Diminished degradation of myelin basic protein by anti-sulfatide antibody and interferon-gamma in myelin from glia maturation factor-deficient mice

In this study we show the effect of anti-sulfatide (RmAb) antibodies and inflammatory cytokines, TNF-alpha and IFN-gamma in inducing myelin basic protein (MBP) degradation in myelin isolated from control wild type (WT) and glia maturation factor (GMF)-deficient (GMF-KO) mice. GMF was not detected in isolated myelin from WT and GMF-KO mice although it is present in brains of WT mice. Our results show that calcium-dependent neutral protease activity caused significantly elevated degradation of 18.5 and/or 17.5kDa isoforms of MBP in WT myelin treated with RmAb or IFN-gamma. In contrast, MBP degradation in isolated myelin from GMF-KO mice remained unaffected following treatment with RmAb, IFN-gamma, or GM-CSF. Neither the 14kDa isoform of MBP nor proteolipid protein (PLP) showed an elevated degradation compared to controls. A virtual absence of GM-CSF, TNF-alpha and IFN-gamma in GMF-KO brain compared to WT was also evident when the animals were challenged with MOG 35-55. Additionally, the myelin from GMF-KO mice showed difference in distribution of myelin oligodendrocyte glycoprotein (MOG) and beta-tubulin in a sucrose density gradient myelin-axolemmal fractions compared to WT. Taken together, our data suggests a role for GMF in the biochemical organization of myelin and thereby its effect on MBP degradation induced by RmAb and IFN-gamma.     

Finger pulp reconstruction with thenar flap: Aesthetic and functional outcome

Purpose: Fingertip injuries are common in industrial production activities as well as in domestic work. Loss of pulp hampers daily life activities. Functional and aesthetic aspects are important in fingertip reconstruction. The bone is usually exposed along with soft tissue loss. Therefore to reconstruct the pulp flap with adequate bulk is required. Methods: We reported a case series of 12 patients with the injury over the volar aspect of distal phalanx of the index or middle finger. In all cases, laterally based thenar flap was chosen. The flap donor site was closed primarily in most of cases, while 4 patients required skin graft. The flap was detached between 2-3 weeks. Functional assessment was done using static and dynamic 2-point discrimination and range of motion at each joint. The aesthetic outcome was assessed through questionnaire. The results were analyzed using the unpaired t-test (SPSS version 21). Results: Partial necrosis occurred in 2 cases while rest of flaps survived successfully. Static 2-point discrimination ranged from 6e10 mm, mean 8.6 mm; and dynamic 2-point discrimination ranged from 8-10 mm, mean 8.9 mm. The mean satisfaction score was (4.0 ± 0.55). Conclusion: Thenar flap is a good choice for reconstruction of the finger pulp as it provides the bulk with good functional and aesthetic outcome.     

Development and validation of a questionnaire to assess socio-behavioural impact of COVID-19 on the general population

Background and aimThe aim of the study is to develop a valid and reliable tool to assess sociobehavioural changes due to COVID among the general population.MethodsThis mixed method study has two phases. Phase I for questionnaire development (literature review, focus group discussion, expert evaluation and pilot testing). Phase II for establishing construct validity via factor analysis and internal consistency via Cronbach’s ɑ by administering the questionnaire on 179 participants.ResultsA questionnaire comprising 33 questions and five domains was developed having Cronbach’s α of 0·82.ConclusionThe developed questionnaire is a concise, easy to administer and valid tool to assess socio-behavioural changes.     

