Intrinsically synthesized melatonin in mitochondria and factors controlling its production.

The percentage of the total amount of melatonin produced in vertebrates that comes from the pineal is small (likely <5%) but, nevertheless, functionally highly noteworthy. The significance of pineal melatonin is that it is secreted cyclically such that it has a critical function in influencing not only the suprachiasmatic nucleus but clock genes that reside in perhaps every cell throughout the organism. Extrapineal melatonin, which may be synthesized in the mitochondria of all other cells in much larger amounts than that in the pineal gland has a different function than that derived from the pineal gland. Its synthesis is not circadian and it is not directly impacted by the photoperiodic environment. Also, melatonin from the extrapineal sites is not normally secreted into the blood stream; rather, it acts locally in its cell of synthesis or, possibly via paracrine mechanisms, on immediately adjacent cells. The functions of extrapineal melatonin include central roles in maintaining molecular and redox homeostasis and actions in resisting pathological processes due to its ability to directly or indirectly detoxify free radicals. The vast majority of organisms that exist on Earth lack a pineal gland so pineal-derived melatonin is unique to vertebrates. Evidence suggests that all invertebrates, protists and plants synthesized melatonin and they have no pineal homolog; thus, the production of melatonin by extrapineal cells in vertebrates should not be unexpected. While the factors that control pineal melatonin synthesis are well documented, the processes that regulate extrapineal melatonin production are undefined.

e-Thrombosis: occupation-specific hazard in electronic information and technology professionals.

There are many known risk factors for the development of deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE). However, a recently observed risk factor is prolonged sitting (or immobility) for occupational dispensation. Some occupations, especially electronic information technology (IT) professionals, computer gamers, programmers, etc., are amenable to prolonged sitting periods for their work. Such a trend significantly increased in the corporate world during the covid pandemic restrictions and work-from-home policy of the IT companies. We have reported a case of the sudden death of an IT professional due to DVT and PTE. There is a conspicuous indication of the association between prolonged sitting hours and the development of DVT and PTE. This is also known as e-thrombosis. The prolonged seated immobility thromboembolic syndrome is a recently observed phenomenon in professionals having prolonged seated working styles. This paper is a case-based review of all tenets, i.e., clinical presentation, autopsy pathology, and preventive measures of the prolonged seated immobility thromboembolism associated with a sedentary working style.

An autopsy report with a diagnostic clinical profile on fatal overdose of life-saving iron supplement.

Ferrous sulfate is a commonly prescribed drug for prophylaxis and treatment purposes, particularly in women and adolescent girls. However, its easy availability, potential toxicity at higher doses, and vague clinical presentation make it a drug of concern when evaluating a case of poisoning. We present the case of a 28-year-old female who allegedly consumed 60 ferrous sulfate (60 mg of elemental iron in 200 mg of ferrous sulfate) tablets in a suicidal attempt. She presented with gastrointestinal disturbances on the same day to a tertiary care health facility. Investigations revealed deranged liver function tests, serum iron levels ten times the normal range, and high levels of saturated transferrin. Despite treatment, she succumbed to the poisoning 4 days after the incident. Autopsy showed features of liver failure, which was confirmed by histopathology. Chemical examination detected free ferrous and chloride ions. This fatal case of adult iron toxicity highlights the different causes of death in various stages of iron toxicity, providing a wider perspective on clinical management and aiding in the determination of the cause of death during an autopsy. This article adds a rare fatal iron poisoning case in adults to the literature, emphasizing the necessity for regulating iron tablet supplementation and raising public awareness of the toxicity of iron, which could save millions of lives.

Delivery cost of the first public sector introduction of typhoid conjugate vaccine in Navi Mumbai, India.

Navi Mumbai Municipal Corporation (NMMC), a local government in Mumbai, India, implemented the first public sector TCV campaign in 2018. This study estimated the delivery costs of this TCV campaign using a Microsoft Excel-based tool based on a micro-costing approach from the government (NMMC) perspective. The campaign's financial (direct expenditures) and economic costs (financial costs plus the monetized value of additional donated or existing items) incremental to the existing immunization program were collected. The data collection methods involved consultations with NMMC staff, reviews of financial and programmatic records of NMMC and the World Health Organization (WHO), and interviews with the health staff of sampled urban health posts (UHPs). Three UHPs were purposively sampled, representing the three dominant residence types in the catchment area: high-rise, slum, and mixed (high-rise and slum) areas. The high-rise area UHP had lower vaccination coverage (47%) compared with the mixed area (71%) and slum area UHPs (76%). The financial cost of vaccine and vaccination supplies (syringes, safety boxes) was $1.87 per dose, and the economic cost was $2.96 per dose in 2018 US dollars. Excluding the vaccine and vaccination supplies cost, the financial delivery cost across the 3 UHPs ranged from $0.37 to $0.53 per dose, and the economic delivery cost ranged from $1.37 to $3.98 per dose, with the highest delivery costs per dose in the high-rise areas. Across all 11 UHPs included in the campaign, the weighted average financial delivery cost was $0.38 per dose, and the economic delivery cost was $1.49 per dose. WHO has recommended the programmatic use of TCV in typhoid-endemic countries, and Gavi has included TCV in its vaccine portfolio. This first costing study of large-scale TCV introduction within a public sector immunization program provides empirical evidence for policymakers, stakeholders, and future vaccine campaign planning.

