Evaluating the Respiratory Support Pattern and Relationship with Initial Oxygen Saturation of the COVID Isolation Unit Patients in Sylhet.

COVID-19 is the devastating pandemic of the century predominantly fatal due to its respiratory failure nature. Severe and critical patients need oxygen supplementation in different forms. This cross-sectional study was conducted in four tertiary hospitals of Sylhet, Bangladesh from November 2020 to March 2021. All the patients admitted in the COVID-19 isolation units and fulfill the selection criterion were enrolled in this study. The primary objective of this study was to evaluate different types of respiratory supports and its relationship with initial oxygen saturation (SpO2). Total 481 patients were enrolled. There was a male predominance (65.00%) in the participants. Highest number of participants was from 61-70 years age group. Number of ventilated patients were significantly high (p<0.001) in the COVID-19 patient group. The initial SpO2 and hospital staying period of COVID-19 positive and negative group did not show any significant difference but these two parameters showed significant difference among died and survived group (p<0.001). Nearly one fourth patients (24.94%) of total patients were treated in ICU with high flow nasal cannula (HFNC), non-invasive ventilation (NIV) and mechanical ventilation. Among the ICU admitted patients nearly one-fourth (24.16%) patients were treated with mechanical ventilation. Mortality rate was 62.00% for ventilated patients, 70.60% for NIV patients and 15.80% for the HFNC patients.

De-ubiquitinases on the move: an emerging field in plant biology.

A balance between the synthesis and degradation of active proteins governs diverse cellular processes in plants, spanning from cell-cycle progression and circadian rhythm to the outcome of several hormone signalling pathways. Ubiquitin-mediated post-translational modification determines the degradative fate of the target proteins, thereby altering the output of cellular processes. An equally important, and perhaps under-appreciated, aspect of this pathway is the antagonistic process of de-ubiquitination. De-ubiquitinases (DUBs), a group of processing enzymes, play an important role in maintaining cellular ubiquitin homeostasis by hydrolyzing ubiquitin poly-proteins and free poly-ubiquitin chains into mono-ubiquitin. Further, DUBs rescue the cellular proteins from 26S proteasome-mediated degradation to their active form by cleaving the poly-ubiquitin chain from the target protein. Any perturbation in DUB activity is likely to affect proteostasis and downstream cellular processes. This review illustrates recent findings on the biological significance and mechanisms of action of the DUBs in Arabidopsis thaliana, with an emphasis on ubiquitin-specific proteases (UBPs), the largest family among the DUBs. We focus on the putative roles of various protein-protein interaction interfaces in DUBs and their generalized function in ubiquitin recycling, along with their pre-eminent role in plant development.

Intracranial spread of IgG4-related disease via skull base foramina.

IgG4-related disease (IgG4-RD) is a newly recognised, multiorgan, inflammatory disease, and its full clinical spectrum remains undefined. We present a biopsy-proven case of IgG4-RD presenting with a parapharyngeal mass with intracranial extension and possible involvement of the brain parenchyma. We highlight the importance of considering the diagnosis in those presenting with tumefactive lesions, leptomeningitis or pachymeningitis and emphasise the value of securing a tissue diagnosis so that appropriate long-term treatment can be instigated and complications avoided.

Selection of superior lentil (Lens esculenta M.) genotypes by assessing character association and genetic diversity.

Lentil is one of the most important pulse crops in the world as well as in Bangladesh. It is now considered a main component for training and body building practising in first world countries. Yield varies tremendously from year to year and location to location. Therefore, it is very important to find genotypes that perform consistently well even in ecological farming systems without any intercultural operations. Twenty lentil genotypes were tested during the period from November 2010 to March 2011 and from December 2011 to March 2012 with three replicates in each season to determine genetic variability, diversity, characters association, and selection indices for better grain yield. The experiment was conducted at the breeding field of the Department of Genetics and Plant Breeding, Bangladesh Agricultural University, Mymensingh. This study revealed that all the genotypes possess a high amount of genetic diversity. Plant height and 100-grain weight showed significant positive correlation with grain yield plant(-1) that was also confirmed by path analysis as the highest direct effect on grain yield. The genotypes BM-513 and BM-941 were found to be the best performer in both the seasons and were considered as consistent genotype. The genotypes were grouped into four clusters based on Euclidean distance following Ward's method and RAPD analysis. However, discriminant function analysis revealed a progressive increase in the efficiency of selection and BM-70 ranked as the best followed by the genotypes BM-739, BM-680, BM-185, and BM-513. These genotypes might be recommended for farmers' cultivation in ecological farming in Bangladesh.