Detection of abnormal proliferation in histologically 'normal' colonic biopsies using FTIR-microspectroscopy

BACKGROUND: Abnormal crypt proliferation and development in the colon has been associated with premalignant stages of colon cancer. Conventionally, molecular markers are used to detect abnormal crypt proliferation. METHODS: In the present work, feasibility studies of FTIR-MSP to distinguish between normal and abnormal crypts from colon biopsies that show normal histopathological features have been undertaken. RESULTS: The results indicate that abnormal crypts show deviations in the pattern of absorbance in the Mid IR region along the crypt height when compared with the normal crypts. The crypts could be empirically classified into three groups such as crypts having a normal absorbance pattern for all biochemical components, crypts with abnormal absorbance pattern for some biochemical components and crypts with completely abnormal absorbance pattern along the height for all or most biochemical components studied by FTIR. The utilization of FTIR-MSP is proposed for diagnosis of abnormal metabolism at the molecular level of histologically completely normal-looking crypts, especially from those biopsies that are taken from sites far away from cancer. CONCLUSIONS: This method could give rise to a reduction in false-negative results during examination of biopsies using the conventional histopathological methods. The present method may be complementary to existing methods for precise demarcation of the zone of colostomy prior to colon cancer surgery.     

An exercise-based cardiac rehabilitation programme for AF patients in the NHS: a feasibility study

There is increasing evidence for the role of exercise-based cardiac rehabilitation in the management of patients with atrial fibrillation (AF). However, this intervention has not yet been widely adopted within the National Health Service (NHS).We performed a feasibility study on the utilisation of an established NHS cardiac rehabilitation programme in the management of AF, and examined the effects of this intervention on exercise capacity, weight, and psychological health. We then identified factors that might prevent patients from enrolling on our programme.Patients with symptomatic AF were invited to participate in an established six-week exercise-based cardiac rehabilitation programme, composed of physical activity and education sessions. At the start of the programme, patients were weighed and measured, performed the six-minute walk test (6MWT), completed the Generalised Anxiety Disorder Questionnaire (GAD-7), and the Patient Health Questionnaire (PHQ-9). Measurements were repeated on completion of the programme.Over two years, 77 patients were invited to join the programme. Twenty-two patients (28.5%) declined participation prior to initial assessment and 22 (28.5%) accepted and attended the initial assessment, but subsequently withdrew from the programme. In total, 33 patients completed the entire programme (63.9 ± 1.7 years, 58% female). On completion, patients covered longer distances during the 6MWT, had lower GAD-7 scores, and lower PHQ-9 scores, compared with their baseline results. Compared with patients that completed the entire programme, those who withdrew from the study had, at baseline, a significantly higher body mass index (BMI), covered a shorter distance during the 6MWT, and had higher PHQ-9 and GAD-7 scores.In conclusion, enrolling patients with AF into an NHS cardiac rehabilitation programme is feasible, with nearly half of those invited completing the programme. In this feasibility study, cardiac rehabilitation resulted in an improved 6MWT, and reduced anxiety and depression levels, in the short term. Severe obesity, higher anxiety and depression levels, and lower initial exercise capacity appear to be barriers to completing exercise-based cardiac rehabilitation. These results warrant further investigation in larger cohorts.Key words: atrial fibrillation, cardiac rehabilitation, National Health Service     

Medullary carcinoma of thyroid metastasis to breast: A cytological experience

Medullary carcinoma of thyroid is a relatively uncommon malignancy, which can be sporadic and syndromic in nature. It commonly spreads to regional lymph nodes followed by spreading to distant sites. Breast is an uncommon site of metastasis of this malignancy. Our case is a 38‐year‐old woman married parous woman presenting to the outpatient department with complaints of lump in both the breasts. Fine‐needle aspiration (FNA) was attempted, which revealed a malignancy more suggestive of a metastasis, which was confirmed on CT scan. A detailed history revealed that the patient is a known case of medullary carcinoma of thyroid. The report was given as metastatic medullary carcinoma to the breast after confirming with a calcitonin immunostain. Given the versatility of primary lesions in the breast, minimally invasive FNA cytology (FNAC) technique with adequate sampling helps in identifying metastatic lesions. Differentiating primary from metastatic lesions changes the course of management to the patient. Metastatic lesions should always be kept in mind in the occurrence of known malignancies, however rare the site of occurrence may be. Morphological clues and immunohistochemical work up aid in arriving at correct diagnosis.     