A Case of Fatal Non-Clostridial Gas Gangrene Following Intramuscular Injection: A Diagnostic Challenge and Dilemma at Autopsy.

Introduction: Gas Gangrene following intramuscular injection is a rare but serious condition that can lead to morbidity and mortality. This case conveys a severe and fatal complication following intramuscular injections of diclofenac and vitamin B12 in a diabetic patient. Case Report: The patient developed pain and swelling in the left buttock after the injection of vitamin B12 and Diclofenac one on each buttock which worsened over time. He was diagnosed with gas gangrene when he presented to the emergency department. The blood culture identified Klebsiella pneumonia. The patient's condition rapidly deteriorated, leading to sepsis and acute kidney injury. Despite intensive care management, the patient succumbed five days after admission. At autopsy, gas gangrene of the left lower limb was evident on external examination. Histopathological examination confirmed the acute tubular damage in the kidney and the postmortem blood culture also grew Klebsiella pneumonia and Enterobacter cloacae. The cause of death was determined to be acute tubular necrosis as a result of sepsis due to non-clostridial gas gangrene. Conclusion: This instance of gas gangrene following trivial trauma poses a challenge for the forensic pathologist in establishing the causal association and in determining the causative organism. These are important when medical/surgical intervention is in question to be the cause of a fatal infection like gas gangrene. Ante-mortem/postmortem blood culture can aid in defining the causative organism of gas gangrene but the causal association with the alleged trauma/insult is still a challenge at autopsy. This case report addresses and tries to overcome the diagnostic challenges and dilemmas at autopsy in a case of gas gangrene.

Computing of temporal information in spiking neural networks with ReRAM synapses.

Resistive switching random-access memory (ReRAM) is a two-terminal device based on ion migration to induce resistance switching between a high resistance state (HRS) and a low resistance state (LRS). ReRAM is considered one of the most promising technologies for artificial synapses in brain-inspired neuromorphic computing systems. However, there is still a lack of general understanding about how to develop such a gestalt system to imitate and compete with the brain's functionality and efficiency. Spiking neural networks (SNNs) are well suited to describe the complex spatiotemporal processing inside the brain, where the energy efficiency of computation mostly relies on the spike carrying information about both space (which neuron fires) and time (when a neuron fires). This work addresses the methodology and implementation of a neuromorphic SNN system to compute the temporal information among neural spikes using ReRAM synapses capable of spike-timing dependent plasticity (STDP). The learning and recognition of spatiotemporal spike sequences are experimentally demonstrated. Our simulation study shows that it is possible to construct a multi-layer spatiotemporal computing network. Spatiotemporal computing also enables learning and detection of the trace of moving objects and mimicking of the hierarchy structure of the biological visual cortex adopting temporal-coding for fast recognition.

Publisher Correction: Memristive neural network for on-line learning and tracking with brain-inspired spike timing dependent plasticity.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Memristive neural network for on-line learning and tracking with brain-inspired spike timing dependent plasticity.

Brain-inspired computation can revolutionize information technology by introducing machines capable of recognizing patterns (images, speech, video) and interacting with the external world in a cognitive, humanlike way. Achieving this goal requires first to gain a detailed understanding of the brain operation, and second to identify a scalable microelectronic technology capable of reproducing some of the inherent functions of the human brain, such as the high synaptic connectivity (~104) and the peculiar time-dependent synaptic plasticity. Here we demonstrate unsupervised learning and tracking in a spiking neural network with memristive synapses, where synaptic weights are updated via brain-inspired spike timing dependent plasticity (STDP). The synaptic conductance is updated by the local time-dependent superposition of pre- and post-synaptic spikes within a hybrid one-transistor/one-resistor (1T1R) memristive synapse. Only 2 synaptic states, namely the low resistance state (LRS) and the high resistance state (HRS), are sufficient to learn and recognize patterns. Unsupervised learning of a static pattern and tracking of a dynamic pattern of up to 4 × 4 pixels are demonstrated, paving the way for intelligent hardware technology with up-scaled memristive neural networks.

