted in 2009. Subjects older than 65 years of age with appendicular skeletal muscle mass (ASM) determined by dual energy X-ray absorptiometry were selected. The prevalence of sarcopenia in the older Korean adults was investigated, and it was determined whether sarcopenia is associated with CVD independent of other well-known risk factors.

Results

1,578 subjects aged 65 years and older with the data for ASM were selected, and the overall prevalence of sarcopenia was 30.3% in men and 29.3% in women. Most of the risk factors for CVD such as age, waist circumference, body mass index, fasting plasma glucose and total cholesterol showed significant negative correlations with the ratio between appendicular skeletal muscle mass and body weight. Multiple logistic regression analysis demonstrated that sarcopenia was associated with CVD independent of other well-documented risk factors, renal function and medications (OR, 1.768; 95% CI, 1.075–2.909, P = 0.025).

Conclusions

Sarcopenia was associated with the presence of CVD independent of other cardiovascular risk factors after adjusting renal function and medications.     

Light Transmission and Preference of Eye Patches for Occlusion Treatment

Purpose

To investigate light transmission and preference for six eye patches for occlusion therapy.

Methods

Six patches were examined, including; Ortopad Fun Pack, Ortopad Flesh, Kawamoto A-1, Kawamoto A-2, 3M Opticlude, and Everade Eye Guard. The size and the presence of a light blocking pad of patches were investigated. The amount of light transmitted through the patches was evaluated, using a digital light meter and a model eye, in three different environments; indoors with fluorescent light, outdoors on a sunny day, and strong light from illuminator. After patching the normal eye, the flash visual evoked potential (VEP) was measured. Thirty patients with amblyopia or horizontal strabismus, who received occlusion therapy as initial treatment, were included. After using all six patches, patients completed a 7-item questionnaire regarding the patch preference for size, color and shape, adhesive power, pain with removal, skin irritation after removing patch, parent’s preference and overall opinion.

Results

All patches had a light-blocking pad, except the 3M Nexcare. Ortopad had the strongest light blocking power in the three environments, and the 3M Nexcare had the weakest power. In flash VEP, Ortopad and Kawamoto patches showed flat, but 3M Nexcare and Everade Eye Guard showed normal response. There were significant preferential differences among the patches in all the items of the questionnaire (P<0.05). In comparison between the patches respectively, 3M Nexcare received the lowest satisfaction in pain when removing a patch and skin irritation after removing a patch. Kawamoto A-2 received the lowest score in the overall satisfaction.

Conclusions

We found differences in the light-blocking power and in the preference of the various patches for the occlusion treatment. This is a pilot study regarding only characteristics and preferences of patches. Further clinical studies regarding the relationship between characteristics or preferences of patches and outcomes of occlusion treatment are needed.     

Tailoring of Localized Surface Plasmon Resonances of Core-Shell Au@Ag Nanorods by Changing the Thickness of Ag Shell

We report the synthesis and the characterization of core-shell Au@Ag nanorods through reduction by the wet chemical method. UV-visible absorption spectra of core-shell Au@Ag nanorods demonstrate the longitudinal mode of localized surface plasmon resonances (LSPRs) can be tailored from 724 to 786 nm by controlling the thickness of the silver shell, as is assessed by transmission electron microscope (TEM). Furthermore, the tunable and well-controlled LSPRs of core-shell Au@Ag nanorods are also investigated by numerical simulation using the finite difference time domain (FDTD) method, which strongly supports the experimental observations. The growth mechanism for core-shell Au@Ag nanorods is proposed, according to experimental observations and numerical calculations.     

Analysis of Mid-Infrared Surface Plasmon Modes in a Graphene-Based Cylindrical Hybrid Waveguide

A graphene-based cylindrical hybrid surface plasmon polariton waveguide, composed of a silicon nanowire core surrounded by a silica layer and then a graphene layer, is investigated using the finite-difference time-domain method. The analytical solutions and the numerical simulation show that an ultra-small mode area and a large propagation length can be achieved with this waveguide. Utilizing the perturbation theory of coupled mode, we demonstrate that the six lowest-order coupling modes originate from the coupling of the three lowest-order single-waveguide modes, and the m?=?1 order yy-coupling mode possesses the maximum coupling length and the minimum crosstalk. This waveguide can be used for photonic integrated circuits in the mid-infrared range.