Protein-activated transformation of silver nanoparticles into blue and red-emitting nanoclusters

Proteins are very effective capping agents to synthesize biocompatible metal nanomaterials in situ. Reduction of metal salts in the presence of a protein generates very different types of nanomaterials (nanoparticles or nanoclusters) at different pH. Can a simple pH jump trigger a transformation between the nanomaterials? This has been realized through the conversion of silver nanoparticles (AgNPs) into highly fluorescent silver nanoclusters (AgNCs) via a pH-induced activation with bovine serum albumin (BSA) capping. The BSA-capped AgNPs, stable at neutral pH, undergo rapid dissolution upon a pH jump to 11.5, followed by the generation of blue-emitting Ag₈NCs under prolonged incubation (∼9 days). The AgNPs can be transformed quickly (within 1 hour) into red-emitting Ag₁₃NCs by adding sodium borohydride during the dissolution period. The BSA-capping exerts both oxidizing and reducing properties in the basic solution; it first oxidizes AgNPs into Ag⁺ and then reduces the Ag⁺ ions into AgNCs.

Protein capping can trigger nanoparticle to nanocluster transformation at elevated pH.

Noble metal nanomaterials, especially silver (Ag) and gold (Au), have witnessed exceptional research exploration in the last couple of decades from both fundamental and application perspectives.¹ These nanomaterials mainly exist in two distinct size regimes with unique optical characteristics. Ultra-small nanoclusters (NCs) (size typically <3 nm) contain only a handful of atoms (few to hundred), while relatively large nanoparticles (NPs) may comprise thousands of atoms. NPs may display strong extinction (absorption or scattering) spectra in the UV-vis region but are generally non-fluorescent.² In contrast, metal nanoclusters (MNCs) exhibit bright emission but not so noteworthy absorption spectra.^3,4 The distinct optical characteristics of the two nanomaterials have been exploited in various applications. For example, metal nanoparticles (MNPs) are extensively used in photothermal therapy⁵ and imaging,⁶ while NCs are more suited in fluorescence imagining⁷ and sensing⁸ applications. A facile transformation between the two nanomaterials could enable us to combine the complementary optical properties in a single system. Moreover, the kinetics of transformation can provide insights on various intermediate processes like dissolution, etching and digestive ripening etc.^9–11Silver nanoparticles (AgNPs) and nanoclusters (AgNCs) are of particular interest, as it not only possess the intriguing physicochemical properties of MNPs and MNCs, but also feature unique properties pertaining to silver.^3,12,13 For example, metallic silver has been well known for its capability to prevent infection since the ancient times, while recent studies revealed that ultrasmall AgNCs exhibit even superior antibacterial properties towards a broad spectrum of bacteria.^13,14 Moreover, due to superior plasmonic properties and bright fluorescence, AgNPs and AgNCs are preferred over other metal nanomaterials.^15,16The fluorescence properties of AgNCs mainly be attributed to the quantum confinement effect or surface ligand effect.¹⁷ The strong fluorescence generally arises from the electronic transition between occupied d band and states above the Fermi level (sp bands) or the electronic transition between highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO).¹⁸ Several reviews have been devoted for the fundamental understanding of the fluorescence origin of AgNCs.^17,19 Recently, it was demonstrated that aggregation-induced emission (AIE) may also contribute to the luminescence pathway of MNCs.^19,20 The origin of AIE from MNCs could be attributed to the restriction of intramolecular vibration and rotation of ligand on the surface of MNCs after aggregation, which facilitates the radiative energy relaxation via inhibiting of non-radiative relaxations.^21,22Protein capping is quite common for obtaining both NPs^23,24 and NCs.^25–29 Serum proteins, bovine serum albumin (BSA) and human serum albumin (HSA) are the most popular among trials with different proteins.^26–29 BSA is a large protein which provides steric stabilization to the MNCs with its various functional group like –OH, –NH₂, –COOH, –SH.