In vitro Antioxidant and Pharmacognostic Studies of Leaf Extracts of Cajanus cajan (L.) Millsp.

Cajanus cajan (L.) Millsp is one of the second most dietary legume crops. The leaf extracts may be used as a potential source of natural antioxidant. The ash values, extractive values, total phenolic and flavonoid content, in vitro antioxidant activity of various leaf extracts as well as anatomical investigation of Cajanus cajan were carried out. Physicochemical parameters such as total, acid-insoluble and water-soluble ash values and moisture content of the leaf powder of C. cajan were found to be 9.50%, 1.40 g/100 g, 4.15 g/100 g drug and 6.72%, respectively. Percent yield of acetone, aqueous, ethanol, ethyl acetate and chloroform leaf extracts were 9.0, 10.6, 13.75, 8.7 and 5.8 g/100 g, respectively. Significant amount of phenolic and flavonoid content were observed. The results of the antioxidant activity were found to be concentration-dependent. The IC50 values for DPPH assay determined for aqueous and ethanol extracts were 0.69 and 0.79 mg/ml, respectively. Reducing power is increased with increasing amount of concentration in both aqueous and ethanol leaf extracts. The highest hydroxyl radical scavenging activity reached up to 83.67% in aqueous and 78.75% in ethanol extracts and in phosphomolybdenum assay the aqueous extract showed strong antioxidant capacity up to 55.97 nM gallic acid equivalents/g. It was found that the aqueous extract possessed highest antioxidant activity in all the assays tested. The antioxidant characteristics of leaf extracts are possibly because of the presence of polyphenols. Microscopic study showed the presence of collenchyma, fibres, xylem, phloem, epidermis, trichomes, palisade tissue, basal sheath, pith and cortex in leaf, petiole and pulvinus.

Secondary acute myeloid leukemia after successful treatment for osteosarcoma.

Secondary acute myeloid leukemia (sAML) is a rare complication following chemotherapy for osteogenic sarcoma. However, the exact offending drug is difficult to prove as there is no consistent data. It usually develops 2 years after completion of therapy. We report a case of sAML that developed within 8 months of completing the treatment. The patient was treated with cisplatin, doxorubicin and high-dose methotreaxate followed by surgery (amputation). Eight months after completion of therapy, while on follow-up, he presented with leukocytosis and thrombocytopenia and confirmed to have AML.

Genome-wide analysis of thiourea-modulated salinity stress-responsive transcripts in seeds of Brassica juncea: identification of signalling and effector components of stress tolerance.

BACKGROUND AND AIMS: Abiotic stresses including salinity are the major constraints to crop production. In this regard, the use of thiourea (TU) in imparting salinity-stress tolerance to Indian mustard (Brassica juncea) has been demonstrated earlier. To gain an insight into the mechanism of TU action, various molecular and biochemical studies were conducted. METHODS: Microarray analysis was performed in seeds subjected to distilled water (control), 1 m NaCl, 1 m NaCl + 6·5 mm TU and 6·5 mm TU alone for 1 h. Real-time PCR validation of selected genes and biochemical studies were conducted under similar treatments at 1 h and 6 h. KEY RESULTS: The microarray analysis revealed a differential expression profile of 33 genes in NaCl- and NaCl + TU-treated seeds, most of which are established markers of stress tolerance. The temporal regulation of eight selected genes by real-time PCR indicated their early and co-ordinated induction at 1 h in NaCl + TU only. Besides, NaCl + TU-treated seeds also maintained a higher level of abscisic acid, reduced to oxidized glutathione (GSH : GSSG) ratio and activities of catalase, phenylalanine ammonia lyase and glutathione-S-transferases, as compared with that of NaCl treatment. The addition of LaCl(3) (a specific calcium-channel blocker) restricted the responses of TU both at molecular and biochemical level suggesting the possible involvement of a cytosolic calcium burst in the TU-mediated response. The TU-alone treatment was comparable to that of the control; however, it reduced the expression of some transcription factors and heat-shock proteins presumably due to the stabilization of the corresponding proteins. CONCLUSIONS: The TU treatment co-ordinately regulates different signalling and effector mechanisms at an early stage to alleviate stress even under a high degree of salinity. This also indicates the potential of TU to be used as an effective bioregulator to impart salinity tolerance under field conditions.