FIP1L1-PDGFRA positive chronic eosinophilic leukaemia and associated central nervous system involvement.

Interstitial deletion involving chromosome 4q12 generates the novel tyrosine kinase fusion protein encoded by FIP1L1-PDGFRA, which is present in many patients previously labelled as having hypereosinophilic syndrome, initially reported in 2003. Reports in recent literature document excellent clinical and molecular response to the tyrosine kinase inhibitor imatinib (Glivec). This report describes the case of a 58-year-old lady, diagnosed with FIP1L1-PDGFRA positive hypereosinophilic disorder, who subsequently developed symptoms related to an intracranial lesion. Biopsy and molecular genetic studies confirmed a diffuse infiltrative lesion, with evidence of FIP1L1-PDGFRA gene fusion. Initiation of imatinib treatment led to impressive clinical and radiological response.

Observations of hepatic encephalopathy profile in a tertiary care centre.

A study was conducted among 67 patients presenting with hepatic encephalopathy to establish the aetiological diagnosis and record the incidence of acute and chronic liver diseases. They all had undergone thorough clinical and laboratory evaluation. The factor precipitating encephalopathy was also identified. Among 67 patients 19 (28.4%) had acute liver disease and 48 (71.6%) had chronic liver disease. Majority of patients had grade 2 encephalopathy at presentation. Among the acute cases most common aetiology was acute viral hepatitis due to hepatitis B and E viruses whereas alcoholic liver disease was the most frequent cause of chronic liver disease. The most common precipitating factor was gastro-intestinal haemorrhage.

Population based mortality and quality of death certification in progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome).

OBJECTIVE: To estimate the mortality of progressive supranuclear palsy (PSP) and to assess the quality of death certification in patients with PSP who died in England and Wales. METHODS: An analysis was conducted of ICD-9 (International Classification of Diseases, version 9) coded deaths obtained through the Office of National Statistics over an eight year period. RESULTS: The crude annual mortality rate was 1.77 (95% confidence interval, 1.64 to 1.90) cases per million, using the mid-1996 population estimate for England and Wales. Annual mortality increased over time, possibly as a result of increased incidence or increased awareness of the disorder. Forty nine death certificates from deceased patients previously diagnosed clinically showed that the commonest proximate cause of death was pneumonia, occurring in 45% of cases (22/49). The underlying cause of death was cited as pneumonia in 14% of cases (7/49). PSP was mentioned in only 65% of death certificates (32/49). Eight of the 49 cases (16%) underwent necropsy and results were available for five of these cases. PSP was confirmed pathologically in four; the remaining case was diagnosed as Parkinson's disease. CONCLUSIONS: Further research is needed to establish the reasons for the observed increase in mortality. Determining the population mortality rate for PSP using the ICD-9 coding system is problematic but is likely to improve following the introduction of ICD-10 updated codes and coding rules.

Clinical features and natural history of progressive supranuclear palsy: a clinical cohort study.

OBJECTIVE: To describe clinical features and identify prognostic predictors in progressive supranuclear palsy (PSP). METHODS: Record-based diagnosis according to National Institute of Neurological Disorders and Stroke-Society for Progressive Supranuclear Palsy criteria was performed in 187 cases of PSP. Clinical information was abstracted from patient records. Sixty-two patients (33%) were examined by the investigators. Forty-nine of 62 patients (79%) underwent standardized clinical assessment. Predictors of survival were examined after a mean of 6.4 years. RESULTS: The most common symptoms at disease onset related to mobility (69%). Of patients undergoing standardized clinical assessment, diplopia occurred in 61%, photophobia in 43%, and eyelid apraxia in 43%. Seventy-five cases (40%) died during follow-up. Older age at onset and classification as probable PSP were associated with poorer survival. Onset of falls (hazard ratio 3.28, 95% CI 1.17 to 9.13), speech problems (hazard ratio 4.74, 95% CI 1.10 to 20.4), or diplopia (hazard ratio 4.23, 95% CI 1.23 to 14.6) within 1 year and swallowing problems within 2 years (hazard ratio 3.91, 95% CI 1.39 to 11.0) were associated with a worse prognosis. CONCLUSIONS: Mobility problems are the commonest early feature in PSP and visual symptoms are often functionally disabling. Early falls, speech and swallowing problems, diplopia, and early insertion of a percutaneous gastrostomy predict reduced survival.

Effect of ApoE and tau on age of onset of progressive supranuclear palsy and multiple system atrophy.