^25,30 The disulfide bond of BSA may have strong interaction with the MNCs where sulfur may be covalently bonded to the MNCs core.^24,31 The nanomaterials are synthesized within the protein template at very different pHs. AgNPs are obtained from the reduction of silver salts at neutral pH (6–8),²⁴ whereas the same process at a higher pH (>11) leads to AgNCs.^30,32 The protein capping itself may reduce Ag⁺; AgNCs are formed without any external reducing agent.^25,33 However, an external reducing agent may change the nature and kinetics of the NCs significantly.³⁰Thus, the influence of pH on the protein structure may govern the selective synthesis of AgNPs or AgNCs. BSA can achieve several conformations – N (native), B (basic), A (aged) and U (unfolded) as the pH of the medium gradually changes from neutral to highly alkaline.^34,35 It may be possible that a specific type of nanomaterial is stable within a particular conformation dictated by the pH of the medium. Hence, by simply changing the pH, we may expect a significant modulation of the morphology of the nanomaterial. Herein, we applied this concept to show an effortless transformation from AgNP to AgNC. Although BSA template is exceptionally popular in the preparation of both AgNPs and AgNCs, however, to the best of our knowledge, no report is available on the conversion from AgNP to AgNC within the protein capping.The BSA-capped AgNPs (BSA-AgNPs) were first synthesized at a neutral pH (pH = 6) using sodium borohydride reduction (see ESI^†). The AgNPs show a sharp surface plasmon resonance (SPR) band at 415 nm (Fig. 1a) and have uniform diameters of 12.5 ± 1.5 nm (Fig. 1b). The AgNPs are quite stable at this pH with no apparent change in the SPR band even after 15 days (Fig. S1^†).Open in a separate windowFig. 1(a) UV-vis spectrum and (b) TEM image of BSA-protected AgNPs synthesized at pH 6. The insets show the appearance of the AgNP solution under regular and UV light (left panel), and size distribution histogram (right panel).However, when the BSA-AgNPs were treated with NaOH to elevate the pH to 11.5, we observed a remarkable decrease in the SPR band at 415 nm and a color change from dark to light brown within 2 h of the pH jump (Fig. 2a). The observations indicate the dissolution of AgNPs, which was further confirmed from the TEM images taken quickly (∼10 min) after the NaOH treatment (Fig. S2^†). Heterogeneous distribution of AgNPs was obtained with sizes varying from 2.6 nm to 17 nm, which is in sharp contrast to the uniform AgNPs before the addition NaOH (cf.Fig. 1b). Upon further incubation (6 h), the light brown color gradually faded to light yellow with a further decrease in the SPR band absorbance (Fig. S3^†).Open in a separate windowFig. 2Time evaluation of the (a) UV-visible and (b) emission spectra (λ_ex = 370 nm) of BSA-capped AgNPs after enhancement of the pH from 6 to 11.5 (by addition of NaOH at t = 0). The inset shows the snapshot of the final blue-emitting AgNC solution under normal and UV lights. (c) TEM of the blue-emitting AgNCs along with the HRTEM image and the analyzed size distribution in the inset. (d) MALDI-mass spectra of the BSA protein and BSA-capped blue-emitting AgNCs.Interestingly, the solution also develops distinct fluorescence with a maximum at ∼460 nm after the addition of NaOH (Fig. 2b). The fluorescence intensity gradually grows up upon incubation, and finally, an intense blue fluorescence was developed within ∼9 days. The final NaOH-treated AgNP solution appears to be light yellow under normal light and blue-fluorescent when viewed under a hand-held UV lamp (Fig. 2b, inset). The blue-emitting AgNCs exhibit a single band excitation spectrum with a maximum at 372 nm (Fig. S4^†).TEM image of the optimized NCs (after 9 days incubation at 37 °C) exclusively reveals uniform AgNCs of ∼2.10 ± 0.28 nm diameter without any trace of large NPs (Fig. 2c). The mass of the BSA-capped AgNCs (67 375 Da) was shifted by 845 Da from that of native BSA (66 530 Da) (Fig. 2d). Thus, the new species should correspond to Ag₈ cluster. The characteristics of the blue-AgNCs were quite similar to the human serum albumin (HSA)-protected blue-AgNCs, directly prepared from silver salt.