Thiourea modulates the expression and activity profile of mtATPase under salinity stress in seeds of Brassica juncea.

BACKGROUND AND AIMS: Large areas of the globe are becoming saline due to evapotranspiration and poor irrigation practices, and sustainability of agriculture is being seriously affected. Thiourea (TU) has been identified as an effective bioregulator imparting stress tolerance to crops. The molecular mechanisms involved in the TU-mediated response are considered in this study. METHODS: Differential display was performed in order to identify TU-modulated transcripts in Brassica juncea seeds exposed to various treatments (distilled water; 1 m NaCl; 1 m NaCl + 500 p.p.m. TU). The differential regulation of these transcripts was validated by quantitative real-time PCR. KEY RESULTS: Thiourea treatment maintained the viability of seeds exposed to NaCl for 6 h. Expression analysis showed that the transcript level of alpha, beta, gamma, delta and epsilon subunits of mitochondrial ATPase (mtATPase) varied in seeds subjected to the different treatments for 1 h: expression level was significantly altered by 1 m NaCl relative to controls; however, in the NaCl + TU treatment it reverted back in an integrated manner. Similar results were obtained from time-kinetics studies of beta and delta subunits in roots of 8-d-old seedlings. These observations were also confirmed by the mtATPase activity from isolated mitochondria. The reversal in the expression and activity profile of mtATPase through the application of a bioregulator such as TU is a novel finding for any plant system. CONCLUSIONS: The results suggest that TU treatment maintains the integrity and functioning of mitochondria in seeds as well as seedlings exposed to salinity. Thus, TU has the potential to be used as an effective bioregulator to impart salinity tolerance under field conditions, and might prove to be of high economic importance by opening new avenues for both basic and applied research.

Safety of imatinib in chronic myeloid leukemia in blastic crisis presenting as cholestatic jaundice.

Acute leukemia presenting as cholestatic jaundice is rare. It can occur due to granulocytic sarcoma compressing the bile ducts in case of acute myeloid leukemia. Rarely, diffuse infiltration of the liver sinusoids by the leukemic blasts can present as cholestatic jaundice. We report a case of chronic myeloid leukemia in lymphoid blast cell crisis presenting with severe cholestatic jaundice due to diffuse infiltration of the liver sinusoids with lymphoblasts. This patient tolerated imatinib well and, coinciding with the hematological response, there was marked reduction in the cholestasis due to blast clearance from the hepatic sinusoids. He was subsequently treated with combination chemotherapy and achieved morphological and cytogenetic remission.

UV-B exposure enhances senescence of wheat leaves: Modulation by photosynthetically active radiation.

The alterations in structure and function of photosystem II (PS II) during the senescence of primary leaves of wheat seedlings have been compared with the changes induced by ultraviolet-B (UV-B) radiation in the presence or absence of photosynthetically active radiation (PAR). The results indicated that the senescence-induced loss in pigment content, thylakoid membrane integrity and carotenoid-to-chlorophyll (Car-to-Chl) energy transfer efficiency was intensified by exposure to UV-B radiation. Different parameters for the measurement of PS II activity, such as Chl a fluorescence, O2-evolution and thermoluminescence intensity, were altered during senescence and these alterations were furthered by UV-B irradiation. The damage of photosynthetic apparatus by UV-B exposure in the presence of PAR was less than the damage in absence of PAR. The activation of molecular defense mechanisms could be a factor in the alleviation of UV-B damage in the presence of PAR.

Ultraviolet-A induced changes in photosystem II of thylakoids: effects of senescence and high growth temperature.

Ultraviolet-A (UV-A) radiation induced changes in photosystem II (PS II) of senescing leaves of wheat seedlings were investigated. UV-A radiation did not show any significant effect on the level of photosynthetic pigments. However, the decline in F(v)/F(m) and oxygen evolution rate indicated the damaging effect of the radiation on primary photochemistry of PS II. Modification at the Q(B)-binding site was inferred from the observed downshift of peak temperature of thermoluminescence (TL) B-bands. The UV-A induced changes in PS II of chloroplasts from senescing leaves were found to be synergistically accelerated by high growth temperature.

Thermoluminescence characteristics of sodium chloride salt-stressed Indian mustard seedlings.