In addition to allelic association between genetic polymorphisms and diseases, modulation of age of onset is a well recognised effect of disease susceptibility genes. The ApoE epsilon4 allele is associated with an earlier age of onset of sporadic and familial Alzheimer's disease. It has been suggested that the tau genotype influences the age of onset of progressive supranuclear palsy (PSP), a form of atypical parkinsonism caused by tau neurofibrillary tangle deposition. We have therefore analysed the relationship between tau and ApoE genotypes and the age of onset of PSP and another form of atypical parkinsonism, multiple system atrophy (MSA). We have not found any effect of possession of the tau H1 haplotype or the ApoE epsilon4 allele on the age of onset of MSA or PSP.

The prevalence of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) in the UK.

We performed a study to estimate the point prevalence of progressive supranuclear palsy (PSP) in the UK at national, regional and community levels. A 'Russian doll' design was used in which the population denominator for each of the three studies was successively smaller, whilst the method of case ascertainment became increasingly more rigorous. The NINDS-SPSP (National Institute of Neurological Disorders and the Society for Progressive Supranuclear Palsy) diagnostic criteria for PSP were applied throughout the study for case definition. The national study identified cases using passive referral mechanisms [e.g. the British Neurological Surveillance Unit (BNSU), PSP (Europe) Association patient register]. We identified 577 cases of PSP, giving a national prevalence estimate of 1.0 per 100 000 [95% confidence interval (CI) 0.9-1.1]. The North of England regional study used active 'multiple source' case ascertainment from a collaborative network of neurologists and non-neurologists. We identified 80 cases of PSP in this study, giving a crude and age-adjusted prevalence of 3.1 (95% CI 2.4-3.8) and 2.4 (1.9-3.0) per 100 000, respectively. Of these 80 cases, 51 patients (65%) were referred initially to non-neurologists and 10 patients (13%) had not seen a neurologist at any stage of their illness. The proportion of female cases was significantly greater in the regional than in the national study (61% versus 44%; P < 0.02). Cases referred to non-neurologists were significantly older than those referred to neurologists in the regional study (median age 73 versus 69.5 years; P < 0.01). Patients in the community study were identified via diagnostic and therapeutic registers from a representative sample of general practices in Newcastle upon Tyne. We identified 17 cases of PSP, yielding crude and age-adjusted prevalences of 6.5 (95% CI 3.4-9.7) and 5.0 (95% CI 2.5-7.5) per 100 000, respectively. Seven of the 17 cases (41%) had not previously been diagnosed as PSP. This study suggests that PSP is more common than previously considered, is commonly misdiagnosed and that the majority of cases are not initially referred to neurologists. The study also confirms the importance of active and detailed case ascertainment in ensuring reliable prevalence estimates.

The epidemiology of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome).

Progressive supranuclear palsy (PSP, also known as Steele-Richardson-Olszewski syndrome) is relatively uncommon. Studies to date have found a crude population prevalence for PSP of between 1.39 and 4.9 cases per 100,000. An increased awareness of the condition, together with recently formulated clinical diagnostic criteria, should facilitate future descriptive epidemiological studies.Possible aetiological influences both genetic (tau polymorphisms) and environmental (herbal tea and tropical fruit consumption in the French West Indies) have recently been postulated. Future studies into both disease prevalence and aetiology would benefit from a multi-centre approach.

Multiple system atrophy/progressive supranuclear palsy: alpha-Synuclein, synphilin, tau, and APOE.

Article abstract-Alpha synuclein, tau, synphilin, and APOE genotypes were analyzed in patients with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) and controls. The predisposing effect of the tau insertion polymorphism to the development of PSP is confirmed. However, no effect of alpha-synuclein, synphilin, or APOE variability on the development of PSP, or of tau, alpha-synuclein, APOE, or synphilin gene variability on the development of MSA, are demonstrated.

Multiple intermediates and transition states during protein unfolding.

Rapid kinetic studies of the unfolding of the small protein barstar by urea have been used to demonstrate the presence of at least two unfolding intermediates on two competing unfolding pathways. One intermediate has native-like secondary structure but has a partially solvated hydrophobic core, while the other is devoid of considerable secondary structure but has an intact hydrophobic core. It is shown that the transition states on the two pathways are very dissimilar structurally, but very similar energetically.

Folding of tryptophan mutants of barstar: evidence for an initial hydrophobic collapse on the folding pathway.

