Cross-cultural adaptation and validation of the Neck Bournemouth Questionnaire into Urdu language.

BACKGROUND: The Neck Bournemouth Questionnaire (NBQ) has been translated and validated in a number of languages and has good psychometric properties for assessing neck pain. However, an Urdu translation is currently unavailable. PURPOSE: To translate, cross-culturally adapt, and validate the NBQ into Urdu language (NBQ-U) in patients with nonspecific neck pain (NSNP). METHODS: The NBQ was translated and cross-culturally adapted into Urdu using previously described guidelines. The study included 150 Urdu-speaking patients with NSNP and 50 healthy participants. All participants completed the NBQ-U, Urdu version of neck disability index (NDI-U), neck pain and disability scale (NPDS), and numerical pain rating scale (NPRS). After three weeks of physical therapy treatment, the patients completed all of the above-mentioned questionnaires, along with the global rating of change scale. Reliability, validity, and responsiveness were all tested. RESULTS: The NBQ-U demonstrated excellent test-retest reliability (intra-class correlation coefficient = 0.92) and high internal consistency (Cronbach's alpha = 0.89). The NBQ-U showed moderate to strong correlations with NDI-U, NPDS, and NPRS (r = 0.67-0.73, P < .001). The results revealed a significant difference between patients and healthy controls in the NBQ-U total scores (P < .001). The NBQ-U has a single factor structure with no floor or ceiling effects for individual item scores or total scores. A significant difference in the NBQ-U change scores between the stable and the improved groups (P < .001) confirmed its responsiveness. Furthermore, the NBQ-U change score showed moderate correlations with NDI-U, NPDS, and NPRS change scores (r = 0.52-0.62, P < .001). CONCLUSION: In Urdu-speaking patients with NSNP, the NBQ-U demonstrated good reliability, validity, and responsiveness.

Redox conditions correlated with vibronic coupling modulate quantum beats in photosynthetic pigment-protein complexes.

Quantum coherences, observed as time-dependent beats in ultrafast spectroscopic experiments, arise when light-matter interactions prepare systems in superpositions of states with differing energy and fixed phase across the ensemble. Such coherences have been observed in photosynthetic systems following ultrafast laser excitation, but what these coherences imply about the underlying energy transfer dynamics remains subject to debate. Recent work showed that redox conditions tune vibronic coupling in the Fenna-Matthews-Olson (FMO) pigment-protein complex in green sulfur bacteria, raising the question of whether redox conditions may also affect the long-lived (>100 fs) quantum coherences observed in this complex. In this work, we perform ultrafast two-dimensional electronic spectroscopy measurements on the FMO complex under both oxidizing and reducing conditions. We observe that many excited-state coherences are exclusively present in reducing conditions and are absent or attenuated in oxidizing conditions. Reducing conditions mimic the natural conditions of the complex more closely. Further, the presence of these coherences correlates with the vibronic coupling that produces faster, more efficient energy transfer through the complex under reducing conditions. The growth of coherences across the waiting time and the number of beating frequencies across hundreds of wavenumbers in the power spectra suggest that the beats are excited-state coherences with a mostly vibrational character whose phase relationship is maintained through the energy transfer process. Our results suggest that excitonic energy transfer proceeds through a coherent mechanism in this complex and that the coherences may provide a tool to disentangle coherent relaxation from energy transfer driven by stochastic environmental fluctuations.