³³ However, the formation time of those AgNCs was significantly less (∼10 h) than the present method (∼9 days).³³ Thus, the initial dissolution process, although quite fast, may have a crucial role in the kinetics of the protein-protected NCs. When we performed a similar pH jump experiment on a citrate-stabilized AgNP,³⁶ the extinction spectrum of the AgNPs showed much less variation compared to the BSA-AgNPs. Instead of a strong decrease, the SRP band showed a red-shift with an extended tail indicating aggregation rather than dissolution of NPs (Fig. S5^†).Furthermore, a red-emitting cluster was generated when an external reducing agent, sodium borohydride (NaBH₄), was added during the dissolution process. NaBH₄ was added after ∼11 min of the NaOH addition when the SPR band of BSA-AgNP was already decreased by half (Fig. 3a). The SPR band (λ_max = 415 nm) of AgNP continues to diminish similarly before and after the addition of NaBH₄ (Fig. S3^†). Thus, NaBH₄ may not have any significant effect on the dissolution process of AgNP. However, it has a strong impact on the modulation of the fluorescence; a new fluorescence band was developed at ∼650 nm within a much shorter duration (1 h) (Fig. 3b). The solution exhibits a bright-red fluorescence under a UV lamp (Fig. 3b, inset) with a quantum yield of 3.5%.Open in a separate windowFig. 3Early time evolution of (a) UV-visible and (b) emission spectra (λ_ex = 370 nm) of the BSA-protected AgNPs upon subsequent treatments with NaOH (pH 11.5) and NaBH₄ at t = 0 and 11 min, respectively. The decrease of the SPR band at 415 nm and a concomitant increase of the fluorescence band at ∼650 nm indicates dissolution of the AgNPs and formation of the red-emitting cluster. The inset shows the visuals of the AgNCs formed after 1 h under normal light and UV light. (c) TEM of the red-emitting AgNCs along with the HRTEM image and the analyzed size distribution in the inset. (d) MALDI-mass spectra of the BSA protein and BSA-capped red-emitting AgNCs.TEM measurements of the red-emitting species show homogeneous distribution of AgNCs with ∼2.25 ± 0.25 nm diameter (Fig. 3c). MALDI-mass experiment further assigned the red-emitting species as Ag₁₃ cluster (Fig. 3d). The excitation spectrum (λ_em = 650 nm) displays two distinct peaks at 370 nm and 470 nm, which match closely to the reported excitation peaks of the Ag_13–15 clusters within BSA/HSA capping (Fig. S4^†).^30,32,33 Moreover, the fluorescence decay of the red-emitting-AgNCs converted from AgNP almost matches with those prepared directly from AgNO₃; both display very similar average lifetimes (0.95 ns vs. 0.89 ns) (Fig. S6 and Table S1^†).³⁷Another important observation is that the red-emitting AgNCs have only transient stability at 37 °C. With further incubation, the absorbance at ∼470 nm (characteristic excitation peak of the red-emitting cluster) reduces and the absorbance at 370 nm (excitation peak of the blue-emitting cluster) increases simultaneously (Fig. 4a). The red-emission at 650 nm also decreases gradually with a concomitant increase of a blue emission band at 465 nm (Fig. 4b). Thus, both absorption and emission measurements clearly indicate transformation of red- to blue-emitting clusters which takes up to ∼15 days for completion. The solution finally becomes light yellow and exhibits a bright blue fluorescence under UV light similar to the blue-emitting cluster obtained earlier from the AgNP in the absence of NaBH₄. Interestingly, other characteristics of the regenerated blue-emitting AgNCs (converted from Ag₁₃NCs) also match quite nicely with the directly prepared blue-AgNCs (converted from AgNPs in the absence of NaBH₄). The size of this blue cluster was 2.04 ± 0.12 nm, which is similar to the previously obtained direct blue-emitting cluster (2.10 ± 0.28) (Fig. 4c). Furthermore, MALDI-mass measurement reveals that both the blue-emitting clusters may have the same composition, Ag₈ (Fig. 4d). In addition to this, the average lifetime (0.53 ns) of the blue-emitting AgNCs synthesized from AgNP agrees well to the average lifetime (0.40 ns) of the blue-emitting AgNCs converted from the red-emitting AgNCs (Fig. S7 and Table S2^†). However, the quantum yield (23%) of blue-emitting AgNCs, converted from red-emitting AgNCs, was higher than the quantum yield (18%) of the blue-emitting AgNCs, converted from AgNPs. Since, the emission characteristics of the blue and the red-emitting clusters nearly matches with earlier report, we expect that silver may be present in the zero oxidation state as determined in those studies.