Who Benefited Most from the Internet-Based Conversational Engagement RCT (I-CONECT)? Application of the Personalized Medicine Approach to a Behavioral Intervention Study.

BACKGROUND: Many Alzheimer's Disease (AD) clinical trials have failed to demonstrate treatment efficacy on cognition. It is conceivable that a complex disease like AD may not have the same treatment effect due to many heterogeneities of disease processes and individual traits. OBJECTIVES: We employed an individual-level treatment response (ITR) approach to determine the characteristics of treatment responders and estimated time saved in cognitive decline using the Internet-based Conversational Engagement Clinical Trial (I-CONECT) behavioral intervention study as a model. DESIGN AND SETTING: I-CONECT is a multi-site, single-blind, randomized controlled trial aimed to improve cognitive functions through frequent conversational interactions via internet/webcam. The experimental group engaged in video chats with study staff 4 times/week for 6 months; the control group received weekly 10-minute check-in phone calls. PARTICIPANTS: Out of 186 randomized participants, current study used 139 participants with complete information on both baseline and 6-month follow-up (73 with mild cognitive impairment (MCI), 66 with normal cognition; 64 in the experimental group, and 75 in the control group). MEASUREMENTS: ITR scores were generated for the Montreal Cognitive Assessment (MoCA) (global cognition, primary outcome) and Category Fluency Animals (CFA) (semantic fluency, secondary outcome) that showed significant efficacy in the trial. ITR scores were generated through 300 iterations of 3-fold cross-validated random forest models. The average treatment difference (ATD) curve and the area between the curves (ABC) were estimated to measure the heterogeneity of treatment responses. Responder traits were identified using SHapley Additive exPlanations (SHAP) and decision tree models. The time saved in cognitive decline was explored to gauge clinical meaningfulness. RESULTS: ABC statistics showed substantial heterogeneity in treatment response with MoCA but modest heterogeneity in treatment response with CFA. Age, cognitive status, time spent with family and friends, education, and personality were important characteristics that influenced treatment responses. Intervention group participants in the upper 30% of ITR scores demonstrated potential delays of 3 months in semantic fluency (CFA) and 6 months in global cognition (MoCA), assuming a 5-fold faster natural cognitive decline compared to the control group during the post-treatment period. CONCLUSIONS: ITR-based analyses are valuable in profiling treatment responders for features that can inform future trial design and clinical practice. Reliably measuring time saved in cognitive decline is an area of ongoing research to gain insight into the clinical meaningfulness of treatment.

Probiotic potential of a novel endophytic Streptomyces griseorubens CIBA-NS1 isolated from Salicornia sp. against Vibrio campbellii infection in shrimp.

A novel endophytic Streptomyces griseorubens CIBA-NS1 was isolated from a salt marsh plant Salicornia sp. The antagonistic effect of S. griseorubens against Vibrio campbellii, was studied both in vitro and in vivo. The strain was validated for its endophytic nature and characterized through scanning electron microscopy, morphological and biochemical studies and 16SrDNA sequencing. The salinity tolerance experiment has shown that highest antibacterial activity was at 40‰ (16 ± 1.4 mm) and lowest was at 10 ‰ salinity (6.94 ± 0.51 mm). In vivo exclusion of Vibrio by S. griseorubens CIBA-NS1 was studied in Penaeus indicus post larvae and evaluated for its ability to improve growth and survival of P. indicus. After 20 days administration of S. griseorubens CIBA-NS1, shrimps were challenged with V. campbellii. The S. griseorubens CIBA-NS1 reduced Vibrio population in test group when compared to control, improved survival (60.5 ± 6.4%) and growth, as indicated by weight gain (1.8 ± 0.05g). In control group survival and growth were 48.4 ± 3.5% and 1.4 ± 0.03 g respectively. On challenge with V. campbellii, the S. griseorubens CIBA-NS1 administered group showed better survival (85.6 ± 10%) than positive control (64.3 ± 10%). The results suggested that S. griseorubens CIBA-NS1 is antagonistic to V. campbellii, reduce Vibrio population in the culture system and improve growth and survival. This is the first report on antagonistic activity of S. griseorubens isolated from salt marsh plant Salicornia sp, as a probiotic candidate to prevent V. campbellii infection in shrimps.

Jute fibre reinforced biodegradable composites using starch as a biological macromolecule: Fabrication and performance evaluation.