The thermoluminescence (TL) parameters in the intact leaves and the thylakoids isolated from leaves of NaCl treated seedlings showed different patterns of change. NaCl treatment brings about a destabilization of QA and QB, leading to a decrease in Q and B bands in the leaves. However, the Q and B band intensity of isolated thylakoids increased in NaCl-treated seedlings. The differences in the TL intensities are described as the action of NaCl on the density of quinones per unit leaf area and on chlorophyll units in isolated thylakoids.

Fish oil and extruded soybeans fed in combination increase conjugated linoleic acids in milk of dairy cows more than when fed separately.

Eight multiparous Holstein and four multiparous Brown Swiss (78 +/- 43 DIM) cows were used in a 4 x 4 Latin square with 28-d periods to evaluate if feeding fish oil with a source of linoleic acid (extruded soybeans) would stimulate additional amounts of conjugated linoleic acid in milk. Four treatments consisted of a control diet with a 50:50 ratio of forage to concentrate (DM basis), a control diet with 2% added fat from either menhaden fish oil or extruded soybeans, or a combination of fish oil and extruded soybeans each adding 1% fat. DM intake (24.3, 21.6, 24.5, and 22.5 kg/d, for control, fish oil, extruded soybeans, and combination diets, respectively), milk production (32.1, 29.1,34.6, and 31.1 kg/d), and milk fat content (3.51, 2.79, 3.27, and 3.14%) were lower for cows that consumed either fish oil-containing diet, especially the 2% fish oil diet. The proportion of n-3 fatty acids in milk fat increased similarly among all three fat-supplemented diets. Concentrations of transvaccenic acid (1.00, 4.16, 2.17, and 3.51 g/100 g of fatty acids) and cis-9, trans-11 conjugated linoleic acid (0.60, 2.03, 1.16, and 1.82 g/100 g of fatty acids) in milk fat increased more with fish oil than with extruded soybeans. When fed the combination diet, these fatty acids were approximately 50% higher than expected for Holsteins, whereas concentrations were similar for Brown Swiss compared with feeding each fat source separately. These data indicated that fish oil modifies ruminal or systemic functions, stimulating increased conversion of linoleic acid into transvaccenic and conjugated linoleic acids.

Composition and flavor of milk and butter from cows fed fish oil, extruded soybeans, or their combination.

Milk was collected from eight multiparous Holstein and four multiparous Brown Swiss cows that were distributed into four groups and arranged in a randomized complete block design with four 4-wk periods. The four treatments included a control diet of a 50:50 ratio of forage-to-concentrate; a fish oil diet of the control diet with 2% (on dry matter basis) added fat from menhaden fish oil; a fish oil with extruded soybean diet of the control diet with 1% (on dry matter basis) added fat from menhaden fish oil and 1% (on dry matter basis) added fat from extruded soybeans; and an extruded soybean diet of the control diet with 2% (on dry matter basis) added fat from extruded soybeans. Milk from cows fed control, fish oil, fish oil with extruded soybean, and extruded soybean diets contained 3.31, 2.58, 2.94, and 3.47% fat, respectively. Concentrations of conjugated linoleic acid in milk were highest in the fish oil (2.30 g/100 g of fatty acids) and fish oil with extruded soybean (2.17 g/100 g of fatty acids) diets compared with the control (0.56 g/100 g fatty acids) diet. Milk, cream, butter, and buttermilk from the fish oil, fish oil with extruded soybean, and extruded soybean diets had higher concentrations of transvaccenic acid and unsaturated fatty acids compared with the controls. Butter made from the extruded soybean diet was softest compared with all treatments. An experienced sensory panel found no flavor differences in milks or butters.

Increase in the intensity of thermoluminescence Q-band during leaf ageing is due to a block in the electron transfer from Q( A) to Q( B).

The thermoluminescence (TL) parameters in intact leaves and thylakoids isolated from leaves showed a different pattern of change during leaf ageing. Ageing of leaves brought about a decrease in the B-band and a simultaneous increase in the Q-band. Thylakoids showed only a decrease in the B-band. The TL bands further show that there is generation of an endogenous electron transport inhibitor during leaf ageing.

Short communication: Consumer evaluation of milk high in conjugated linoleic acid.

A consumer evaluation was undertaken to determine whether there were differences in the acceptability of milk from cows fed a control or a fish oil diet. The two treatments included a control diet of a 50:50 ratio of forage-to-concentrate and fish oil added to the control diet with 2% (on dry matter basis) added fat from menhaden fish oil. Milk from cows fed the control or fish oil diet contained 3.31 and 2.58% fat and 0.56 and 2.30 g of total conjugated linoleic acid/100 g of fatty acids, respectively. Consumer evaluation of control and fish oil milks found no difference in acceptability.