^30,31Open in a separate windowFig. 4Transformation of red-emitting to blue-emitting cluster: (a) UV-visible and (b) emission spectra (λ_ex = 370 nm) showing transformation of the BSA-protected red-emitting Ag₁₃NCs (obtained at 1 h) to blue-emitting AgNC upon prolonged incubation. Red and blue arrows respectively denote the decrease/increase of the red/blue cluster absorbance and emission intensity with time. The inset (b) shows a magnified wavelength region in 580–720 nm of the emission spectra. (c) TEM image of the blue-emitting silver nanocluster while its inset shows HRTEM image with size histogram of corresponding silver nanocluster. (d) MALDI-mass spectra of BSA and BSA-containing blue-emitting silver nanocluster synthesized from Ag₁₃NCs.Moreover, the atomic composition of the NCs can be also be estimated from the Jellium model using the equation^38,39E_em = E_Fermi/N^0.33where E_Fermi is the Fermi energy of the metal (Ag), E_em is the emission energy of the MNCs and N is the number of atoms constituting a MNC. Using the model equation, the number of silver atoms for the blue-emitting AgNCs can be predicted as 8.45 (∼8) Ag atoms which is a good agreement with our MALDI data (8 Ag atoms). However, the theoretical calculation estimated as N ∼ 24 for the red-emitting AgNCs, which is not in agreement with the MALDI data (13 Ag atoms). This is because of the well-known deviation of the Jellium model for higher number of Ag atoms in AgNCs because of increase in the electronic screening effects and the harmonic distortion in the potential energy well.¹⁹Although the red-emitting cluster is not very stable at the experimental condition (pH 11.5, 37 °C), it may be easily stabilized by lowering the temperature or pH. The fluorescence intensity of the red-emitting and blue-emitting cluster kept at 4 °C, was almost preserved for more than 15 days (Fig. S8^†). On the other hand, lowering the pH to 6, also inhibits the red to blue-cluster transformation (Fig. S9^†). The observations indicate that the red-blue transformation has a moderate activation barrier and the conversion may be governed by the change in the structure of the protein in the alkaline condition. Acidification of the solution can stop the transformation of the protein conformation and inhibits the process.From these observations, we may conclude that the conversion from NPs to NCs occurs in two steps. First, a rapid dissolution of AgNP occurs in the alkaline medium. The kinetics of the dissolution process can be monitored through a time-dependent decrease of the SPR band and the time constant was found to be ∼13 min (Fig. S10^†). Dissolution of AgNPs is an important issue and assumed to be the leading cause of toxicity of AgNPs in biological mediums.⁴⁰ The dissolution is commonly favored at a low pH but drastically inhibited at high pH.⁴¹ The swift dissolution of the BSA-protected AgNP observed here at a high pH (11.5) is unprecedented. Thus, the BSA capping may have an active role in the dissolution process. We comprehend that the oxidation power of protein may be activated in the basic medium.Organothiols (R-SH) are known to promote dissolution of AgNPs; R-SH progressively reacts with Ag atoms to form RS-Ag complex.⁴² Since cysteine is also an organothiol, it is expected to play an essential role in the dissolution of AgNPs. Gondikas et al. showed that excess cysteine could favor the dissolution process of AgNPs, whereas another amino acid, serine (S–H bond is replaced by O–H bond), has no effect.⁴³ Zang and coworkers showed that only the isolated or reduced cysteine in a protein has a dominant role in the dissolution of NPs.⁴⁴ Although BSA contains as many as 35 cysteine residues; 34 of them are involved in S–S bond formation and only a single cysteine is present in free form (S–H). Hence, the dissolution of AgNPs at neutral pH may be negligible.Most proteins rich in sulfur-containing residues (cysteine and methionine) may degrade in alkaline solution. Florence reported that about 5 of 17 S–S bridges in BSA may be cleaved in the presence of 0.2 M NaOH.