The contributions of the three tryptophan residues of barstar to the spectroscopic properties, stability, and folding of the protein have been studied by mutating two of the tryptophans, Trp38 and Trp44, individually as well as together, to phenylalanines, Phe. The three mutant proteins studied are shown to be similar to wt barstar in structure by activity measurements as well as by spectroscopic characterization. Fluorescence energy transfer between the tryptophans as well as quenching by their local structural environments complicates the analysis of the contributions of the individual tryptophans to the fluorescence of the wt protein, but it is demonstrated that Trp53, which is completely buried within the hydrophobic core, makes the dominant contribution to the fluorescence, while the fluorescence of Trp38 is largely quenched in the fully folded protein. GdnHCl- as well as temperature-induced equilibrium unfolding studies, using three different structural probes, indicate that W38FW44F, where both Trp38 and Trp44 have been removed, follows a two-state unfolding transition and is less stable than the wt barstar. The fluorescence-monitored folding and unfolding kinetics of W38FW44F have been studied in detail. W38FW44F folds 2-fold faster and unfolds 3-fold faster than wt barstar. A large fraction of the total fluorescence change that occurs during folding occurs in a burst phase within 4 ms after commencement of folding. A similar burst phase change in fluorescence, although to a smaller extent, is shown to occur during the folding of wt barstar. The results suggest that a very early folding intermediate accumulates within 4 ms of folding, and that this kinetic intermediate is sufficiently compact that Trp53, which is completely sequestered from solvent in the fully folded protein, is also significantly sequestered from solvent in this intermediate.

Neurological paraneoplastic syndromes.

Paraneoplastic neurological syndromes are uncommon, however, their diagnosis is of major practical importance. The identification of antibodies in the serum or cerebrospinal fluid in central nervous system paraneoplastic syndromes confirms the clinical diagnosis of a paraneoplastic syndrome and allows early identification of an underlying tumour at a stage when it is localised and more amenable to treatment. The failure to identify antibodies in patients with characteristic presentations of underlying neurological paraneoplastic syndromes does not exclude an underlying cancer. Necrotising myelopathy, dermatomyositis, and chronic inflammatory demyelinating polyneuropathy all occur more frequently than expected in patients with cancer but autoantibodies have not yet been identified. Although significant advances have been made in diagnosis, further research is needed in the detection of autoantibodies and the elucidation of their role in the aetiology of neurological disease.

Motional dynamics of a buried tryptophan reveals the presence of partially structured forms during denaturation of barstar.

A double mutant of the single-domain protein barstar having a single tryptophan (W53) was made by mutating the remaining two tryptophans (W38 and W44) into phenylalanines. W53 is buried in the core of barstar. Time-resolved fluorescence of the mutant barstar (W38FW44F) showed that W53 has a single fluorescence lifetime in the native (N) state and has three lifetimes in the molten globule-like low-pH (A) form. Quenching of fluorescence by either KI or acrylamide showed that W53 is solvent inaccessible in the N-state and fairly accessible in the A-form. The denaturation of W38FW44F by guanidine hydrochloride (GdnHCI) was monitored by several probes: near-UV and far-UV circular dichroism (CD), fluorescence intensity, and steady-state and time-resolved fluorescence anisotropy. While the unfolding transitions observed through CD and fluorescence intensity coincided with each other (midpoint approximately 1.8 M GdnHCI), the transition observed through the steady-state fluorescence anisotropy was markedly different from others. Initially, the anisotropy increased with the increase in the concentration of GdnHCI and decreased subsequently. The midpoint of this titration was 2.2 M GdnHCI. Picosecond time-resolved fluorescence anisotropy showed that W38FW44F has a single rotational correlation time of 4.1 ns in the native (N) state and 1.5 as in the unfoled (U) state (6 M GdnHCI). These could be explained as being due to the absence of motional freedom of W53 in the N-state and the presence of rotational freedom in the U-state. In the intermediate concentration region (1.8-3.0 M GdnHCI), the anisotropy decays showed at least two coorrelation times, approximately 1 and 6-12 ns. These two correlation times are ascribed to partially structured forms leading to hindered rotation of W53. Thus, the usefulness of time-resolved fluorescence anisotropy in detecting partially folded structures is demonstrated.

pH dependence of the stability of barstar to chemical and thermal denaturation.