The aim of this study is to develop environment friendly packaging and life style materials for replacing conventionally explored hazardous synthetic materials. The study carried out by using raw jute fibre reinforced thermoplastic corn starch (TPCS) is to develop biodegradable flexible composite materials. Flexible composites are prepared by maintaining with different fibre content (30 %, 40 % and 50 wt%). A thin coating of polyurethane based formulation is applied on one side of the developed composite to make it water resistant. Composite samples are examined in terms of their tensile properties, tear resistance, folding endurance, water absorbency, capillary action etc. The results show that flexible composites, having 50 % fibre content have tensile strength of 12.8 MPa and 12 MPa at cross and machine direction respectively compared to 3.1 MPa for the TPCS film. The Water drop test on the coated side of the developed material concluded that there is no water penetration even after 60 min of wetting. The interaction between two hydrophilic components is established with FTIR analysis. The XRD analysis was carried out to find the crystallinity of TPCS, Jute fibre and composite samples. Surface morphology and fibre/matrix interaction is observed by SEM. The detail chemical mechanism involved of fibre matrix interaction also been postulated. The scientific finding shows that the developed flexible material can be suitable for making packaging and life style items.

Frequency of Hyponatremia in Adults with Acute Bacterial Meningitis.

Bacterial meningitis is a life-threatening disease. Bacterial meningitis patients are prone to develop acute hyponatremia. In the central nervous system infection hyponatremia could be due to the Syndrome of Inappropriate Anti Diuretic Hormone secretion. The frequency of hyponatremia in adults with acute bacterial meningitis patients was seen in this study. This cross-sectional study was conducted in the Internal Medicine Department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh from February 2016 to July 2016. A total of 50 patients were enrolled in this study by purposive sampling. Among 50 acute bacterial meningitis patients, 33 (66%) were diagnosed as hyponatremic state. The mean serum sodium level of 33 hyponatremic bacterial meningitis cases was 130.66±2.95 mmol/L. Most of the cases (78.79%) were mild hyponatremic state (130 mmol/L-135 mmol/L) whereas 18.18% were revealed as moderate hyponatremia (125 mmol/L-129 mmol/L). Only 3.03% of cases were presented as severe cases (≤124 mmol/L). The result revealed that a large number of patients with acute bacterial meningitis were suffering from hyponatremia and in the majority of cases were mildly hyponatremic.

A natural sustained-intestinal release formulation of red chili pepper extracted capsaicinoids (Capsifen®) safely modulates energy balance and endurance performance: a randomized, double-blind, placebo-controlled study.

Introduction: Overweight and obesity are major public health concerns, with a sharp increase in prevalence over the last few decades. The primary cause is an imbalance between calorie intake and expenditure due to a rise in calorie-rich processed food and reduced physical activity. Energy balance in humans involves complex processes including thermogenesis, a crucial factor in regulating energy expenditure. Methods: In this randomized, double-blinded, placebo-controlled three-arm three-sequence study, we investigated the efficacy of Capsifen® (CapF), a pungency-masked sustained-intestinal release formulation of red chili extract, on energy expenditure, fat oxidation, and endurance using the Quark C-PET system in healthy overweight participants, with and without exercise. In the study, 105 healthy participants were randomized to receive either placebo, CapF 100 mg/day, or CapF 200 mg/day for 28 days. Results: CapF demonstrated a dose-dependent response to increased energy expenditure and fatty acid oxidation with a concomitant reduction in body weight. Both CapF 100 and CapF 200 also increased the time to exhaustion. Discussion: These results demonstrate the plausible efficacy of CapF in energy expenditure and physical performance in otherwise healthy adults who have a high body mass index. Clinical trial registration: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MjQzNTg=&Enc=&userName=CTRI/2018/04/013157 dated 04 October 2018.

Practices and perspectives on advanced diagnostic and interventional bronchoscopy among pediatric pulmonologists in the United States.

INTRODUCTION: Advanced diagnostic bronchoscopy includes endobronchial ultrasound (EBUS) guided transbronchial lung and lymph node biopsies, CT navigation and robotic bronchoscopy. Interventional bronchoscopy refers to procedures performed for therapeutic purposes such as balloon dilation of the airway, tissue debulking, cryotherapy, removal of foreign bodies and insertion of endobronchial valves [1]. For adult patients, these procedures are standard of care [2, 3]. Despite a lack of formalized training, there are numerous case reports and case series describing the use of advanced diagnostic and interventional bronchoscopy techniques in children. The safety and feasibility of EBUS-TBNA, cryotherapy techniques, endobronchial valves among other techniques have been demonstrated in these publications [1, 4-9]. METHODS: We sought to better understand the current practices and perspectives on interventional and advanced bronchoscopy among pediatric pulmonologists through surveys sent to pediatric teaching hospitals across the United States. RESULTS: We received 43 responses representing 28 programs from 25 states. The highest bronchoscopy procedure volume occurred in the 0-5 years age group. Among our respondents, 31% self-identified as a pediatric interventional/advanced bronchoscopist. 79% believe that advanced and interventional training is feasible in pediatric pulmonology and 77% believe it should be offered to pediatric pulmonary fellows. DISCUSSION: This is the first study to characterize current practices and perspectives regarding advanced diagnostic and interventional bronchoscopy procedures among pediatric pulmonologists in the United States. Pediatric interventional pulmonology (IP) is in its infancy and its beginnings echo those of the adult IP where only certain centers were performing these procedures.