⁴⁵ Thus, at higher pH, some disulfide bonds may be cleaved and more cysteine residues may participate in the dissolution of BSA-capped AgNPs.In the second step, Ag⁺ ions generated from the dissolution of AgNPs, can be reduced either by the protein capping itself or by an external reducing agent to form NCs (Scheme 1). The tyrosine residues may be responsible for the reduction of the metal ions to NCs.^25,33 At a pH, higher than the pKa (10.46) of tyrosine, the reduction capability of tyrosine is enhanced by deprotonation of the phenolic group.^25,33,46 Moreover, the addition of a strong reducing agent (e.g., NaBH₄) may lead to a faster reduction, which favors quicker nucleation and growth of Ag atoms forming the bigger NCs (Ag₁₃NCs). However, the large Ag₁₃NCs may not be adequately stabilized by the protein conformation at that condition and hence may transform into the more stable blue-emitting Ag₈NCs.Open in a separate windowScheme 1Schematic representation of the transformation of the BSA-capped AgNPs to blue- and red-emitting AgNCs.The conformation change of the protein capping during the conversion was also supported by the circular dichroism (CD) measurements (Fig. S11^†). The formation of AgNPs results in a negligible change in the protein conformation (Table S3^†). However, the formation of red Ag₁₃ cluster results in a substantial modification in the BSA conformation. The α helix content reduces from 57% to 49%, whereas coil randomness increases from 17% to 21% without a major change in the β sheet. Interestingly, blue-emitting Ag₈ cluster perturbed the conformation of the BSA to a much larger extent (Table S3^†). As the cysteine disulfide bond has a direct role on maintaining the folded conformation of BSA, its breaking may change the protein conformation. The addition of NaOH induces breaking of S–S bond, which leads to formation of AgNCs with subsequent change in protein secondary structure.In conclusion, we report an unprecedented fast dissolution of AgNPs through activation of the protein (BSA) capping by elevating the pH of the medium to 11.5. At higher pH, the disulfide bonds may be cleaved, and the free cysteine may activate the dissolution process. The protein capping also plays a crucial role in the formation of fluorescent nanocluster after the completion of the dissolution process. Thus, we explored multiple roles of the BSA capping – (1) a stable capping agent at neutral pH to stabilize the AgNPs (2) activates the dissolution process probably via oxidative dissolution of the AgNPs (3) adsorbing the nascent silver ions within its scaffold and (4) finally reducing them to fluorescent nanocluster.     

Electro-Mechanical Finger Prosthesis: A Novel Approach for Rehabilitation of Finger Amputees

Prosthesis refers to artificial replacement of an absent part of the human body. These prostheses help in psychological support of the patients and enhance their social acceptance. Complete or partial finger amputations are some of most frequently encountered forms of partial hand loss. Micro vascular reconstruction is the first choice of rehabilitation but when it is contraindicated, unavailable, unsuccessful or unaffordable, the prosthetic rehabilitation is an alternative for improving the psychological status of an individual. Most of these artificial prostheses make use of silicone. The present paper tries to combine aesthetics with function. The authors have created functionally active finger prosthesis with the help of electromechanical controls. The prosthesis is battery-powered, light-weight, and allows the user to regain complete control of flexion and extension movements of an artificial finger.

     

Food poisoning associated methemoglobinemia: Time to wake up

Dear editor,With interest we read the recent article on methemoglobinemia by Chan et al.[1]Through this letter,we would like to add few additional comments regarding methemoglobinemia and its relevance in medicine practice with regards to food poisoning.While Chan et al[1]successfully managed their patient of methemoglobinemia and could pinpoint choy sum as the responsible agent,we wonder if there were any more cases of choy sum related to methemoglobinemia detected at the same time in the community?