Equilibrium unfolding of barstar with guanidine hydrochloride (GdnHCl) and urea as denaturants as well as thermal unfolding have been carried out as a function of pH using fluorescence, far-UV and near-UV CD, and absorbance as probes. Both GdnHCl-induced and urea-induced denaturation studies at pH 7 show that barstar unfolds through a two-state F<->U mechanism and yields identical values for delta GU, the free energy difference between the fully folded (F) and unfolded (U) forms, of 5.0 +/- 0.5 kcal.mol-1 at 25 degrees C. Thermal denaturation of barstar also follows a two-state F<->U unfolding transition at pH 7, and the value of delta GU at 25 degrees C is similar to that obtained from chemical denaturation. The pH dependence of denaturation by GdnHCl is complex. The Cm value (midpoint of the unfolding transition) has been used as an index for stability in the pH range 2-10, because barstar does not unfold through a two-state transition on denaturation by GdnHCl at all pH values studied. Stability is maximum at pH 2-3, where barstar exists in a molten globule-like form that forms a large soluble oligomer. The stability decreases with an increase in pH to 5, the isoelectric pH of the protein. Above pH 5, the stability increases as the pH is raised to 7. Above pH 8, it again decreases as the pH is raised to 10. The decrease in stability from pH 7 to 5 in wild-type (wt) barstar, which is shown to be characterized by an apparent pKa of 6.2 +/- 0.2, is not observed in H17Q, a His 17-->Gln 17 mutant form of barstar. This decrease in stability has therefore been correlated with the protonation of His 17 in barstar. The decrease in stability beyond pH 8 in wt barstar, which is characterized by an apparent pKa of 9.2 +/- 0.2, is not detected in BSCCAA, the Cys 40 Cys 82-->Ala 40 Ala 82 double mutant form of barstar. Thus, this decrease in stability has been correlated with the deprotonation of at least one of the two cysteines present in wt barstar. The increase in stability from pH 5 to 3 is characterized by an apparent pKa of 4.6 +/- 0.2 for wt barstar and BSCCAA, which is similar to the apparent pKa that characterizes the structural transition leading to the formation of the A form. The use of Cm as an index of stability has been supported by thermal denaturation studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Perturbation of a tertiary hydrogen bond in barstar by mutagenesis of the sole His residue to Gln leads to accumulation of at least one equilibrium folding intermediate.

A specific tertiary hydrogen bond that is present between the side-chain hydroxyl group of Tyr30 and the side-chain N delta 1 atom of His17 in the small, monomeric, single-domain protein, barstar, has been perturbed by site-directed mutagenesis of the sole histidine residue (His17) to a glutamine residue. The effect of the perturbation has been studied in the resultant mutant protein, H17Q, by equilibrium unfolding methods. Both guanidine hydrochloride (GdnHCl)-induced denaturation and thermal denaturation studies have been performed, with unfolding monitored by UV absorption, intrinsic tryptophan fluorescence, near-UV and far-UV circular dichroism (CD), and size exclusion chromatography. While wild-type (wt) barstar shows a two-state unfolding transition when denatured by either GdnHCl or heat, the mutant protein H17Q undergoes unfolding through a transition that involves at least one equilibrium intermediate I, which is populated at intermediate concentrations of denaturant or at intermediate temperatures. In the case of GdnHCl-induced denaturation, the midpoint of the fluorescence-monitored denaturation curve is 1.4 +/- 0.1 M, that of the near-UV CD-monitored denaturation curve is 1.6 +/- 0.1 M, and that of the far-UV CD-monitored denaturation curve is 1.8 +/- 0.1 M. The accumulation of I is also evident in gel filtration experiments which indicate that I forms slowly from the fully-folded form, F, and that once formed, I rapidly equilibrates with the unfolded form, U. The gel filtration data for H17Q suggest that in 1.5 M GdnHCl, there is no F present and that I is the predominant form. I does not appear to possess hydrated hydrophobic surfaces, which is reflected in its inability to bind 8-anilino-1-naphthalenesulfonic acid (ANS). At least one equilibrium-unfolding intermediate is also observed upon thermal denaturation. The midpoints of the thermal denaturation curves of H17Q are 63.0 +/- 0.5 degrees C when monitored by absorbance at 287 nm or by intrinsic fluorescence at 332 nm; 65.0 +/- 0.5 degrees C when monitored by mean residue ellipticity at 275 nm; and 68.3 +/- 0.5 degrees C when monitored by mean residue ellipticity at 220 nm. In contrast, all four optical probes yield the same midpoint, 71.5 +/- 0.5 degrees C, for the wt protein. The results indicate that perturbation of the tertiary hydrogen bond leads to the accumulation of at least one intermediate (I) in both thermal denaturation studies and GdnHCl-induced denaturation studies. The intermediate(s) I are characterized by a greater disruption of tertiary structure than of secondary structure.