Primary preputial reconstruction following surgical excision of cutaneous mast cell tumours without penile amputation in eight dogs.

CASE HISTORY: Medical records from a single referral hospital (Davies Veterinary Specialists, Hitchin, UK) were reviewed to identify dogs (n = 8) with preputial cutaneous mast cell tumours (CMCT) that underwent surgical excision and primary preputial reconstruction, preserving the penis and urethra, after clients declined alternatives such as penile amputation and urethrostomy, from June 2017-June 2022. CLINICAL FINDINGS: Tumours had a median diameter of 21.5 (min 15, max 30) mm, were located cranioventrally (3/8), caudoventrally (1/8), laterally (2/8) and dorsally (2/8) relative to the prepuce and were diagnosed as CMCT based on cytology. No dogs had hepatic or splenic metastasis on cytology but inguinal lymph node metastasis was identified in 3/4 dogs sampled. TREATMENT AND OUTCOME: The owners of all dogs had declined penile amputation and scrotal urethrostomy. The CMCT were excised and primary reconstruction of the prepuce performed. Surgical lateral margins of 10, 20 or 30 mm were used and the deep margin excised the inner preputial lamina or underlying muscular fascia. The deep margin for caudoventral CMCT involved excision of the underlying SC adipose tissue. Preputial advancement was performed in 3/8 dogs to achieve adequate penile coverage. Histopathology confirmed all CMCT were Kiupel low grade, Patnaik grade II with complete margins in 6/8 dogs but identified metastasis only in one inguinal lymph node from one dog. Two dogs encountered minor complications (infection and a minor dehiscence) and one dog had a major complication (infection with major dehiscence). Median follow-up duration was 125 weeks, excluding one dog with 4 weeks of follow-up. None of the dogs experienced local recurrence or died of mast cell disease during the available follow-up period. CLINICAL RELEVANCE:  This clinical study evaluated a surgical alternative to penile amputation and advanced reconstructive techniques for Kuipel low/Patnaik grade II preputial CMCT when these procedures were declined by owners. Surgical excision of preputial CMCT with lateral margins of 10, 20 or 30 mm with primary preputial reconstruction is achievable with low morbidity and a good outcome when penile amputation and scrotal urethrostomy is not an option.

Corrigendum: Exploring the short-term influence of a proprietary oil extract of black cumin (Nigella sativa) on non-restorative sleep: a randomized, double-blinded, placebo-controlled actigraphy study.

[This corrects the article DOI: 10.3389/fnut.2023.1200118.].

Assessment of Dialysis Adequacy Using Small Solute Clearance Indices among Twice versus Thrice Weekly Maintenance Hemodialysis Patients in a Tertiary Care Hospital of Bangladesh.

This observational study was carried out in the Department of Nephrology, Mymensingh Medical College Hospital, Bangladesh from January 2020 to December 2020. A total of 179 patients were included in this study according to inclusion and exclusion criteria. Informed written consent was taken from each patient. All patients were underwent detail history taking, thorough physical examination and relevant investigations. Data collection was conducted through a structured questionnaire. Collected data were analyzed using the statistical software SPSS 23.0. Mean age ±SD of the study patients was 47.06±14.1 with a majority in age group 41-50 years. Male predominance was observed with a male: female ratio of 2.19:1 and 68.7% male patients. Level of pre-dialysis, post-dialysis urea in the study population was 123.77±26.86mg/dl, 50.27±15.70mg/dl respectively and mean ±SD of Urea Reduction Ratio (URR) in hemodialysis (target >65.0%) was 67.2±1.9. Most of the 8 hours (two times) per week hemolysis patients could not achieve the target value of dialysis adequacy parameters. On the other hand, maximum people in 12 hours (three times) per week hemodialysis group achieved the target value of dialysis adequacy parameters. It is important to calculate Kt/V or URR and individualize the dialysis doses for each patient.

Expert panel recommendations for topical hemostatic agent use in varied bleeding sites and situations during neuro-spine surgeries.