Clinical and Histopathological Variables and Prognostic Factors of Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is a rare and highly aggressive tumor with a poor prognosis. The literature on prognosis from low-income or low-middle-income countries is limited and scarce. This study aimed to determine the clinical and histopathological characteristics, recurrence-free survival (RFS), overall survival (OS), and the factors affecting ACC's prognosis. This was a retrospective study of patients that presented with ACC to the Shaukat Khanum Memorial Cancer & Research Center, Lahore, Pakistan, between January 2011 and May 2018. Information regarding demographics and clinical and histopathological variables were extracted and analyzed. Of the 25 subjects, 16 (64%) were female. The median age of the sample was 35 years (range; 21 - 72 years). Statistically significant associations were found between RFS and functional status of the tumor (p = 0.014), cortisol overproduction (p = 0.02), androgen excess (testosterone [p = 0.03] and dehydroepiandrosterone sulfate [DHEA SO4] [p = 0.004]), Ki-67 score (p = 0.03), mitotic rate (p = 0.02), stratified mitotic rate (p = 0.01), and composite variable of disease (p = 0.004). The OS was found to have statistical associations with cortisol hypersecretion (p = 0.02), DHEA SO4 excess (p = 0.01), Modified Weis Score (p < 0.001), mitotic rate (p = 0.02), stratified mitotic rate (p = 0.003), and composite variable of disease (p = 0.001). Linear regression (forward-type) analysis suggested that the functional status of the tumor and the disease recurrence index statistically predicted the variance in RFS and OS, respectively. Multiple clinical and histopathological variables appear to affect the prognosis of ACC. However, based on multivariable analysis, it appears that the functional status of the tumor and the composite variable of disease recurrence are predictors of RFS and OS, respectively.

Photosynthesis tunes quantum-mechanical mixing of electronic and vibrational states to steer exciton energy transfer.

Photosynthetic species evolved to protect their light-harvesting apparatus from photoxidative damage driven by intracellular redox conditions or environmental conditions. The Fenna-Matthews-Olson (FMO) pigment-protein complex from green sulfur bacteria exhibits redox-dependent quenching behavior partially due to two internal cysteine residues. Here, we show evidence that a photosynthetic complex exploits the quantum mechanics of vibronic mixing to activate an oxidative photoprotective mechanism. We use two-dimensional electronic spectroscopy (2DES) to capture energy transfer dynamics in wild-type and cysteine-deficient FMO mutant proteins under both reducing and oxidizing conditions. Under reducing conditions, we find equal energy transfer through the exciton 4-1 and 4-2-1 pathways because the exciton 4-1 energy gap is vibronically coupled with a bacteriochlorophyll-a vibrational mode. Under oxidizing conditions, however, the resonance of the exciton 4-1 energy gap is detuned from the vibrational mode, causing excitons to preferentially steer through the indirect 4-2-1 pathway to increase the likelihood of exciton quenching. We use a Redfield model to show that the complex achieves this effect by tuning the site III energy via the redox state of its internal cysteine residues. This result shows how pigment-protein complexes exploit the quantum mechanics of vibronic coupling to steer energy transfer.

Malignancy rates in thyroid nodules classified as Bethesda categories III and IV; a subcontinent perspective.

BACKGROUND: Bethesda category III and IV thyroid nodules fall in the indeterminate risk of malignancy category. These nodules have been a relatively elusive entity to manage as previous studies have shown a wide variation in malignancy rates in different regions and institutions across the world. However, data from the subcontinent with regards to this is scarce. AIM AND OBJECTIVE: This study aimed to determine the characteristics and malignancy rates of cytology proven Bethesda Category III and IV thyroid nodules and its association with clinical, histopathological and laboratory variables, in the regional population. METHOD: A retrospective search was performed on all patients with thyroid nodules who presented to this hospital, from January 2011 to September 2018. Patients who had cytology proven Bethesda category III and IV thyroid nodules that underwent surgery were included in the study. RESULTS: Malignancy in Bethesda Category III and Bethesda Category IV thyroid nodules was 29.6% and 47.1%, respectively. There was no significant association determined between malignancy rate and various clinical, histopathological, and radiological characteristics. CONCLUSION: The malignancy rates in Bethesda category III and IV thyroid nodules in this study are significantly higher than that initially suggested by the Bethesda consensus publication but is comparable to international data present.

Ectopic Acromegaly Secondary to Bronchial Tumour: A Case Report of Rare Occurrence.