Intraoperative bleeding poses a substantial challenge, particularly in neuro-spine surgeries leading to complications such as hematomas, infections, and hemodynamic instability. Despite their proven efficacy, use of topical hemostatic agents (THAs) lacks comprehensive published literature and guidelines particularly in the Indian setting. The present study provides the first-ever Indian expert panel recommendations for effective adjunct THA use in different intraoperative bleeding sites and situations in neuro-spine surgeries. A comprehensive approach, encompassing a literature review, followed by experience sharing in a meeting using a survey helped integrate expert opinions in the form of practical algorithms to guide THA selection. Our survey results revealed a strong inclination towards specific THAs, flowable gelatin + thrombin being choice of THA for difficult to access and problematic bleeding situations during tumor removal/resection, transsphenoidal hypophysectomy and skull-based procedures. Both oxidized regenerated cellulose (ORC)/Fibrillar and flowable gelatin + thrombin were recommended for continuous oozing. ORC/Fibrillar was preferred for arteriovenous and cavernous malformations. This expert-panel guidance on THA use aims to optimize hemostat use practices and improve surgical outcomes in neuro-spine surgery.

Surgical treatment of canine urethral prolapse via urethropexy or resection and anastomosis.

OBJECTIVES: The objective was to report and compare the complications and recurrence rates of urethral prolapse in dogs when treated with urethropexy, resection and anastomosis or a combined surgical technique. STUDY DESIGN: Retrospective study. MATERIALS AND METHODS: A total of 86 dogs were identified from the medical records of 10 veterinary referral hospitals from February 2012 and October 2022. Dogs were included if they underwent surgery for a urethral prolapse at first presentation. Complications were classified as minor or major based on the necessity of further surgical intervention. Complications leading to death were also considered major complications. RESULTS: Seventy-nine dogs were included, urethropexy (n=44), resection and anastomosis (n=27) and a combined surgical technique (n=8). Minor complications were identified in 41 of 79 dogs (51.9%): urethropexy 19 of 44 (43.2%), resection and anastomosis 18 of 27 (66.6%) and a combined surgical technique four of eight (50%). Major complications occurred in 23 dogs (29.1%), of which 21 were recurrence (26.6%). Recurrence occurred in 17 of 44 dogs following a urethropexy (38.6%), three of 27 dogs following resection and anastomosis (11.1%) and one of eight dogs treated with a combined surgical technique (12.5%). Recurrence of a urethral prolapse was significantly more likely following urethropexy in comparison to resection and anastomosis. CLINICAL SIGNIFICANCE: Resection and anastomosis was associated with a lower recurrence rate in comparison to urethropexy for the surgical treatment of urethral prolapse. Based on these results, we concluded that resection and anastomosis may be preferable to urethropexy for treatment of urethral prolapse at first presentation. Urethropexy, and resection and anastomosis combined surgical technique was associated with low recurrence rate; however, further studies will be needed to clarify if it provides any benefit over resection and anastomosis.

First Simultaneous Determination of Inclusive and Exclusive |V_{ub}|.

The first simultaneous determination of the absolute value of the Cabibbo-Kobayashi-Maskawa matrix element V_{ub} using inclusive and exclusive decays is performed with the full Belle data set at the ϒ(4S) resonance, corresponding to an integrated luminosity of 711 fb^{-1}. We analyze collision events in which one B meson is fully reconstructed in hadronic modes. This allows for the reconstruction of the hadronic X_{u} system of the semileptonic b→uℓν[over ¯]_{ℓ} decay. We separate exclusive B→πℓν[over ¯]_{ℓ} decays from other inclusive B→X_{u}ℓν[over ¯]_{ℓ} and backgrounds with a two-dimensional fit that utilizes the number of charged pions in the X_{u} system and the four-momentum transfer q^{2} between the B and X_{u} systems. Combining our measurement with information from lattice QCD and QCD calculations of the inclusive partial rate as well as external experimental information on the shape of the B→πℓν[over ¯]_{ℓ} form factor, we determine |V_{ub}^{excl}|=(3.78±0.23±0.16±0.14)×10^{-3} and |V_{ub}^{incl}|=(3.88±0.20±0.31±0.09)×10^{-3}, respectively, with the uncertainties being the statistical error, systematic errors, and theory errors. The ratio of |V_{ub}^{excl}|/|V_{ub}^{incl}|=0.97±0.12 is compatible with unity.

Search for a Heavy Neutrino in τ Decays at Belle.