Introduction: Acromegaly is caused due to the unregulated and sustained overproduction of growth hormone (GH). The majority of the cases are caused by autonomous secretion of GH from anterior pituitary tumours. Nonetheless, in <1% of the cases, the cause of autonomous secretion is secondary to ectopic GH-releasing hormone (GHRH) production. Bronchial carcinoids are the most common cause of ectopic GHRH production. Case Description: A 32-year-old female presented to the clinic with a history of cough, haemoptysis and undocumented weight loss for 4 years. Initial workup showed a large right main stem endobronchial mass. Transbronchial biopsy of the mass revealed a Grade I neuroendocrine tumour (NET). During NET workup, a large sellar mass was incidentally found on cross-sectional imaging. The hormonal profile revealed markedly elevated insulin-like growth factor-1 (IGF-1) and mildly raised prolactin. The magnetic resonance imaging (MRI) brain study revealed pituitary macroadenoma measuring 2 cm × 1.2 cm × 1.5 cm. The patient underwent bronchial carcinoid tumour resection, which led to normalisation of serum IGF-1 and GH response to an oral glucose tolerance test. Subsequent MRI brain revealed complete resolution of previously noted sellar mass. Practical Implications: This case highlights the importance of differentiating acromegaly secondary to pituitary adenoma and ectopic acromegaly. This case emphasises the importance of keeping rare entities in the differential while assessing patients with pituitary macroadenoma.

Clinical Characteristics and Outcome of Patients With Pheochromocytoma: A Single Center Tertiary Care Experience.

Objective The aim of this study was to evaluate the demographic and clinical characteristics of patients with pheochromocytoma and determine the treatment outcome with overall survival rates of patients with pheochromocytoma. Methods A retrospective, cross-sectional study was performed on all the patients with histologically proven pheochromocytoma presenting to Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH & RC) Lahore, between August 2006 and July 2018. Clinical, biochemical and radiological data were collected at presentation, post-surgery, at discharge and till the last follow-up; data was retrieved from hospital records. Cure was defined as no evidence of disease biochemically, clinically, and structurally. Results This study included 29 patients, 69% were female. The three most common symptoms were abdominal pain (51.7%), hypertension (44.8%) and headache (41.4%). Most pheochromocytomas were sporadic (82.8%), all were adrenal gland tumors, and 89.7% were unilateral. All patients underwent adrenalectomy. Open adrenalectomy was performed in 25 patients whereas four underwent laparoscopic adrenalectomy. Fifteen patients experienced postoperative complications. The most frequently documented intraoperative complication was hypotension. Death occurred in two patients, one patient died of metastatic disease secondary to malignant pheochromocytoma and the other patient died from perioperative complications. Cure was documented biochemically and/or radiologically in 96.5% patients. Conclusions Abdominal pain was predominant presenting feature most likely due to large tumor size. Most patients presenting to SKMCH & RC, had large intra-abdominal tumors with high cure rate. Mortality was low despite high rate of perioperative complications.

DNA scaffold supports long-lived vibronic coherence in an indodicarbocyanine (Cy5) dimer.

Vibronic coupling between pigment molecules is believed to prolong coherences in photosynthetic pigment-protein complexes. Reproducing long-lived coherences using vibronically coupled chromophores in synthetic DNA constructs presents a biomimetic route to efficient artificial light harvesting. Here, we present two-dimensional (2D) electronic spectra of one monomeric Cy5 construct and two dimeric Cy5 constructs (0 bp and 1 bp between dyes) on a DNA scaffold and perform beating frequency analysis to interpret observed coherences. Power spectra of quantum beating signals of the dimers reveal high frequency oscillations that correspond to coherences between vibronic exciton states. Beating frequency maps confirm that these oscillations, 1270 cm-1 and 1545 cm-1 for the 0-bp dimer and 1100 cm-1 for the 1-bp dimer, are coherences between vibronic exciton states and that these coherences persist for ∼300 fs. Our observations are well described by a vibronic exciton model, which predicts the excitonic coupling strength in the dimers and the resulting molecular exciton states. The energy spacing between those states closely corresponds to the observed beat frequencies. MD simulations indicate that the dyes in our constructs lie largely internal to the DNA base stacking region, similar to the native design of biological light harvesting complexes. Observed coherences persist on the timescale of photosynthetic energy transfer yielding further parallels to observed biological coherences, establishing DNA as an attractive scaffold for synthetic light harvesting applications.

Orientational Dynamics of Transition Dipoles and Exciton Relaxation in LH2 from Ultrafast Two-Dimensional Anisotropy.

Light-harvesting complexes in photosynthetic organisms display fast and efficient energy transfer dynamics, which depend critically on the electronic structure of the coupled chromophores within the complexes and their interactions with their environment. We present ultrafast anisotropy dynamics, resolved in both time and frequency, of the transmembrane light-harvesting complex LH2 from Rhodobacter sphaeroides in its native membrane environment using polarization-controlled two-dimensional electronic spectroscopy. Time-dependent anisotropy obtained from both experiment and modified Redfield simulation reveals an orientational preference for excited state absorption and an ultrafast equilibration within the B850 band in LH2. This ultrafast equilibration is favorable for subsequent energy transfer toward the reaction center. Our results also show a dynamic difference in excited state absorption anisotropy between the directly excited B850 population and the population that is initially excited at 800 nm, suggesting absorption from B850 states to higher-lying excited states following energy transfer from B850*. These results give insight into the ultrafast dynamics of bacterial light harvesting and the excited state energy landscape of LH2 in the native membrane environment.

Redox Conditions Affect Ultrafast Exciton Transport in Photosynthetic Pigment-Protein Complexes.

Pigment-protein complexes in photosynthetic antennae can suffer oxidative damage from reactive oxygen species generated during solar light harvesting. How the redox environment of a pigment-protein complex affects energy transport on the ultrafast light-harvesting time scale remains poorly understood. Using two-dimensional electronic spectroscopy, we observe differences in femtosecond energy-transfer processes in the Fenna-Matthews-Olson (FMO) antenna complex under different redox conditions. We attribute these differences in the ultrafast dynamics to changes to the system-bath coupling around specific chromophores, and we identify a highly conserved tyrosine/tryptophan chain near the chromophores showing the largest changes. We discuss how the mechanism of tyrosine/tryptophan chain oxidation may contribute to these differences in ultrafast dynamics that can moderate energy transfer to downstream complexes where reactive oxygen species are formed. These results highlight the importance of redox conditions on the ultrafast transport of energy in photosynthesis. Tailoring the redox environment may enable energy transport engineering in synthetic light-harvesting systems.

Communication: Broad manifold of excitonic states in light-harvesting complex 1 promotes efficient unidirectional energy transfer in vivo.

In photosynthetic organisms, the pigment-protein complexes that comprise the light-harvesting antenna exhibit complex electronic structures and ultrafast dynamics due to the coupling among the chromophores. Here, we present absorptive two-dimensional (2D) electronic spectra from living cultures of the purple bacterium, Rhodobacter sphaeroides, acquired using gradient assisted photon echo spectroscopy. Diagonal slices through the 2D lineshape of the LH1 stimulated emission/ground state bleach feature reveal a resolvable higher energy population within the B875 manifold. The waiting time evolution of diagonal, horizontal, and vertical slices through the 2D lineshape shows a sub-100 fs intra-complex relaxation as this higher energy population red shifts. The absorption (855 nm) of this higher lying sub-population of B875 before it has red shifted optimizes spectral overlap between the LH1 B875 band and the B850 band of LH2. Access to an energetically broad distribution of excitonic states within B875 offers a mechanism for efficient energy transfer from LH2 to LH1 during photosynthesis while limiting back transfer. Two-dimensional lineshapes reveal a rapid decay in the ground-state bleach/stimulated emission of B875. This signal, identified as a decrease in the dipole strength of a strong transition in LH1 on the red side of the B875 band, is assigned to the rapid localization of an initially delocalized exciton state, a dephasing process that frustrates back transfer from LH1 to LH2.

Complete excision of large invasive retroperitoneal paraganglioma mislabelled as hypertrophic obstructive cardiomyopathy.

Paraganglioma originates from chromaffin cells of adrenal medulla and autonomic paraganglia, which are derived from the neural crest cells. Paragangliomas are half as common as pheochromocytomas with 69% occurring in head and neck, 22% in abdomen and pelvis and 10% in the thorax. About 70% paragangliomas are sporadic, 30% are hereditary, having identifiable germline mutations of Succinate Dehydrogenase enzyme (SDH).