We report on a search for a heavy Majorana neutrino in the decays τ^{-}→π^{-}ν_{h}, ν_{h}→π^{±}ℓ^{∓}, ℓ=e, µ. The results are obtained using the full data sample of 988 fb^{-1} collected with the Belle detector at the KEKB asymmetric energy e^{+}e^{-} collider, which contains 912×10^{6} ττ pairs. We observe no significant signal and set 95% CL upper limits on the couplings of the heavy right-handed neutrinos to the conventional standard model left-handed neutrinos in the mass range 0.2-1.6 GeV/c^{2}. This is the first study of a mixed couplings of heavy neutrinos to τ leptons and light-flavor leptons.

Classification of Osteoporosis.

Osteoporosis is defined by low bone quality, strength and increased fracture risk. Primary and secondary osteoporosis are the two forms of osteoporosis classified on the basis of factors affecting the metabolism of bone. Primary osteoporosis develops as a result of aging or menopause-related bone demineralization. Type I/postmenopausal and type II/senile osteoporosis are two subtypes of primary osteoporosis. Secondary osteoporosis is due to pathological conditions and medications other than aging and menopause that lead to deprivation of bone mass and elevated fracture risk. Classification of osteoporosis based on BMD testing with DEXA devised by the World Health Organization utilizes T-score in BMD reporting of women in menopausal transition or postmenopause and men ≥ 50 years. Z-scores are preferred, while BMD reporting in premenopausal women, adults < 50 years of age, and children. BMD alone is not diagnostic of osteoporosis in men < 50 years. The Fracture Risk Assessment Tool Model (FRAX) is a software algorithm that incorporates significant predictors of fracture risk and BMD in individuals to predict the risk of fracture. FRAX predicts the "10-year probability of a major fracture (hip, clinical spine, humerus, or wrist fracture) and the 10-year probability of a hip fracture".

Bone marrow transplant: A two-decade single centre hematology experience.

Background: Bone Marrow Transplant (BMT) is a curative form of therapy for many hematological disorders in both the adult and pediatric patients. The availability of BMT in the AFMS at AHRR for the last 02 decades has been a game changer for the patients. Methods: We reviewed our BMT data since the inception of the program till Feb 2023. Results: Over 700 patients with more than 23 different types of hematological disorders have undergone this procedure 58%% patients underwent an Autologous BMT and 42% an allogenic BMT. Autologous BMT for Multiple Myeloma and Allogenic BMT for Aplastic Anemia and Acute Leukemias have been the most common indications. 73% patients were adults, and 27% patients were of the pediatric age group. The male: female ratio was 2:1. The spectrum of allogenic Hematopoietic Stem Cell Transplant (HSCT) has expanded from Matched Sibling Donor (MSD) transplants to Matched Unrelated Donor (MUD) Transplants and Haploidentical Donor Transplants. 93% of our Allogenic BMT patients underwent a MSD BMT, 1% MUD BMT and 06% Haploidentical BMT. Today no patient with a malignant hematological disorder requiring a BMT is denied the procedure due to the lack of an HLA donor due to the availability of haploidentical BMT. Conclusion: The evolution of a BMT program has a long learning curve and the expanded pool of eligible donors has led to a situation of "transplant for all". Haploidentical HSCT for nonmalignant hematological disorders is an unmet need. CART cell therapy and Cellular therapies need to be prioritized for future inclusion.

First Measurement of the Nuclear-Recoil Ionization Yield in Silicon at 100 eV.

We measured the nuclear-recoil ionization yield in silicon with a cryogenic phonon-sensitive gram-scale detector. Neutrons from a monoenergetic beam scatter off of the silicon nuclei at angles corresponding to energy depositions from 4 keV down to 100 eV, the lowest energy probed so far. The results show no sign of an ionization production threshold above 100 eV. These results call for further investigation of the ionization yield theory and a comprehensive determination of the detector response function at energies below the keV scale.

Are the Cytotoxic Properties of Conjugated Unsaturated Ketones Inactivated by Thiols?

The focus of this study was to examine whether the conversion of cytotoxic conjugated unsaturated ketones (or enones) into the corresponding thiol adducts leads to a reduction or abolition of cytotoxic potencies. A number of enones and related thiol adducts were evaluated against human HCT116 and HT29 colon cancer cells. Some 63% of the IC50 values are less than 10 µM and several compounds are more toxic than 5-FU. The thiol adducts are either more potent or are equipotent with the corresponding enones. A number of compounds are far more toxic to HCT116 and HT29 neoplasms than non-malignant CRL1790 cells leading to impressive Selectivity Index figures. An additional positive feature of these compounds is that they have favorable ADME properties.